32 results on '"Cornelissen, Jan"'
Search Results
2. Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial.
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van der Maas, Niek G., Versluis, Jurjen, Nasserinejad, Kazem, van Rosmalen, Joost, Pabst, Thomas, Maertens, Johan, Breems, Dimitri, Manz, Markus, Cloos, Jacqueline, Ossenkoppele, Gert J., Floisand, Yngvar, Gradowska, Patrycja, Löwenberg, Bob, Huls, Gerwin, Postmus, Douwe, Pignatti, Francesco, and Cornelissen, Jan J.
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ACUTE myeloid leukemia ,BAYESIAN analysis ,CLINICAL trials ,LONGITUDINAL method ,RANDOMIZED controlled trials - Abstract
Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a "7 + 3" induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81–1.69), 1.05 (95% CI 0.86–1.30), 1.00 (95% CI 0.84–1.19), and 1.02 (95% CI 0.87–1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR < 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Allogeneic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia: In vivo T-Cell Depletion and Posttransplant Sorafenib Maintenance Improve Survival. A Retrospective Acute Leukemia Working Party-European Society for Blood and Marrow Transplant Study
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Bazarbachi, Ali, Labopin, Myriam, Battipaglia, Giorgia, Djabali, Azedine, Forcade, Edouard, Arcese, William, Socié, Gerard, Blaise, Didier, Halter, Joerg, Gerull, Sabine, Cornelissen, Jan J., Chevallier, Patrice, Maertens, Johan, Schaap, Nicolaas, El-Cheikh, Jean, Esteve, Jordi, Nagler, Arnon, and Mohty, Mohamad
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- 2019
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4. The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed.
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Bakunina, Katerina, Putter, Hein, Versluis, Jurjen, Koster, Eva A. S., van der Holt, Bronno, Manz, Markus G., Breems, Dimitri A., Gjertsen, Bjorn T., Cloos, Jacqueline, Valk, Peter J. M., Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J., Löwenberg, Bob, Cornelissen, Jan J., and de Wreede, Liesbeth C.
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RANDOMIZED controlled trials ,HEMATOPOIETIC stem cell transplantation ,STEM cell transplantation ,ACUTE myeloid leukemia ,STEM cell treatment ,INDUCTION chemotherapy ,TREATMENT effectiveness - Abstract
Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi‐state models can provide additional insights to supplement the original intention‐to‐treat analysis of randomized controlled trials (RCT). We re‐analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi‐state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post‐remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post‐remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post‐remission treatment with alloSCT, non‐relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia‐free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi‐state models further detail the effect of treatment on competing and series of events. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Post‐transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA‐identical sibling donors: A retrospective analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Battipaglia, Giorgia, Labopin, Myriam, Hamladji, Rose‐Marie, Blaise, Didier, Chevallier, Patrice, Brissot, Eolia, Gerbitz, Armin, Socié, Gerard, Afanasyev, Boris, Ciceri, Fabio, Meijer, Ellen, Koc, Yener, Cornelissen, Jan J., Huynh, Anne, Ozdogu, Hakan, Maertens, Johan, Paul, Franciane, Labussière‐Wallet, Hélène, Ruggeri, Annalisa, and Aljurf, Mahmoud
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ACUTE myeloid leukemia ,STEM cell transplantation ,TOTAL body irradiation ,ACUTE leukemia ,CYCLOPHOSPHAMIDE ,HEMATOPOIETIC stem cell transplantation - Abstract
BACKGROUND: Graft‐versus‐host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents reduces GVHD in different donor settings. METHODS: We compared the outcomes of adults with acute myeloid leukemia undergoing allo‐HSCT from HLA‐identical sibling donors after the use of PTCY (n = 197) or ATG (n = 1913). RESULTS: Patients in the PTCY group were younger than those in the ATG group (median age, 47 vs 54 years; P <.01). Peripheral blood was the most frequently used stem cell source, being significantly more frequent in the ATG group than in the PTCY group (95% vs 70% P <.01). The conditioning regimen was more frequently myeloablative in the PTCY group than in the ATG group (59% vs 48%; P <.01). Time to neutrophil engraftment was shorter in the ATG group than in the PTCY group (17 vs 20 days; P <.01). No differences were observed according to the other transplantation outcomes, except for chronic GVHD of all grades and extensive chronic GVHD at 2 years, which were significantly lower in the ATG group compared with the PTCY group (P <.02). CONCLUSION: PTCY is feasible in an HLA‐identical sibling setting, and despite similar outcomes, ATG may be associated with lower incidence of chronic GVHD. Addition of antithymocyte globulin (ATG) or post‐transplantation cyclophosphamide (PTCY) to standard immunosuppressive agents in patients who received a transplant from an HLA‐identical sibling donor is feasible and allows low rates of graft‐versus‐host disease (GVHD).When compared with PTCY, the use of ATG is associated with lower cumulative incidence of chronic GVHD. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80%: A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT).
