37 results on '"Finke, Jürgen"'
Search Results
2. Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.
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McLornan D, Szydlo R, Koster L, Chalandon Y, Robin M, Wolschke C, Beelen D, Socié G, Bornhäuser M, Angelucci E, Niederwieser D, Gerbitz A, Finke J, Vitek A, Itälä-Remes M, Radujkovic A, Kanz L, Potter V, Chevallier P, Stelljes M, Petersen E, Robinson S, Poiré X, Klyuchnikov E, Hernández-Boluda JC, Czerw T, Hayden P, Kröger N, and Yakoub-Agha I
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- Adolescent, Adult, Aged, Allografts, Chronic Disease, Disease-Free Survival, Europe, Female, Humans, Male, Middle Aged, Retrospective Studies, Societies, Medical, Survival Rate, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy, Transplantation Conditioning
- Abstract
This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 10
9 /L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P = .10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P = .08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P = .78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P = .001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. All rights reserved.)- Published
- 2019
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3. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Shimoni A, Labopin M, Savani B, Byrne M, Volin L, Finke J, Niederwieser D, Ehninger G, Blaise D, Beelen D, Tabrizi R, Sengeloev H, Ganser A, Cornelissen JJ, Mohty M, and Nagler A
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- Aged, Disease-Free Survival, Europe epidemiology, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Humans, Male, Middle Aged, Retrospective Studies, Societies, Medical, Survival Rate, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Siblings, Transplantation Conditioning, Unrelated Donors
- Abstract
Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P = .005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P < .001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P = .78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P = .30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P = .0001) or CR2 (HR, 1.51; P = .02) compared with CR1, female recipients (HR, 0.71; P = .006), adverse cytogenetics (HR, 2.52; P = .01), and prior graft-versus-host disease (HR, 1.31; P = .04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P = .97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P = .15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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4. Allogeneic Stem Cell Transplantation for Blast Crisis Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: A Retrospective Study by the EBMT Chronic Malignancies Working Party.
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Radujkovic A, Dietrich S, Blok HJ, Nagler A, Ayuk F, Finke J, Tischer J, Mayer J, Koc Y, Sorà F, Passweg J, Byrne JL, Jindra P, Veelken JH, Socié G, Maertens J, Schaap N, Stadler M, Itälä-Remes M, Tholouli E, Arat M, Rocha V, Ljungman P, Yakoub-Agha I, Kröger N, and Chalandon Y
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- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Prognosis, Protein Kinase Inhibitors pharmacology, Retrospective Studies, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Protein Kinase Inhibitors therapeutic use, Transplantation Conditioning methods
- Abstract
The prognosis of patients with blast crisis (BC) chronic myeloid leukemia (CML) is still dismal. Allogeneic stem cell transplantation represents the only curative treatment option, but data on transplant outcomes are scarce. We therefore conducted a retrospective, registry-based study of adult patients allografted for BC CML, focusing on patients with active disease at transplant and pretransplant prognostic factors. One hundred seventy patients allografted for BC CML after tyrosine kinase inhibitor pretreatment between 2004 and 2016 were analyzed. Before transplant, 95 patients were in remission, whereas 75 patients had active BC. In multivariable analysis of the entire cohort, active BC at transplant was the strongest factor associated with decreased overall survival (hazrd ratio, 1.87; P = .010) and shorter leukemia-free survival (LFS; hazard ratio, 1.69; P = .017). For patients with BC in remission at transplant, advanced age (≥45 years), lower performance status (≤80%), longer interval from diagnosis BC to transplant (>12 months), myeloablative conditioning, and unrelated donor (UD) transplant were risk factors for inferior survival. In patients with active BC, only UD transplant was significantly associated with prolonged LFS and trended toward improved overall survival. In summary, survival of patients allografted for BC CML was strongly dependent on pretransplant remission status. In patients with remission of BC, conventional prognostic factors remained the major determinants of outcome, whereas in those with active BC at transplant, UD transplant was associated with prolonged LFS in our study., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2019
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5. Unmanipulated haploidentical versus HLA-matched sibling allogeneic hematopoietic stem cell transplantation in relapsed/refractory acute myeloid leukemia: a retrospective study on behalf of the ALWP of the EBMT.
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Battipaglia G, Boumendil A, Labopin M, Ciceri F, Tischer J, Stelljes M, Ehninger G, Beelen D, Finke J, Van Lint MT, Eder M, Afanasyev B, Fanin R, Mohty M, Ruggeri A, and Nagler A
- Subjects
- Adolescent, Adult, Aged, Allografts, Disease-Free Survival, Female, HLA Antigens, Humans, Male, Middle Aged, Registries, Retrospective Studies, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation, Histocompatibility Testing, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Siblings, Transplantation Conditioning
- Abstract
Refractory or relapsed acute myeloid leukemia (R/R-AML) has poor prognosis. Allogeneic hematopoietic stem-cell transplantation (HSCT) may provide cure in this scenario. We compared outcomes of HSCT from HLA-identical (HLA-id, n = 1654) sibling or haploidentical (Haplo, n = 389) donors in patients with R/R-AML, performed during the period 2007-2015. The Haplo group included patients receiving an unmanipulated graft (post-transplant cyclophosphamide, n = 278; in vivo T-cell depletion, n = 95; or both, n = 16). Median age at HSCT was 52 (range 18-74) years. Median follow-up was 16 and 22 months for HLA-id sibling and Haplo recipients, respectively (p = 0.11). Compared to MSD, Haplo HSCT were performed more recently (2013 vs 2011, p < 0.01), at longer interval from diagnosis (7 vs 5 months, p < 0.01), more frequently using bone marrow as stem cell source (47% vs 8%, p < 0.01) and with a reduced intensity conditioning regimen (50% vs 43%, p = 0.03). Engraftment was higher (93% vs 83%, p < 0.01) in HLA-id sibling. In multivariate analysis, Haplo HSCT was associated with lower GVHD/relapse-free survival, inferior LFS and OS and higher NRM, mainly due to a higher rate of infections (41% vs 25%, p < 0.01). For R/R-AML, HLA-id sibling donors remain the gold standard, when available, due to higher mortality in Haplo without significant gain in disease control.
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- 2019
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6. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation.
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Nagler A, Labopin M, Dholaria B, Finke J, Brecht A, Schanz U, Niittyvuopio R, Neubauer A, Bornhäuser M, Santarone S, Beelen D, Shimoni A, Rösler W, Giebel S, Savani BN, and Mohty M
- Subjects
- Adolescent, Adult, Aged, Europe, Female, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Retrospective Studies, Surveys and Questionnaires, Survival Rate, Young Adult, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Although second allogeneic haematopoietic cell transplantation (allo-HCT2) is a therapeutic option for patients relapsing after first HCT (allo-HCT1), there is limited data on allo-HCT2 in patients with acute lymphoblastic leukaemia (ALL). We retrospectively studied 245 patients receiving allo-HCT2 as a salvage treatment for relapse following allo-HCT1 between the 2000 and 2017. The median age at allo-HCT2 was 34·6 years (range: 18-74). One hundred and one patients (41%) received sibling donor and 144 (59%) unrelated donor allo-HCT2. Acute graft-versus-host disease (GVHD) grade II-IV and III-IV occurred in 33% and 17% of the patients, respectively. The incidence of 2-year total and extensive chronic GVHD was 38% and 19%, respectively. The 2- and 5-year cumulative incidence of non-relapse mortality, relapse incidence, leukaemia-free survival, overall survival and GVHD-free, relapse-free survival (GRFS) were 24% and 26%, 56% and 62%, 20% and 12%, 30% and 14% and 12% & 7%, respectively. In multivariate analysis, factors associated with overall survival were age, time from allo-HCT1 to relapse, conditioning for allo-HCT1, Karnofsky score at allo-HCT2 and donor type for allo-HCT2. In conclusion, outcomes of allo-HCT2 in ALL patients were poor, with only 14% overall survival and 7% GRFS at 5 years with very high relapse incidence., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2019
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7. Comparative outcomes of myeloablative and reduced-intensity conditioning allogeneic hematopoietic cell transplantation for therapy-related acute myeloid leukemia with prior solid tumor: A report from the acute leukemia working party of the European society for blood and bone marrow transplantation.