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Saraceni, Francesco, Labopin, Myriam, Forcade, Edouard, Kröger, Nicolaus, Socié, Gerard, Niittyvuopio, Riitta, Cornelissen, Jan J., Labussière‐Wallet, Hélène, Blaise, Didier, Choi, Goda, Byrne, Jenny L., Guillerm, Gaelle, Marchand, Tony, Esteve, Jordi, Bazarbachi, Ali, Savani, Bipin, Olivieri, Attilio, Nagler, Arnon, and Mohty, Mohamad
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KARNOFSKY Performance Status ,ACUTE myeloid leukemia ,STEM cell transplantation ,ACUTE leukemia ,BONE marrow - Abstract
Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo‐SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo‐SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two‐year leukemia‐free survival (LFS), overall survival (OS) and graft‐versus‐host disease (GVHD)‐free, and relapse‐free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non‐relapse mortality (NRM) and superior OS in comparison to patients with a KPS score <80% (p < 0.001). In the subgroup of patients with a KPS score =80%, a reduced‐intensity conditioning (RIC) regimen was associated with an increased risk of relapse (p = 0.002) and lower GRFS (p < 0.001) compared to myeloablative conditioning (MAC). Differently, in patients with a KPS score <80%, a RIC regimen resulted in lower NRM (p < 0.001), whereas relapse incidence did not differ, thus leading to an improved GRFS (p = 0.008) as compared to MAC. A transplant from a matched sibling donor (MSD) was associated with a reduced incidence of grade III‐IV acute GVHD (p < 0.01) and NRM (p < 0.01) in comparison to other donor types. In conclusion, allo‐SCT appears feasible in AML patients with a jeopardized KPS score. Survival is significantly affected by the conditioning intensity, which should be adjusted according to the severity of KPS impairment. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT.
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Sanz, Jaime, Galimard, Jacques-Emmanuel, Labopin, Myriam, Afanasyev, Boris, Angelucci, Emanuele, Ciceri, Fabio, Blaise, Didier, Cornelissen, Jan J., Meijer, Ellen, Diez-Martin, J. L., Koc, Yener, Rovira, Montserrat, Castagna, Luca, Savani, Bipin, Ruggeri, Annalisa, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,TRANSPLANTATION of organs, tissues, etc. ,STEM cell transplantation ,GRAFT versus host disease ,SIBLINGS - Abstract
Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia.
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Schmaelter, Ann-Kristin, Labopin, Myriam, Socié, Gerard, Itälä-Remes, Maija, Blaise, Didier, Yakoub-Agha, Ibrahim, Forcade, Edouard, Cornelissen, Jan, Ganser, Arnold, Beelen, Dietrich, Labussière-Wallet, Hélène, Passweg, Jakob, Savani, Bipin N., Schmid, Christoph, Nagler, Arnon, and Mohty, Mohamad
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CANCER chemotherapy ,BLOOD diseases ,ACUTE myeloid leukemia ,GRAFT versus host disease ,STEM cell transplantation - Abstract
Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p < 10
−5 ), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p < 10−5 ) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p < 10−4 ) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p < 10−4 ) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p < 10−3 ). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1. [ABSTRACT FROM AUTHOR]- Published
- 2020
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9. Impact of Postremission Consolidation Chemotherapy on Outcome After Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation for Patients With Acute Myeloid Leukemia in First Complete Remission
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Yeshurun, M, Labopin, M, Blaise, D, Cornelissen, Jan, Sengeloev, H, Vindelov, L, Kuball, J, Chevallier, P, Craddock, C, Socie, G, Bilger, K, Schouten, HC (Harry), Fegueux, N, Goker, H, Maertens, J, Bunjes, D, Arnold, R, Nagler, A, Mohty, M, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Hematology, and Cardiology
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SDG 3 - Good Health and Well-being ,complete remission ,allogeneic stem cell transplantation (alloSCT) ,acute myeloid leukemia ,consolidation ,reduced-intensity conditioning - Abstract
BACKGROUNDThe objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). METHODSOf the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen-matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received 1 consolidation chemotherapy cycle. RESULTSWith a median follow-up of 36 months (range, 2 months-135 months), the 3-year cumulative recurrence incidence (RI) was not significantly different between the groups (36%4% for the group treated without consolidation chemotherapy vs 38%3% for patients who received consolidation chemotherapy; P=.89). In addition, leukemia-free survival was similar between the groups (45%+/- 4% and 47%+/- 3%, respectively; P=.41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation (1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84-1.97 [P=.24]) or leukemia-free survival (hazards ratio, 1.00; 95% confidence interval, 0.71-1.42 [P=.99]). CONCLUSIONSThe data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available. Cancer 2014;120:855-863. (c) 2013 American Cancer Society. There is no apparent advantage for postremission consolidation chemotherapy before reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete response. Provided a suitable donor is readily available, transplantation should be offered promptly at the time the first complete response is achieved, without undue delay.
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- 2014
10. Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center.
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Ciurea, Stefan O., Labopin, Myriam, Socie, Gerard, Volin, Liisa, Passweg, Jakob, Chevallier, Patrice, Beelen, Dietrich, Milpied, Noel, Blaise, Didier, Cornelissen, Jan J., Fegueux, Nathalie, Polge, Emmanuelle, Kongtim, Piyanuch, Rondon, Gabriela, Esteve, Jordi, Mohty, Mohamad, Savani, Bipin N., Champlin, Richard E., and Nagler, Arnon
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ACUTE myeloid leukemia treatment ,KARYOTYPES ,CANCER relapse ,CANCER patients ,HEMATOPOIETIC stem cell transplantation - Abstract
Background: Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post-transplantation survival in a large cohort of patients with CK AML.Methods: In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis. The median patient age was 52 years. The donors were human leukocyte antigen-matched related donors (N = 749), matched unrelated donors (N = 513), and mismatched unrelated donors (N = 80).Results: Relapse was the main cause of treatment failure. Overall, 51% of patients relapsed, 17.6% died of treatment-related mortality, and 31.3% survived leukemia-free. In multivariate analysis, the factors associated with an increased risk of relapse were age (>40 years; hazard ratio [HR], 1.1 per 10 years; P = .02), secondary AML (HR, 1.35; P = .01), active disease at transplantation (HR, 1.98; P < .001), and deletion/monosomy 5 (HR, 1.5; P < .001); whereas age (HR, 1.15 per 10 years; P < .001), secondary AML (HR, 1.36; P = .001), active disease at transplantation (HR, 1.99; P < .001), deletion/monosomy 5 (HR, 1.24; P = .008), and deletion/monosomy 7 (HR, 1.44; P < .001) predicted for leukemia-free survival.Conclusions: Disease relapse remains the most common cause of treatment failure for patients with CK AML after transplantation. Novel approaches to decrease the relapse rate and improve survival are needed in these patients. Cancer 2018;124:2134-41. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2018
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11. Etanercept for steroid-refractory acute graft-versus-host disease: A single center experience.
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De Jong, Cornelis N., Saes, Lotte, Klerk, Clara P. W., Van der Klift, Marjolein, Cornelissen, Jan J., and Broers, Annoek E. C.