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Lee CJ, Labopin M, Beelen D, Finke J, Blaise D, Ganser A, Itälä-Remes M, Chevallier P, Labussière-Wallet H, Maertens J, Yakoub-Agha I, Bourhis JH, Mailhol A, Mohty M, Savani BN, and Nagler A
- Subjects
- Adult, Aged, Bone Marrow Transplantation, Disease-Free Survival, Europe, Female, Humans, Male, Middle Aged, Societies, Medical, Survival Rate, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute microbiology, Leukemia, Myeloid, Acute therapy, Neoplasms, Second Primary mortality, Neoplasms, Second Primary therapy, Transplantation Conditioning
- Abstract
Therapy-related acute myeloid leukemia (t-AML) arises as a late complication following antecedent solid tumors or hematologic diseases and their associated treatments. There are limited data regarding risk factors and outcomes following allogeneic hematopoietic cell transplantation (HCT) for t-AML following a prior solid tumor, and furthermore, the impact of myeloablative (MAC) vs reduced-intensity conditioning (RIC) on survival is unknown. The acute leukemia working party (ALWP) of the European society for blood and bone marrow transplantation (EBMT) performed a large registry study that included 535 patients with t-AML and prior solid tumor who underwent first MAC or RIC allogeneic HCT from 2000-2016. The primary endpoints of the study were OS and LFS. Patients receiving RIC regimens had an increase in relapse incidence (hazard ratio [HR], 1.52; 95% confidence interval [CI] 1.02-2.26; P = 0.04), lower LFS (HR, 1.52; 95% CI 1.12-2.05, P = 0.007), and OS (HR, 1.51; CI 1.09-2.09; P = 0.012). There were no differences in NRM and GRFS. Importantly, LFS and OS were superior in patients receiving ablative regimens due to a decrease in relapse. As NRM continues to decline in the current era, it is conceivable that outcomes of HCT for t-AML with prior solid tumor may be improved by careful patient selection for myeloablative regimens., (© 2018 Wiley Periodicals, Inc.)
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- 2019
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8. Impact of Lung Function on Bronchiolitis Obliterans Syndrome and Outcome after Allogeneic Hematopoietic Cell Transplantation with Reduced-Intensity Conditioning.
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Duque-Afonso J, Ihorst G, Waterhouse M, Zeiser R, Wäsch R, Bertz H, Müller-Quernheim J, Finke J, Marks R, and Prasse A
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- Adult, Aged, Bronchiolitis Obliterans pathology, Female, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Risk Factors, Treatment Outcome, Young Adult, Bronchiolitis Obliterans diagnosis, Hematopoietic Stem Cell Transplantation methods, Lung pathology, Lung Diseases etiology, Transplantation Conditioning methods
- Abstract
Lung function deterioration contributes to treatment-related morbidity and mortality in patients after allogeneic hematopoietic cell transplantation (allo-HCT). Better understanding of impaired lung function including bronchiolitis obliterans syndrome (BOS) as chronic manifestation of graft-versus-host disease (GVHD) might improve outcomes of patients after allo-HCT. To detect early pulmonary function test abnormalities associated with BOS incidence and outcome after allo-HCT, we performed a retrospective analysis of homogenous-treated 445 patients (median age, 61.9 years; range, 19 to 76 years) with a reduced intensity/toxicity conditioning protocol. The cumulative incidence of BOS was 4.1% (95% confidence interval [CI], 2.6 to 6.4) at 1 year and 8.6% (95% CI, 6.3 to 11.6) at 5 years after allo-HCT with a median follow-up of 43.2 months (range, 3.3 to 209 months). In multivariate analysis, pre-existence of moderate small airway disease reflected by decreased midexpiratory flows before allo-HCT was associated with increased risk for BOS development. In addition, severe small airway disease before allo-HCT and combined restrictive/obstructive lung disease at day +100 after allo-HCT were associated with higher risk for nonrelapse mortality (NRM) due mainly to pulmonary cause of death. In summary, we identified novel pulmonary function test abnormalities prior and after allo-HCT associated with BOS development and NRM. These findings might help to identify a risk population and result in personalized GVHD prophylaxis and preventive or early therapeutic interventions., (Copyright © 2018. Published by Elsevier Inc.)
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- 2018
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9. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study.
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Sengsayadeth S, Gatwood KS, Boumendil A, Labopin M, Finke J, Ganser A, Stelljes M, Ehninger G, Beelen D, Niederwieser D, Blaise D, Dreger P, Mufti G, Chevallier P, Mailhol A, Gilleece MH, Gorin N, Esteve J, Ciceri F, Baron F, Schmid C, Giebel S, Mohty M, Savani BN, and Nagler A
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- Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Registries, Retrospective Studies, Survival Rate, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Neoplasms, Second Primary mortality, Neoplasms, Second Primary therapy, Transplantation Conditioning
- Abstract
Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML., (© 2018 by The American Society of Hematology.)
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- 2018
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10. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study.
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Sengsayadeth S, Labopin M, Boumendil A, Finke J, Ganser A, Stelljes M, Ehninger G, Beelen D, Niederwieser D, Blaise D, Dreger P, Mufti G, Chevallier P, Mailhol A, Gatwood KS, Gorin N, Esteve J, Ciceri F, Baron F, Schmid C, Giebel S, Mohty M, Savani BN, and Nagler A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Europe, Female, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Treatment Outcome, Young Adult, Bone Marrow Transplantation methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods
- Abstract
Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [CI], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% CI, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1.341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (≤80%), ex vivo T cell depletion, other malignant hematologic diseases, and patient cytomegalovirus seropositivity were associated with inferior OS and LFS. These variables should be considered in patients with sAML in need of HCT, and further study regarding the impact of conditioning regimens on relapse is needed., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
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- 2018
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11. Cyclophosphamide versus etoposide in combination with total body irradiation as conditioning regimen for adult patients with Ph-negative acute lymphoblastic leukemia undergoing allogeneic stem cell transplant: On behalf of the ALWP of the European Society for Blood and Marrow Transplantation.
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Czyz A, Labopin M, Giebel S, Socié G, Apperley J, Volin L, Reményi P, Yakoub-Agha I, Orchard K, Michallet M, Stuhler G, Chaganti S, Murray M, Aljurf M, Bloor A, Passweg J, Finke J, Mohty M, and Nagler A
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- Adult, Female, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Transplantation, Homologous, Cyclophosphamide therapeutic use, Etoposide therapeutic use, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning methods, Whole-Body Irradiation methods
- Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) with myeloablative conditioning based on total body irradiation (TBI) is widely used for the treatment of adults with acute lymphoblastic leukemia (ALL). TBI is most frequently administered in combination with either cyclophosphamide (Cy/TBI) or etoposide (Vp/TBI). The goal of this study was to retrospectively compare these two regimens. Adult patients with Ph-negative ALL treated with alloHCT in first or second complete remission who received Cy/TBI (n = 1346) or Vp/TBI (n = 152) conditioning were included in the analysis. In a univariate analysis, as compared to Cy/TBI, the use of Vp/TBI was associated with reduced incidence of relapse (17% vs. 30% at 5 years, P = .007), increased rate of leukemia-free survival (60% vs. 50%, P = .04), and improved "graft versus host disease (GVHD) and relapse-free survival" (GRFS, 43% vs. 33%, P = .04). No significant effect could be observed in terms of the incidence of nonrelapse mortality or acute or chronic GVHD. In a multivariate model, the use of Vp/TBI was associated with reduced risk of relapse (HR = 0.62, P = .04) while the effect on other study end-points was not significant. In conclusion, conditioning regimen based on Vp combined with TBI appears more effective for disease control than the combination of Cy with TBI for adult patients with Ph-negative ALL treated with alloHCT., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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12. AlloHSCT for inv(3)(q21;q26)/t(3;3)(q21;q26) AML: a report from the acute leukemia working party of the European society for blood and marrow transplantation.
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Halaburda K, Labopin M, Houhou M, Niederwieser D, Finke J, Volin L, Maertens J, Cornelissen JJ, Milpied N, Stuhler G, Kröger N, Esteve J, Mohty M, and Nagler A
- Subjects
- Adolescent, Adult, Aged, Europe, Female, Humans, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Young Adult, Bone Marrow Transplantation methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
Acute myeloid leukemia with inv(3)(q21;q26.2)/t(3;3)(q21;q26.2) (3q26 AML) is a rare disease with poor prognosis and median survival of <1 year. To evaluate allogeneic stem cell transplantation (alloHSCT) in the treatment of 3q26 AML, we studied 98 patients reported to the European Society for Blood and Marrow Transplantation between 1995 and 2013. Majority of patients were transplanted using peripheral blood, from unrelated donors and after myeloablative conditioning. Fifty-three patients were transplanted with active disease and 45 in complete remission. After a median follow-up of 47 months, 2 year leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), and graft-versus-host disease-free, relapse-free survival (GRFS) probabilities were 20%, 26%, 64%, 16%, and 14%, respectively. Two-year LFS and OS probabilities for patients transplanted in CR vs. those transplanted in active disease were 23.8 vs. 17% (p = NS) and 34.9 vs. 18.9% (p = NS), respectively. In multivariate analysis CR was the only factor associated with a trend for better LFS (p = 0.05, HR 0.64) and OS (p = 0.06, HR 0.65). CR also significantly influenced GRFS (p = 0.01; HR 0.55) and NRM (p = 0.02; HR 0.27). The results suggest that a proportion of patients might benefit from the procedure, especially if performed in CR.
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- 2018
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13. Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party.
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Robinson SP, Boumendil A, Finel H, Peggs KS, Chevallier P, Sierra J, Finke J, Poiré X, Maillard N, Milpied N, Yakoub-Agha I, Koh M, Kröger N, Nagler A, Koc Y, Dietrich S, Montoto S, and Dreger P
- Subjects
- Adult, Aged, Hematopoietic Stem Cell Transplantation mortality, Humans, Lymphoma, Mantle-Cell mortality, Middle Aged, Recurrence, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy, Transplantation Conditioning methods
- Abstract
Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.
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- 2018
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14. Unmanipulated haploidentical in comparison with matched unrelated donor stem cell transplantation in patients 60 years and older with acute myeloid leukemia: a comparative study on behalf of the ALWP of the EBMT.
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Santoro N, Labopin M, Giannotti F, Ehninger G, Niederwieser D, Brecht A, Stelljes M, Kröger N, Einsele H, Eder M, Hallek M, Glass B, Finke J, Ciceri F, Mohty M, Ruggeri A, and Nagler A
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Leukemia, Myeloid, Acute pathology, Male, Retrospective Studies, Unrelated Donors, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods
- Abstract
Background: Acute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need., Methods: We retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years., Results: Median follow-up was 23 months. Disease status at transplant differs significantly between the two groups (p < 10
-4 ). Reduced intensity conditioning (RIC) was administrated to 73 and 77% of Haplo and MUD, respectively (p = 0.23). Stem cell source was the bone marrow (BM) in 52% of the Haplo and 6% of MUD (p < 10-4 ). Anti-thymocyte globulin (ATG) was most frequently used in MUD (p < 10-4 ) while post-Tx cyclophosphamide (PT-Cy) was given in 62% of Haplo. Engraftment was achieved in 90% of the Haplo vs 97% of MUD (p < 10-4 ). In multivariate analysis, no significant difference was found between Haplo and MUD for acute (a)graft versus host disease (GVHD) grade II-IV, relapse incidence (RI), non-relapse mortality (NRM), leukemia free survival (LFS), graft-versus-host-free-relapse free survival (GRFS), and overall survival (OS). Extensive chronic (c)GVHD was significantly higher for MUD as compared to Haplo (HR 2, p = 0.01, 95% CI 1.17-3.47). A propensity score analysis confirmed the higher risk of extensive cGVHD for MUD without differences for other outcomes., Conclusions: Allo-SCT from both Haplo and MUD are valid option for AML patients ≥ 60 years of age with similar results. Transplantation from MUD was associated with higher extensive cGVHD. Our findings suggest that Haplo is a suitable and attractive graft source for patients≥ 60 with AML in need of allo-SCT.- Published
- 2018
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15. Salvage use of allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning from unrelated donors in multiple myeloma. A study by the Plasma Cell Disorders subcommittee of the European Group for Blood and Marrow Transplant Chronic Malignancies Working Party.
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Sobh M, Michallet M, Dubois V, Iacobelli S, Koster L, Van Biezen A, Fegueux N, Tabrizi R, Finke J, El-Cheikh J, Schipperus M, Meijer E, von dem Borne P, Petersen E, Russell N, Tholouli E, Passweg J, Garban F, Maertens J, Chevalier P, Maillard N, Volin L, Francois S, Lioure B, Beguin Y, Gluckman E, Ruggeri A, Garderet L, and Kröger N
- Subjects
- Adult, Female, Graft vs Host Disease etiology, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Neoplasm Recurrence, Local, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy, Transplantation Conditioning methods, Unrelated Donors
- Published
- 2017
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16. Allogeneic Stem Cell Transplantation for Patients Age ≥ 70 Years with Myelodysplastic Syndrome: A Retrospective Study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT.