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GRAFT versus host disease ,STEM cell transplantation ,STEROIDS ,CYCLOSPORINE ,MYCOPHENOLIC acid - Abstract
Background: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. Methods: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. Results: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5–267) for the entire group. Median overall survival was 99 days (range 47–267 days) for responders and 17 days (range 5–66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). Conclusion: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients. [ABSTRACT FROM AUTHOR]
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- 2017
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12. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
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Gorin, Norbert‐Claude, Labopin, Myriam, Czerw, Tomasz, Pabst, Thomas, Blaise, Didier, Dumas, Pierre‐Yves, Nemet, Damir, Arcese, William, Trisolini, Silvia Maria, Wu, Depei, Huynh, Anne, Zuckerman, Tsila, Meijer, Ellen, Cagirgan, Seckin, Cornelissen, Jan, Houhou, Mohamed, Polge, Emmanuelle, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,BUSULFAN ,MELPHALAN ,CYCLOPHOSPHAMIDE ,RETROSPECTIVE studies - Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation. METHODS From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%. RESULTS Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P = .003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P = .005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P = .03). CONCLUSIONS In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]
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- 2017
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13. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
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Poiré, Xavier, Labopin, Myriam, Maertens, Johan, Yakoub-Agha, Ibrahim, Blaise, Didier, Ifrah, Norbert, Socié, Gérard, Gedde-Dhal, Tobias, Schaap, Nicolaas, Cornelissen, Jan J., Vigouroux, Stéphane, Sanz, Jaime, Michaux, Lucienne, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,DISEASE remission ,PROGNOSIS ,TREATMENT effectiveness ,THERAPEUTICS - Abstract
Background: Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. Methods: To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results: One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions: In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1. [ABSTRACT FROM AUTHOR]
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- 2017
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14. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT.
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Saraceni, Francesco, Labopin, Myriam, Gorin, Norbert-Claude, Blaise, Didier, Tabrizi, Reza, Volin, Liisa, Cornelissen, Jan, Cahn, Jean-Yves, Chevallier, Patrice, Craddock, Charles, Depei Wu, Huynh, Anne, Arcese, William, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE myeloid leukemia ,DISEASE remission ,GRAFT versus host disease ,HEMATOLOGIC malignancies ,CANCER ,LYMPHOMAS - Abstract
Background: Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting auto-HSCT with allo-HSCT from unrelated donor (UD-HSCT), especially mismatched UD-HSCT. Methods: We retrospectively compared outcome of allogeneic transplantation from matched (10/10 UD-HSCT) or mismatched at a single HLA-locus unrelated donor (9/10 UD-HSCT) to autologous transplantation in patients with AML in first complete remission (CR1). A total of 2879 patients were included; 1202 patients received auto-HSCT, 1302 10/10 UD-HSCT, and 375 9/10 UD-HSCT. A propensity score-weighted analysis was conducted to control for disease risk imbalances between the groups. Results: Matched 10/10 UD-HSCT was associated with the best leukemia-free survival (10/10 UD-HSCT vs auto-HSCT: HR 0.7, p = 0.0016). Leukemia-free survival was not statistically different between auto-HSCT and 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 0.8, p = 0.2). Overall survival was similar across the groups (10/10 UD-HSCT vs auto-HSCT: HR 0.98, p = 0.84; 9/10 UD-HSCT vs auto-HSCT: HR 1.1, p = 0.49). Notably, in intermediate-risk patients, OS was significantly worse for 9/10 UD-HSCT (9/10 UD-HSCT vs auto-HSCT: HR 1.6, p = 0.049), while it did not differ between auto-HSCT and 10/10 UD-HSCT (HR 0.95, p = 0.88). In favorable risk patients, auto-HSCT resulted in 3-year LFS and OS rates of 59 and 78 %, respectively. Conclusions: Our findings suggest that in AML patients in CR1 lacking an HLA-matched sibling donor, 10/10 UD-HSCT significantly improves LFS, but this advantage does not translate in better OS compared to auto-HSCT. In intermediate-risk patients lacking a fully HLA-matched donor, auto-HSCT should be considered as a valid option, as better survival appears to be provided by auto-HSCT compared to mismatched UD-HSCT. Finally, auto-HSCT provided an encouraging outcome in patients with favorable risk AML. [ABSTRACT FROM AUTHOR]