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Heidenreich S, Ziagkos D, de Wreede LC, van Biezen A, Finke J, Platzbecker U, Niederwieser D, Einsele H, Bethge W, Schleuning M, Beelen DW, Tischer J, Nagler A, Glass B, Maertens J, Yáñez L, Beguin Y, Sill H, Scheid C, Stelljes M, Ganser A, Zachée P, Selleslag D, de Witte T, Robin M, and Kröger N
- Subjects
- Aged, Cytomegalovirus immunology, Europe, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Karnofsky Performance Status, Leukemia, Myeloid, Acute mortality, Male, Myelodysplastic Syndromes mortality, Recurrence, Registries, Retrospective Studies, Survival Analysis, Tissue Donors, Transplantation Conditioning mortality, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods
- Abstract
In this retrospective analysis we evaluated the outcome of 313 patients aged ≥ 70 years in the registry of the European Group for Blood and Marrow Transplantation with myelodysplastic syndrome (MDS; n = 221) and secondary acute myeloid leukemia (n = 92) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from related (n = 79) or unrelated (n = 234) donors. Median age at HSCT was 72 years (range, 70 to 78). Conditioning regimen was nonmyeloablative (n = 54), reduced intensity (n = 207), or standard intensity (n = 52). Allogeneic HSCT for MDS patients ≥ 70 years was increasingly performed over time. Although during 2000 to 2004 only 16 patients received HSCT, during 2011 to 2013 the number of transplantations increased to 181. The cumulative incidence of nonrelapse mortality at 1 year and relapse at 3 years was 32% and 28%, respectively, with a 3-year overall survival rate of 34%. Good performance, determined by Karnofsky performance status, and recipients' seronegativity for cytomegalovirus was associated with 3-year estimated overall survival rates of 43% (P = .01) and 46% (P = .002), respectively. Conditioning intensity did not impact survival. After careful patient selection, allogeneic HSCT can be offered to patients older than 70 years with MDS., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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17. Thiotepa-based conditioning for allogeneic stem cell transplantation in acute lymphoblastic leukemia-A survey from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Eder S, Beohou E, Labopin M, Sanz J, Finke J, Arcese W, Or R, Bonifazi F, Aljurf M, Socié G, Passweg J, Giebel S, Mohty M, and Nagler A
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Agents, Alkylating administration & dosage, Disease-Free Survival, Female, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Histocompatibility immunology, Humans, Male, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Retrospective Studies, Thiotepa administration & dosage, Transplantation, Homologous, Young Adult, Antineoplastic Agents, Alkylating therapeutic use, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Thiotepa therapeutic use, Transplantation Conditioning methods
- Abstract
In this study, we analyzed a thiotepa-based conditioning regimen for allogeneic stem cell transplantation in adults with acute lymphoblastic leukemia, using the EBMT database. A total of 323 patients were identified. The median age was 43 years. Disease status at transplant was first complete remission (CR1) in 48.9%, CR2 in 21.7%, CR3 in 6.2%, while 23.2% of the patients had an active disease at the time of transplant. This was performed from a HLA-matched sibling (49.8%) or a matched-unrelated donor (51.2%). The incidence of acute graft-vs.-host disease (GvHD) (grade > II) was 26.6%, while chronic GvHD occurred in 35.9% of the patients at 1 year (24.6% with extensive disease). With a median follow-up of 16.8 months, the nonrelapse mortality was 12.4 and 25.3% at 100 days and 1 year, respectively. The relapse incidence at 1 year was 33.3% with no difference for patients in CR1 (27%). The one-year leukemia-free survival (LFS) and overall survival (OS) were 57 and 66%, respectively for the entire cohort and 50 and 66%, respectively in patients in CR1. Thiotepa/busulfan ± melphalan (n = 213) in comparison to thiotepa/other (n = 110) conditioning regimen resulted in higher relapse incidence at 1 year (34.9 vs. 30.3%, P = 0.016) and lower LFS (38.8 vs. 45.9%, P = 0.0203), while nonrelapse mortality (23.8 vs. 26.3%, n.s.) and OS (59.6 vs. 51.1%, P = 0.109) did not differ. This large study suggests that a thiotepa-based conditioning for allogeneic transplantation in acute lymphoblastic leukemia is feasible and effective, with the main outcomes being comparable to those achieved with other regimens. Am. J. Hematol. 92:18-22, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2017
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18. The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years-a report from the EBMT acute leukemia working party.
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Rubio MT, Savani BN, Labopin M, Polge E, Niederwieser D, Ganser A, Schwerdtfeger R, Ehninger G, Finke J, Renate A, Craddock C, Kröger N, Hallek M, Jindra P, Mohty M, and Nagler A
- Subjects
- Aged, Female, Graft Survival, Graft vs Host Disease etiology, Graft vs Host Disease immunology, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Remission Induction, Retrospective Studies, Survival Analysis, Hematopoietic Stem Cell Transplantation methods, Histocompatibility Testing, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods, Unrelated Donors
- Abstract
Background: Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited., Methods: We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate., Results: HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II-IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD., Conclusions: Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.
- Published
- 2016
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19. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT.
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Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, Schwerdtfeger R, Bunjes D, Glass B, Socié G, Ljungman P, Craddock C, Baron F, Ciceri F, Gorin NC, Esteve J, Schmid C, Giebel S, Mohty M, and Nagler A
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Female, Graft Survival, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Survival Analysis, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods, Unrelated Donors
- Abstract
The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being <50 years of age compared to only 30% in the reduced-intensity conditioning group (P=0.0001). Significantly, more patients had secondary acute myeloid leukemia (P=0.04) and Karnofsky Performance Status score <90% (P=0.02) in the reduced-intensity conditioning group. Patients <50 and ≥50 years were analyzed separately. On multivariate analysis and after adjusting for differences between the two groups, reduced-intensity conditioning in patients age ≥50 years was associated with higher overall survival (HR 0.78; P=0.01), leukemia-free survival (HR 0.82; P=0.05), and decreased non-relapse mortality (HR 0.73; P=0.03). Relapse incidence (HR 0.91; P=0.51) and chronic graft-versus-host disease (HR 1.31; P=0.11) were, however, not significantly different. In patients <50 years old, there were no statistically significant differences in overall survival, leukemia-free survival, relapse incidence, non-relapse mortality, and chronic graft-versus-host-disease between the groups. Our study shows no significant outcome differences in patients younger than 50 years receiving reduced-intensity vs myeloablative conditioning regimens after mismatched unrelated donor transplantation. Furthermore, the data support the superiority of reduced-intensity conditioning regimens in older adults receiving transplants from mismatched unrelated donors., (Copyright© Ferrata Storti Foundation.)
- Published
- 2016
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20. Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis.
- Author
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Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, Kyrcz-Krzemien S, Volin L, Anagnostopoulos A, Aljurf M, Beelen DW, Vigouroux S, Milpied N, Suarez F, and Mohty M
- Subjects
- Administration, Intravenous, Adolescent, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation, Humans, Male, Middle Aged, Registries, Retrospective Studies, Treatment Outcome, Young Adult, Busulfan therapeutic use, Cyclophosphamide therapeutic use, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning, Whole-Body Irradiation
- Abstract
Background: Cyclophosphamide plus intravenous busulfan has not been compared with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). We aimed to assess whether survival of patients receiving ablative intravenous busulfan-based conditioning regimens before a related or volunteer-unrelated donor HCT for refractory acute myeloid leukaemia is not inferior to that of patients receiving an ablative TBI-based regimen., Methods: In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. Data was obtained from the European Group for Blood and Marrow Transplantation registry. The primary endpoints of the study were overall survival and leukaemia-free survival., Findings: We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20% [range 5-100; IQR 10-32] in the intravenous busulfan plus cyclophosphamide group vs 16% [5-95; 9-33] in the cyclophosphamide plus TBI group; p=0·16). Overall survival at 2 years did not differ between the groups in the univariate analysis (31·2% [95% CI 26·8-35·5] with intravenous busulfan plus cyclophosphamide vs 33·4% [28·1-38·7] wth cyclophosphamide plus TBI; p=0·65). Leukaemia-free survival at 2 years also did not differ between groups (25·0% [95% CI 21·0-29·0] vs 28·4% [23·4-33·5]; p=0·47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0·99 [95% CI 0·83-1·20]; p=0·95) or leukaemia-free survival (HR 0·97 [0·81-1·16]; p=0·71). Main causes of non-relapse mortality were graft-versus-host disease (49 [10%] in the intravenous busulfan plus cyclophosphamide group vs 25 [7%] in the cyclophosphamide plus TBI group) and infection (36 [7%] vs 18 [5%])., Interpretation: From a practical standpoint, the use of intravenous busulfan plus cyclophosphamide is likely to be a valid and efficient alternative to cyclophosphamide plus TBI conditioning regimen for patients with refractory acute myeloid leukaemia, especially for those transplant centres without access to radiation facilities., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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21. Comparison of unrelated cord blood and peripheral blood stem cell transplantation in adults with myelodysplastic syndrome after reduced-intensity conditioning regimen: a collaborative study from Eurocord (Cord blood Committee of Cellular Therapy & Immunobiology Working Party of EBMT) and Chronic Malignancies Working Party.
- Author
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Robin M, Ruggeri A, Labopin M, Niederwieser D, Tabrizi R, Sanz G, Bourhis JH, van Biezen A, Koenecke C, Blaise D, Tischer J, Craddock C, Maillard N, Mohty M, Russel N, Schetelig J, Finke J, Gluckman E, de Witte TM, Rocha V, and Kroger N
- Subjects
- Acute Disease, Adult, Aged, Allografts, Disease-Free Survival, Europe, Female, Humans, Male, Middle Aged, Survival Rate, Cord Blood Stem Cell Transplantation, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Peripheral Blood Stem Cell Transplantation, Transplantation Conditioning, Unrelated Donors
- Abstract
Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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22. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood.
- Author
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Rodrigues CA, Rocha V, Dreger P, Brunstein C, Sengeloev H, Finke J, Mohty M, Rio B, Petersen E, Guilhot F, Niederwieser D, Cornelissen JJ, Jindra P, Nagler A, Fegueux N, Schoemans H, Robinson S, Ruggeri A, Gluckman E, Canals C, and Sureda A
- Subjects
- Adolescent, Adult, Aged, Disease-Free Survival, Female, Follow-Up Studies, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Cord Blood Stem Cell Transplantation, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Unrelated Donors
- Abstract
We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P<0.0001) and chronic graft-versus-host disease (26% vs. 52%; P=0.0005) were less frequent after unrelated cord blood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28%), and relapse or progression (28% vs. 35%) at 36 months. There were also no significant differences in 2-year progression-free survival (43% vs. 58%, respectively) and overall survival (36% vs. 51%) at 36 months. In a multivariate analysis, no differences were observed in the outcomes between the two stem cell sources except for a higher risk of neutrophil engraftment (hazard ratio=2.12; P<0.0001) and chronic graft-versus-host disease (hazard ratio 2.10; P=0.0002) after matched unrelated donor transplant. In conclusion, there was no difference in final outcomes after transplantation between umbilical cord blood and matched unrelated donor transplant. Umbilical cord blood is a valuable alternative for patients with lymphoid malignancies lacking an HLA-matched donor, being associated with lower risk of chronic graft-versus-host disease.
- Published
- 2014
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23. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial.
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Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Bertz H, Grishina O, and Socié G
- Subjects
- Acute Disease, Adolescent, Adult, Age Factors, Chronic Disease, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, HLA Antigens immunology, Hematopoietic Stem Cell Transplantation mortality, Histocompatibility Testing, Humans, Male, Middle Aged, Prospective Studies, Severity of Illness Index, Survival Rate, Transplantation, Homologous, Unrelated Donors, Antilymphocyte Serum therapeutic use, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Myeloablative Agonists therapeutic use, Transplantation Conditioning methods
- Abstract
Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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24. Radiation-free allogeneic conditioning with fludarabine, carmustine, and thiotepa for acute lymphoblastic leukemia and other hematologic malignancies necessitating enhanced central nervous system activity.
- Author
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Christopoulos P, Bertz H, Ihorst G, Marks R, Wäsch R, and Finke J
- Subjects
- Adult, Aged, Alemtuzumab, Antibodies, Monoclonal, Humanized therapeutic use, Carmustine therapeutic use, Central Nervous System physiopathology, Cyclosporine therapeutic use, Drug Administration Schedule, Female, Follow-Up Studies, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Recurrence, Survival Analysis, Thiotepa therapeutic use, Transplantation, Homologous, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Central Nervous System drug effects, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods
- Abstract
Total body irradiation has been the mainstay of conditioning since the inception of allogeneic hematopoietic cell transplantation, but toxicity often precludes its use. For less-fit patients with acute lymphoblastic leukemia and other hematologic malignancies frequently affecting the central nervous system, we designed a radiation-free regimen with fludarabine (25 mg/m2/day on days -6 to -4), carmustine (400 mg/m2 on day -6), and thiotepa (5 mg/kg twice daily on days -5 and -4), all of which readily penetrate the blood-brain barrier and have potent antileukemic and lymphotoxic activity. Here we present a series of 30 consecutive patients with high-risk or relapsed disease who underwent allogeneic hematopoietic cell transplantation with this protocol. The median patient age was 60 years (range, 42-70 years), and the median follow-up was 968 days (range, 58-1989 days). Graft-versus-host disease prophylaxis consisted of cyclosporine A and alemtuzumab (10-20 mg). At 2 years, overall survival was 52% (95% confidence interval [CI], 34%-71%), event-free survival was 39% (95% CI, 22%-57%), cumulative incidence of relapse/progression was 30% (95% CI, 17%-52%), and treatment-related mortality was 31% (95% CI, 18%-53%). Neurologic toxicity is a concern, especially in older and heavily pretreated patients. Our experience indicates the feasibility of this regimen as an alternative to total body irradiation and a potentially curative option for less-fit patients who need a highly central nervous system-active conditioning., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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25. Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine.
- Author
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Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G, Schaefer-Eckart K, Bornhäuser M, Itzykson R, Germing U, Beelen D, Ehninger G, Fenaux P, Deeg HJ, and Adès L
- Subjects
- Aged, Female, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes immunology, Myelodysplastic Syndromes mortality, Retrospective Studies, Risk, Survival Analysis, Tissue Donors, Transplantation, Homologous, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Transplantation Conditioning
- Abstract
Standard first-line therapy for older patients with high-risk myelodysplastic syndrome (MDS) includes hypomethylating agents, such as azacitidine (AZA). However, the only approach with curative potential remains allogeneic hematopoietic cell transplantation (HCT). To date, no direct comparison of both strategies has been reported. The outcomes of 2 well-balanced cohorts of patients with high-risk MDS defined by age (60-70 years), performance status (Eastern Cooperative Oncology Group score ≤2), and donor availability (yes/no) were compared, including 103 patients undergoing HCT and 75 patients without this option who received AZA. The estimated 2-year overall survival after the start of treatment was 39% (95% confidence interval, 30%-50%) for the patients undergoing HCT and 23% (95% confidence interval, 14%-40%) for the patients receiving AZA therapy. In a multivariate Cox regression analysis of all patients (n = 178), Eastern Cooperative Oncology Group score (0 versus 1 versus 2; hazard ratio [HR], 2.9/3.9; P < .001), cytogenetics (good versus intermediate versus poor; HR, 1.2/1.7; P = .026), and treatment (HCT versus AZA; HR, 0.3; P = .007) were associated with overall survival. This retrospective cohort analysis suggests a survival advantage for allogeneic HCT compared with AZA therapy in medically fit patients with high-risk MDS age 60-70 years. Prospective controlled studies are warranted., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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26. Marrow versus blood-derived stem cell grafts for allogeneic transplantation from unrelated donors in patients with active myeloid leukemia or myelodysplasia.