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- 2016
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15. Long-term follow-up of patients with acute myeloid leukemia surviving and free of disease recurrence for at least 2 years after autologous stem cell transplantation: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Czerw, Tomasz, Labopin, Myriam, Gorin, Norbert‐Claude, Giebel, Sebastian, Blaise, Didier, Meloni, Giovanna, Pigneux, Arnaud, Bosi, Alberto, Veelken, Joan, Ferrara, Felicetto, Schaap, Nicolaas, Lemoli, Roberto M., Cornelissen, Jan J., Beohou, Eric, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia ,CANCER patients ,CANCER relapse ,AUTOTRANSPLANTATION ,STEM cell transplantation ,MORTALITY - Abstract
Background: Leukemia recurrence is a major cause of treatment failure after autologous stem cell transplantation for acute myeloid leukemia (AML). It usually occurs within the first 2 years after transplantation. The goal of the current retrospective study was to assess the follow-up of and characterize risk factors for outcome among patients who survived free of disease recurrence after this period.Methods: The analysis included 3567 adults (median age, 45 years) with AML who underwent autografting during the first (86% of patients) or second (14% of patients) complete remission between 1990 and 2008. The stem cell source was the bone marrow in 32% of patients or the peripheral blood in 68% of patients. The median follow-up was 6.9 years.Results: At 5 years and 10 years after transplantation, the probability of leukemia-free survival was 86% and 76%, respectively; the recurrence incidence was 11% and 16%, respectively; and the nonrecurrence mortality rate was 3% and 8%, respectively. The observed survival was decreased compared with the expected survival of the general European population. In a multivariate analysis, decreased probability of leukemia-free survival was demonstrated for patients who underwent peripheral blood autologous stem cell transplantation; had French-American-British subtypes M0, M6, or M7; and were of an older age. The same factors were found to be associated with an increased risk of disease recurrence. Nonrecurrence mortality was found to be affected by older age.Conclusions: The results of the current analysis indicate that late recurrences remain a major concern after autologous stem cell transplantation among patients with AML, indicating the need for close monitoring of minimal residual disease and additional leukemic control measures after transplantation. Cancer 2016;122:1880-7. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2016
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16. Hematopoietic stem cell transplantation for patients with AML in first complete remission.
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Cornelissen, Jan J. and Blaise, Didier
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HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia , *DISEASE relapse , *PROTEIN-tyrosine kinases , *GRAFT versus host disease - Abstract
Postremission therapy in patients with acute myeloid leukemia (AML) may consist of continuing chemotherapy or transplantation using either autologousor allogeneic stem cells. Patients with favorable subtypes of AML generally receive chemotherapeutic consolidation, although recent studies have also suggested favorable outcome after hematopoietic stem cell transplantation (HSCT). Although allogeneic HSCT (alloHSCT) is considered the preferred type of postremission therapy in poor- and very-poor-risk AML, the place of alloHSCT in intermediate-risk AML is being debated, and autologous HSCT is considered a valuable alternative that may be preferred in patients withoutminimal residual disease after induction chemotherapy. Here, we review postremission transplantation strategies using either autologous or allogeneic stem cells. Recent developments in the field of alternative donors, including cord blood and haploidentical donors, are highlighted, and we discuss reduced-intensity alloHSCT in older AML recipients who represent the predominant category of patients with AML who have a high risk of relapse in first remission. [ABSTRACT FROM AUTHOR]