- Author
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Bertz H, Spyridonidis A, Ihorst G, Engelhardt M, Grüllich C, Wäsch R, Marks R, and Finke J
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- Adolescent, Adult, Antilymphocyte Serum administration & dosage, Antineoplastic Agents administration & dosage, Cyclosporine administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Germany, Humans, Leukemia, Myeloid, Acute immunology, Leukemia, Myeloid, Acute mortality, Male, Methotrexate administration & dosage, Middle Aged, Myelodysplastic Syndromes immunology, Myelodysplastic Syndromes mortality, Prospective Studies, Secondary Prevention, Severity of Illness Index, Transplantation, Homologous, Treatment Outcome, Unrelated Donors, Bone Marrow Transplantation, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes therapy, Peripheral Blood Stem Cell Transplantation, Transplantation Conditioning
- Abstract
Peripheral blood stem cells (PBSCs) are increasingly used as the graft source in allogeneic hematopoietic cell transplantation. We compared long-term outcome after unrelated donor transplantation of 85 consecutive patients with acute myelogenous leukemia or myelodysplastic syndrome regarding disease status (early disease [CR1, refractory anemia); n = 25 and advanced/active disease [>CR1, >refractory anemia]; n = 60) who were treated with conventional conditioning regimens followed by bone marrow (BM) or PBSC grafts. Graft-versus-host disease prophylaxis consisted mainly of cyclosporine A, short-course methotrexate, and anti-T-lymphocyte globulin. After a median follow-up of 118 months (68-174), the 10-year event-free survival rate after peripheral blood stem cell transplantation (PBSCT) was 54.8% (95% confidence interval [CI], 39.7%-69.8%), and after bone marrow transplantation (BMT), it was 27.9% (14.5%-41.3%; P < .004). In the advanced/active disease group, the 10-year event-free survival rate after PBSCT was 50% (30.8%-69.2%), and after BMT, it was 23.5% (9.3%-37.8%; P < .007). Non relapse mortality was less after PBSCT than BMT (14.3% vs 30.2%), respectively. In multivariate Cox regression analysis, PBSCT showed a better overall survival (OS; hazard ratio [HR], 0.43; 95% CI, 0.23-0.79; P = .007) compared to BMT; unfavorable/unknown prognostic impact cytogenetic abnormalities were an adverse factor for all patients (HR, 2.202; 95% CI, 1.19-4.06; P = .011). In patients with advanced disease, the use of PBSCs showed a significant favorable outcome via multivariate analysis (HR, 0.49; 95% CI, 0.24-0.99; P = .046). Outcome of acute myelogenous leukemia/myelodysplastic syndrome after unrelated hematopoietic cell transplantation is adversely affected by cytogenetic abnormalities and state of remission at hematopoietic cell transplantation. PBSC as a graft source has a significant favorable influence on survival., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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27. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies.
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Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, and Finke JM
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols toxicity, Carmustine administration & dosage, Female, Hematologic Neoplasms mortality, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Melphalan administration & dosage, Middle Aged, Survival Analysis, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods
- Abstract
Toxicity-reduced conditioning is being used for allogeneic stem cell transplantation in older and/or comorbid patients. We report on the treatment of 133 patients (median age: 55.6 years [23-73 years]) with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS; n = 81), myeloproliferative syndromes (MPS; n = 20), and lymphoid malignancies (n = 32) using conditioning with FBM: fludarabine (5 x 30 mg/m(2)), 1,3-bis(2-chloroethyl)-1-nitrosourea (or carmustine, BCNU; 2 x 200 mg/m(2)), and melphalan (140 mg/m(2)). Patients 55 years or older received fludarabine with reduced BCNU (2 x150 mg/m(2)) and melphalan (110 mg/m(2)). After engraftment, chimerism analyses revealed complete donor hematopoiesis in 95.7% of patients. With a median follow-up of 58.5 months, 3- and 5-year overall survival (OS) was 53.0% and 46.1%, event-free survival (EFS) was 46.4% and 41.9%. No significant differences in OS and EFS were evident considering disease status (early vs advanced), patient age (<55 vs> or =55 years), or donor type (related vs unrelated) in univariate and multivariate analyses. The cumulative 5-year incidence of death due to relapse was 20.1%. Nonrelapse mortality (NRM) after 100 days and 1 year was 15.8% and 26.3%. Among patients with AML/MDS, advanced cases (n = 64, including 61 with active disease) showed an OS of 44.6% and 42.4% after 3 and 5 years, respectively. Therefore, FBM conditioning combines effective disease control with low NRM.
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- 2008
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28. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes.
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Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J, Bacigalupo A, Beelen D, Reiffers J, Devergie A, Alessandrino E, Mufti GJ, Barge R, Sierra J, Ruutu T, Boogaerts M, Falda M, Jouet JP, Niederwieser D, and de Witte T
- Subjects
- Adolescent, Adult, Aged, Dose-Response Relationship, Drug, Female, HLA Antigens, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Myelodysplastic Syndromes mortality, Recurrence, Retrospective Studies, Siblings, Survival Analysis, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes therapy, Transplantation Conditioning methods
- Abstract
In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)-identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P = .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC group (HR, 0.61; 95% CI, 0.41-0.91; P = .015). The 3-year probabilities of progression-free and overall survivals were similar in both groups (39% after SMC vs 33% in RIC; multivariate P = .9; and 45% vs 41%, respectively; P = .8). In conclusion, the lower 3-year NRM after RIC is encouraging, since these patients were older (age > 50 years in 73% RIC vs 28% in SMC, P < .001) and had more adverse pretransplantation variables. However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS.
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- 2006
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29. Reduced intensity conditioning compared to standard conditioning preserves the in vitro growth capacity of bone marrow stroma, which remains of host origin.