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- 2016
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17. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
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Eder, Sandra, Labopin, Myriam, Arcese, William, Or, Reuven, Majolino, Ignazio, Bacigalupo, Andrea, Rosa, Gennaro, Volin, Liisa, Beelen, Dietrich, Veelken, Hendrik, Schaap, Nicolaas P. M., Kuball, Jurgen, Cornelissen, Jan, Nagler, Arnon, and Mohty, Mohamad
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THIOTEPA ,ORGANOTHIOPHOSPHORUS compounds ,TOTAL body irradiation ,GRAFT versus host disease ,STEM cell transplantation ,ACUTE myeloid leukemia ,PATIENTS - Abstract
Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the longestablished ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. [ABSTRACT FROM AUTHOR]
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- 2016
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18. Mobilized peripheral blood stem cells compared with bone marrow from HLA-identical siblings for reduced-intensity conditioning transplantation in acute myeloid leukemia in complete remission: a retrospective analysis from the Acute Leukemia Working Party of EBMT
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Nagler, Arnon, Labopin, Myriam, Shimoni, Avichai, Mufti, Ghulam J., Cornelissen, Jan J., Blaise, Didier, Janssen, Jeroen J. W. M., Milpied, Noel, Vindelov, Lars, Petersen, Eefke, Gribben, John, Bacigalupo, Andrea, Malm, Claes, Niederwieser, Dietger, Socié, Gerard J., Arnold, Renate, Brown, Paul, Goker, Hakan, Rocha, Vanderson, and Mohty, Mohamad
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ACUTE myeloid leukemia ,STEM cell transplantation ,BONE marrow ,HISTOCOMPATIBILITY antigens ,ACUTE leukemia - Abstract
Reduced-intensity conditioning ( RIC)-allo SCT is increasingly used for acute myelogenous leukemia. Limited data are available for the comparison of peripheral blood stem cells with bone marrow for RIC-allo SCT. We used the European Group for Blood and Marrow Transplantation ( EBMT) ALWP data to compare the outcome of mobilized peripheral blood stem cells ( PBSC) ( n = 1430) vs. bone marrow ( BM) ( n = 107) for acute myelogenous leukemia ( AML) patients with complete remission that underwent RIC-allo SCT from compatible sibling donors. The leukemia features, the disease status, and the time from diagnosis were similar between the two groups. Engraftment was achieved in 99% and 93% in the PBSC and BM groups, respectively ( P < 0.0001). The day of engraftment was significantly earlier for the PBSC vs. the BM group, 15 (1-59) and 19 (5-69), respectively ( P < 0.001). Acute GVHD, severe GVHD (grade III-IV) and chronic GVHD did not differ between the groups. leukemia-free survival ( LFS), relapse, and non-relapsed mortality ( NRM) were 51 ± 2%, 32 ± 1%, and 17 ± 1% vs. 50 ± 6%, 38 ± 6%, and 12 ± 3% for the PBSC and BM groups, respectively. Our results indicate faster engraftment, but no difference in GVHD, LFS, relapse, and NRM when comparing PBSC to BM grafts from sibling donors following RIC conditioning. This is the first study comparing PBSC to BM grafts in the RIC setting, analyzing a homogeneous population of patients with AML in remission. Whether PBSC should be preferred for advanced phases of the disease, where the outcome is dominated by relapse incidences, needs further investigation. [ABSTRACT FROM AUTHOR]
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- 2012
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19. Allogeneic stem cell transplantation in acute myeloid leukemia: a risk-adapted approach.
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Lodewyck, Tom and Cornelissen, Jan J.
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STEM cell transplantation ,ACUTE myeloid leukemia ,HEMATOPOIETIC stem cells ,DRUG therapy ,RADIOTHERAPY ,IMMUNOTHERAPY ,PATIENTS - Abstract