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Spyridonidis A, Küttler T, Wäsch R, Samek E, Waterhouse M, Behringer D, Bertz H, and Finke J
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- Adult, Aged, Anemia, Aplastic therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Busulfan administration & dosage, Cell Proliferation, Cell Transplantation, Combined Modality Therapy, Cyclophosphamide administration & dosage, Etoposide administration & dosage, Female, Hematopoietic Stem Cells cytology, Humans, Immunohistochemistry, Immunosuppressive Agents administration & dosage, In Situ Hybridization, Fluorescence, Lewis X Antigen biosynthesis, Lipopolysaccharide Receptors biosynthesis, Lymphoma therapy, Male, Microscopy, Fluorescence, Middle Aged, Myelodysplastic Syndromes therapy, Nucleic Acid Synthesis Inhibitors administration & dosage, Stromal Cells cytology, Vidarabine administration & dosage, Vidarabine pharmacology, Bone Marrow Cells cytology, Bone Marrow Transplantation methods, Cell Culture Techniques methods, Transplantation Conditioning methods, Vidarabine analogs & derivatives
- Abstract
The ability of bone marrow (BM) samples to generate confluent stromal layers in long-term BM cultures (LTBMC) was used as a surrogate assay to determine the in vivo toxic effects of different conditionings on stromal cells. Here, 32 patients receiving a fludarabine-based reduced intensity conditioning regimen (FBM) were compared to those in a control group of 23 patients treated with standard busulfan/cyclophosphamide (BuCy; 14 patients) or TBI-based (TBI 12 Gy/VP16/cyclophosphamide; 9 patients) conditioning. BM was aspirated before conditioning, and at day +30 and/or at day +100, obtaining positive stromal cell growth in vitro in 58%, 47%, and 65%, respectively. FBM conditioning did not alter the ability of BM to generate stromal layers both early (day +30, 75%+) or late (day +100, 80%+) after hematopoietic cell transplantation (HCT) as compared to pre-HCT (66.6%+). FBM-treated patients formed confluent stroma significantly more often than standard-treated patients (85% vs. 38% patients; p < 0.05). In an univariate analysis, standard conditioning remained the only factor predicting stromal growth impairment after allogeneic HCT. The ex vivo-generated stromal layers from 5 female, FBM treated, sex-mismatched, and peripheral blood stem cell (PBSC) transplanted patients were analyzed by combined FISH-Y and immunofluorescence stains (Vimentin, CD14, CD45) and found to be exclusively of recipient origin. We conclude that FBM reduced intensity conditioning results in reduced, if any, stromal damage as compared to standard myeloablative treatment. The novel, donor-derived, hematopoiesis in FBM patients after allogeneic transplantation is supported and maintained by a host-derived BM stromal microenvironment.
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- 2005
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30. Treosulfan compared with <scp>reduced‐intensity</scp> busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial
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Beelen, Dietrich, Stelljes, Matthias, Reményi, Péter, Wagner‐Drouet, Eva‐Maria, Dreger, Peter, Bethge, Wolfgang, Ciceri, Fabio, Stölzel, Friedrich, Junghanß, Christian, Labussiere‐Wallet, Hélène, Schaefer‐Eckart, Kerstin, Grigoleit, Goetz U., Scheid, Christof, Patriarca, Francesca, Rambaldi, Alessandro, Niederwieser, Dietger, Hilgendorf, Inken, Russo, Domenico, Socié, Gérard, Holler, Ernst, Glass, Bertram, Casper, Jochen, Wulf, Gerald, Basara, Nadezda, Bieniaszewska, Maria, Stuhler, Gernot, Verbeek, Mareike, La Rocca, Ursula, Finke, Jürgen, Benedetti, Fabio, Pichlmeier, Uwe, Klein, Anja, Baumgart, Joachim, Markiewicz, Miroslaw, and Rocca, Ursula La
- Subjects
Leukemia, Myeloid, Acute ,Transplantation Conditioning ,Myelodysplastic Syndromes ,Medizin ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Prospective Studies ,Hematology ,Middle Aged ,Busulfan ,Vidarabine ,Aged - Abstract
The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer-term follow-up are presented. Patients presenting HCT-specific comorbidity index >2 or aged >= 50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m(2) IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36-months-EFS rate 59.5% (95% CI, 52.2-66.1) vs. 49.7% (95% CI, 43.3-55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49-0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36-month-OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48-0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.
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- 2022
31. Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
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Carré, Martin, Porcher, Raphaël, Finke, Jürgen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Friis, Lone, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Cascon, Maria Jesús Pascual, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Arat, Mutlu, de Witte, Theo, Yakoub Agha, Ibrahim, Kröger, Nicolaus, Robin, Marie, and Agha, Ibrahim Yakoub
- Subjects
Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Multivariate analysis ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Myelodysplastic syndromes ,Medizin ,Comorbidity ,Hematopoietic stem cell transplantation ,Comorbidities ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Age ,0302 clinical medicine ,Bone Marrow ,Neoplasms ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Nonrelapse mortality ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Settore MED/15 ,medicine.disease ,Settore MED/01 ,030220 oncology & carcinogenesis ,Stem cell ,business ,030215 immunology - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P.0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.
- Published
- 2020
32. Association of serum ferritin levels before start of conditioning with mortality after alloSCT: A prospective, non-interventional study of the EBMT transplant complications working party
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Penack, Olaf, Peczynski, Christophe, Werf, Steffie, van der, Finke, Jürgen, Ganser, Arnold, Schoemans, Helene, Pavlu, Jiri, Niittyvuopio, Riitta, Schroyens, Wilfried, Kaynar, Leylagül, Blau, Igor W., Velden, Walter J. F. M., van der, Sierra, Jorge, Cortelezzi, Agostino, Wulf, Gerald, Turlure, Pascal, Rovira, Montserrat, Ozkurt, Zubeydenur, Pascual-Cascon, Maria J., Moreira, Maria C., Clausen, Johannes, Greinix, Hildegard, Duarte, Rafael F., Basak, Grzegorz W., UAM. Departamento de Medicina, HUS Comprehensive Cancer Center, Hematologian yksikkö, Clinicum, and Department of Oncology
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Adult ,Male ,lcsh:Immunologic diseases. Allergy ,Transplantation Conditioning ,Adolescent ,IMPACT ,Medicina ,3122 Cancers ,Graft vs Host Disease ,ACUTE MYELOID-LEUKEMIA ,ALBUMIN ,DIAGNOSIS ,DISEASE RISK INDEX ,immunology ,Young Adult ,Postoperative Complications ,INFECTION ,Biomarkers, Tumor ,IRON OVERLOAD ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,iron metabolism ,Prospective Studies ,Original Research ,Aged ,Peripheral Blood Stem Cell Transplantation ,Science & Technology ,CELL TRANSPLANTATION ,ferritin ,Middle Aged ,stem cell ,Hematologic Neoplasms ,Ferritins ,1182 Biochemistry, cell and molecular biology ,biomarker ,Female ,3111 Biomedicine ,Human medicine ,lcsh:RC581-607 ,Life Sciences & Biomedicine ,transplantation - Abstract
Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5–4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6–3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2–3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5–6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6–9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT., JP acknowledges the support of the Imperial NIHR-BCR. OP acknowledges the support of José Carreras Leukämie-Stiftung (11R2016 and 3R2019), Deutsche Krebshilfe (70113519), and Deutsche Forschungsgemeinschaft (PE 1450/7-1)
- Published
- 2020
33. Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)
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Schetelig, Johannes, de Wreede, Liesbeth C., Andersen, Niels S., Moreno, Carol, van Gelder, Michel, Vitek, Antonin, Karas, Michal, Michallet, Mauricette, Machaczka, Maciej, Gramatzki, Martin, Beelen, Dietrich, Finke, Jürgen, Delgado, Julio, Volin, Liisa, Passweg, Jakob, Dreger, Peter, Schaap, Nicolaas, Wagner, Eva, Henseler, Anja, van Biezen, Anja, Bornhäuser, Martin, Iacobelli, Simona, Putter, Hein, Schönland, Stefan O., Kröger, Nicolaus, Esteve, Jordi, Ljungman, Per, de Witte, Theo, Stelljes, Matthias, Sierra, Jorge, Socié, Gerard, Ganser, Arnold, Wulf, Gerhard G., Deconinck, Eric, Faber, Edgar, Feguex, Nathalie, Gedde-Dahl, Tobias, Kolbe, Karin, Chalandon, Yves, Krüger, William, Huynh, Anne, Bourhis, Jean Henri, Schouten, Harry, Ribera Santasusana, Josep M., Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Chalandon, Yves
- Subjects
Oncology ,Male ,Transplantation Conditioning ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Chronic lymphocytic leukemia ,Medizin ,QUALITY MANAGEMENT-SYSTEM ,Kaplan-Meier Estimate ,risk factor analysis ,GUIDELINES ,Biochemistry ,allogeneic stem cell transplantation ,centre effects ,chronic lymphocytic leukaemia ,frailties ,Transplantation Conditioning / methods ,0302 clinical medicine ,Recurrence ,Risk Factors ,Leukemia, Lymphocytic, Chronic, B-Cell / mortality ,Registries ,Delivery of Health Care / statistics & numerical data ,IBRUTINIB ,ddc:616 ,0303 health sciences ,ALEMTUZUMAB ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Professional Practice ,Hematology ,Middle Aged ,3. Good health ,Europe ,030220 oncology & carcinogenesis ,ABT-199 ,Cohort ,SURVIVAL ,Alemtuzumab ,Female ,Europe / epidemiology ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Immunology ,Lower risk ,DIAGNOSIS ,Settore MED/01 - Statistica Medica ,03 medical and health sciences ,Leukemia, Lymphocytic, Chronic, B-Cell / therapy ,Hematopoietic Stem Cell Transplantation / methods ,Internal medicine ,medicine ,Humans ,Karnofsky Performance Status ,030304 developmental biology ,Aged ,Retrospective Studies ,business.industry ,Proportional hazards model ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Retrospective cohort study ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Confidence interval ,Surgery ,Professional Practice / statistics & numerical data ,Transplantation ,business ,Delivery of Health Care ,030215 immunology ,RESPONSES - Abstract
Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.