Summary: Allogeneic hematopoietic stem cell transplantation (alloSCT) is nowadays most frequently applied in patients with acute myeloid leukemia (AML). It combines chemoradiotherapy with immunotherapy, also known as the graft-versus-leukemia (GVL) effect. While it effectively reduces the relapse rate in patients, transplanted in remission, non-relapse mortality (NRM) may counterbalance that beneficial effect. As a result, alloSCT is generally associated with a modest gain in overall survival. Therefore, alloSCT may especially be applied in patients with a relatively high risk of relapse and a relatively low risk of NRM. Here, we discuss how recent findings that have identified and validated specific prognostic factors may affect our decision making for which category of AML-patients alloSCT may especially be indicated. [Copyright &y& Elsevier]
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- 2008
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20. Autologous stem cell transplantation for adult acute myelocytic leukemia in first remission-Better outcomes after busulfan and melphalan compared with busulfan and cyclophosphamide: A retrospective study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
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Gorin, Norbert-Claude, Labopin, Myriam, Czerw, Tomasz, Pabst, Thomas, Blaise, Didier, Dumas, Pierre-Yves, Nemet, Damir, Arcese, William, Trisolini, Silvia Maria, Wu, Depei, Huynh, Anne, Zuckerman, Tsila, Meijer, Ellen, Cagirgan, Seckin, Cornelissen, Jan, Houhou, Mohamed, Polge, Emmanuelle, Mohty, Mohamad, and Nagler, Arnon
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ANTINEOPLASTIC agents ,STEM cell transplantation ,CYCLOPHOSPHAMIDE ,MELPHALAN ,BUSULFAN ,AUTOGRAFTS ,COMBINED modality therapy ,IMMUNOSUPPRESSION ,ACUTE myeloid leukemia ,DISEASE remission ,RETROSPECTIVE studies ,THERAPEUTICS - Abstract
Background: Autologous stem cell transplantation (ASCT) for adult acute myelogenous leukemia (AML) is a valid therapeutic option for patients with good-risk and intermediate-risk disease. The authors used the registry of the European Society for Blood and Marrow Transplantation to compare combined busulfan and melphalan (BUMEL) with combined busulfan and cyclophosphamide (BUCY) before transplantation.Methods: From 2005 to 2013, 853 patients with available cytogenetics underwent ASCT in first remission, including 257 after receiving BUMEL and 596 after receiving BUCY. The proportion of patients with good-risk AML was lower in those who received BUMEL (14% vs 20%; P = .02). More patients who received BUMEL underwent autograft in molecular remission (89% vs 78%; P = .02). Three years after transplantation, the relapse incidence (RI) was 48.7%, the leukemia-free survival (LFS) rate was 47.7%, the overall survival (OS) rate was 66.2%, and the nonrelapse mortality (NRM) rate was 3.6%.Results: Patients who underwent an autograft after receiving BUMEL fared better than those who underwent an autograft after receiving BUCY with a lower RI (39.5% vs 52.2%; hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49-0.87; P = .003) a better LFS (55.4% vs 44.6%; HR, 0.69; 95% CI, 0.53-0.89; P = .005), and a better OS (73.8% vs 63%; HR, 0.62; 95% CI, 0.47-0.82; P = .0007). There was no difference in the NRM rate (BUMEL vs BUCY, 4.5% vs 3.2%, respectively). Among 74 patients in the BUMEL group and 187 in the BUCY group who underwent autograft in molecular remission, the RI was 30% versus 51%, respectively (univariate analysis; P = .01), and the LFS rate was 66% versus 47%, respectively (univariate analysis; P = .03).Conclusions: In patients with AML in first complete remission who undergo ASCT, the BUMEL combination is a better preparative regimen. Cancer 2017;123:824-31. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2016
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21. Old wine in a new bottle: ready to drink?
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Cornelissen, Jan J.
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DISEASE relapse , *ACUTE myeloid leukemia , *HEMATOPOIETIC stem cells , *CYTARABINE , *ANTHRACYCLINES , *PATIENTS - Abstract
The article presents a study on the impact of minimal residual disease (MRD) on progression-free survival, relapse, and overall survival of patients in acute myeloid leukemia (AML) patients who undergo an allogenic hematopoietic stem cell transplantation. It states that higher relapse rate in MRD-positive patients does not mean that graft-vs-leukemia (GVL) is absent. It is suggested that the effect of cytarabine and anthracycline in AML needs to be assessed to achieve optimal information.
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- 2013
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22. Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.