- Published
- 2017
34. Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial
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Finke, Jürgen, Schmoor, Claudia, Bethge, Wolfgang A., Ottinger, Hellmut, Stelljes, Matthias, Zander, Axel R., Volin, Liisa, Heim, Dominik A., Schwerdtfeger, Rainer, Kolbe, Karin, Mayer, Jiri, Maertens, Johan A., Linkesch, Werner, Holler, Ernst, Koza, Vladimir, Bornhäuser, Martin, Einsele, Hermann, Bertz, Hartmut, Grishina, Olga, Socié, Gérard, and for the ATG-Fresenius Trial Group
- Subjects
Male ,Oncology ,Transplantation Conditioning ,medicine.medical_treatment ,Medizin ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,HLA Antigens ,law ,immune system diseases ,hemic and lymphatic diseases ,Allogeneic hematopoietic stem-cell transplantation ,Medicine ,Prospective Studies ,Prospective cohort study ,Hematology ,Histocompatibility Testing ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,3. Good health ,Survival Rate ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Unrelated Donors ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Adolescent ,Graft-versus-host-disease prophylaxis ,03 medical and health sciences ,Internal medicine ,Humans ,Transplantation, Homologous ,HLA-matching ,Survival rate ,Antilymphocyte Serum ,Transplantation ,business.industry ,Myeloablative Agonists ,Chronic Disease ,Immunology ,business ,030215 immunology - Abstract
Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD. © 2012 American Society for Blood and Marrow Transplantation.
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35. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT
- Author
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Jordi Esteve, Gérard Socié, Fabio Ciceri, Jürgen Finke, Donald Bunjes, Myriam Labopin, Gerhard Ehninger, Norbert Claude Gorin, Bertram Glass, Nicolaus Kröger, Per Ljungman, Rainer Schwerdtfeger, Mohamad Mohty, Charles Craddock, Frédéric Baron, Sebastian Giebel, Bipin N. Savani, Arnon Nagler, Dietger Niederwieser, Christoph Schmid, Savani, Bipin N., Labopin, Myriam, Kröger, Nicolau, Finke, Jürgen, Ehninger, Gerhard, Niederwieser, Dietger, Schwerdtfeger, Rainer, Bunjes, Donald, Glass, Bertram, Socié, Gerard, Ljungman, Per, Craddock, Charle, Baron, Frédéric, Ciceri, Fabio, Gorin, Norbert Claude, Esteve, Jordi, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Acute leukemia ,business.industry ,Graft Survival ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Middle Aged ,Survival Analysis ,Surgery ,Transplantation ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,Female ,Unrelated Donors ,business ,030215 immunology - Abstract
The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being
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- 2016
36. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study
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Katie S. Gatwood, Jordi Esteve, Patrice Chevallier, Peter Dreger, Matthias Stelljes, Myriam Labopin, Bipin N. Savani, Norbert Claude Gorin, Arnold Ganser, Audrey Mailhol, Juergen Finke, Dietrich W. Beelen, Sebastian Giebel, Ghulam J. Mufti, Gerhard Ehninger, Arnon Nagler, Christoph Schmid, Frédéric Baron, Didier Blaise, Ariane Boumendil, Dietger Niederwieser, Mohamad Mohty, Fabio Ciceri, Salyka Sengsayadeth, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Hannover Medical School [Hannover] (MHH), Westfälische Wilhelms-Universität Münster (WWU), University of Münster, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Division Hematology, Oncology and Hemostasiology [Leipzig, Germany], University Hospital in Leipzig [Germany], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Medicine V, Universität Heidelberg [Heidelberg], King's College Hospital (KCH), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (DRPH/SRBE/LTCRA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Ludwig Maximilian University [Munich] (LMU), Cancer Center Gliwice, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gatwood, Katie S., Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N., Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (IRSN/DRPH/SRBE/LTCRA), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
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Adult ,Male ,medicine.medical_specialty ,Secondary ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Secondary Acute Myeloid Leukemia ,Cumulative incidence ,ddc:610 ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Acute leukemia ,Univariate analysis ,Transplantation ,Acute myeloid leukemia ,Toxicity ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Confidence interval ,3. Good health ,Allogeneic stem cell transplantation ,Europe ,Antileukemic effect ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology ,Conditioning - Abstract
International audience; Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [Cl], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% Cl, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (
- Published
- 2018
37. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study
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Sebastian Giebel, Arnold Ganser, Myriam Labopin, Audrey Mailhol, Peter Dreger, Gerhard Ehninger, Dietger Niederwieser, Ariane Boumendil, Dietrich W. Beelen, Norbert Claude Gorin, Salyka Sengsayadeth, Katie S. Gatwood, Fabio Ciceri, Jürgen Finke, Mohamad Mohty, Arnon Nagler, Matthias Stelljes, Patrice Chevallier, Ghulam J. Mufti, Frédéric Baron, Bipin N. Savani, Christoph Schmid, Didier Blaise, Maria H. Gilleece, Jordi Esteve, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sengsayadeth, Salyka, Gatwood, Katie S, Boumendil, Ariane, Labopin, Myriam, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gilleece, Maria H, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N, and Nagler, Arnon
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Cumulative incidence ,Registries ,Survival rate ,Aged ,Retrospective Studies ,Acute leukemia ,Univariate analysis ,Transplantation ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,food and beverages ,Retrospective cohort study ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Allografts ,3. Good health ,Survival Rate ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Myelodysplastic Syndromes ,Female ,business ,030215 immunology - Abstract
Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.
- Published
- 2018
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