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Middeke, Jan M., Min Fang, Cornelissen, Jan J., Mohr, Brigitte, Appelbaum, Frederick R., Stadler, Michael, Sanz, Jaime, Baurmann, Herrad, Bug, Gesine, Schäfer-Eckart, Kerstin, Hegenbart, Ute, Bochtler, Tilmann, Röllig, Christoph, Stölzel, Friedrich, Walter, Roland B., Ehninger, Gerhard, Bornhäuser, Martin, Löwenberg, Bob, and Schetelig, Johannes
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ACUTE myeloid leukemia , *CHROMOSOME abnormalities , *CANCER chemotherapy , *HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *CONFIDENCE intervals - Abstract
Patients with acute myeloid leukemia (AML) and abnormalities of chromosome 17p (abnl(17p)) are at high-risk of treatment failure. Poor outcomes have been reported with conventional chemotherapy. To accurately define the outcome after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with abnl(17p) AML, we analyzed the results of patients with this abnormality who received an allogeneic HSCT between January 2000 and December 2010 in 1 of 4 well-defined cohorts (Fred Hutchinson Cancer Research Center, Haemato Oncology Foundation for Adults in the Netherlands, Study Alliance Leukemia, German Cooperative Transplant Study Group). Data of 201 patients with a median age of 54 years were evaluable. At the time of analysis, 30 patients were alive with a median follow-up of 30 months. The 3-year probability of overall survival (OS) was 15% (95% confidence interval [CI], 10-20). The cumulative incidence of relapse at 3 years was 49% (95% CI, 42-56). Notably, almost 70% of all relapses occurred within the first 6 months after HSCT. Patients who were transplanted in first complete remission (CR1) had superior OS compared with those with advanced disease (22% vs 9%, P < .001). Our findings confirm the high-risk of treatment failure in abnl(17p) AML even after allogeneic HSCT in CR1. Although allogeneic HSCT remains a valid option in CR1, alternative treatment strategies are needed for the remaining patients. [ABSTRACT FROM AUTHOR]
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- 2014
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23. Reduced-Intensity versus Myeloablative Conditioning in Cord Blood Transplantation for Acute Myeloid Leukemia (40-60 years) across Highly Mismatched HLA Barriers—On Behalf of Eurocord and the Cellular Therapy & Immunobiology Working Party (CTIWP) of EBMT
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Sheth, Vipul, Volt, Fernanda, Sanz, Jaime, Clement, Laurence, Cornelissen, Jan, Blaise, Didier, Sierra, Jorge, Michallet, Mauricette, Saccardi, Riccardo, Rocha, Vanderson, Gluckman, Eliane, Chabannon, Christian, and Ruggeri, Annalisa
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CORD blood transplantation , *ACUTE myeloid leukemia , *CELLULAR therapy , *CORD blood , *ALEMTUZUMAB , *IMMUNOLOGY , *GRAFT versus host disease - Abstract
• In HLA mismatched umbilical cord blood transplantation (UCBT), reduced-intensity conditioning provided comparable results to myeloablative conditioning for patients with acute myeloid leukemia (AML) aged 40 to 60 years. • The main factor associated with poor outcomes after HLA mismatched UCBT was advanced disease status. • UCBT remains an alternative graft source for patients 40 to 60 years old with AML. The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P =.9), NRM (HR, 0.68; P =.2), and relapse (HR, 1.24; P =.5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen. [ABSTRACT FROM AUTHOR]
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- 2020
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24. 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, Avichai, Labopin, Myriam, Savani, Bipin, Byrne, Michael, Volin, Liisa, Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, Jan J., Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *SIBLINGS , *BONE marrow , *ALEMTUZUMAB - Abstract
• Marked improvement has been achieved in recent years in stem cell transplantation (SCT) from unrelated donors. • Long-term outcome is equivalent after SCT from unrelated and sibling donors. • Patients who are leukemia-free 2 years after SCT can expect a favorable outcome. 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. [ABSTRACT FROM AUTHOR]
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- 2019
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25. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.
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Schmid, Christoph, Labopin, Myriam, Socié, Gerard, Daguindau, Etienne, Volin, Liisa, Huynh, Anne, Bourhis, Jean Henri, Milpied, Noel, Cornelissen, Jan, Chevallier, Patrice, Maertens, Johan, Jindra, Pavel, Blaise, Didier, Lenhoff, Stig, Ifrah, Norbert, Baron, Frédéric, Ciceri, Fabio, Gorin, Claude, Savani, Bipin, and Giebel, Sebastian
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STEM cell transplantation , *ACUTE myeloid leukemia , *GRAFT versus host disease , *CANCER chemotherapy , *GENETIC mutation - Abstract
To analyze the influence of distinct combinations ofmolecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1mut) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein a gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS fromHSCTwas 81 ± 5% in NPM1mut/FLT3wt, 75 ± 3% in NPM1wt/FLT3wt, 66 ± 3% in NPM1mut/ FLT3-ITD, and 54 ± 7% in NPM1wt/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1wt/FLT3wt revealed excellent results both in patients with CEBPαmut and with atriple negative genotype(2-year OS:100%/77 ± 3%). In aCox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). [ABSTRACT FROM AUTHOR]
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- 2015
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26. Aerosolised liposomal amphotericin B to prevent aspergillosis in acute myeloid leukaemia: Efficacy and cost effectiveness in real-life.
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Chong, Ga-Lai M., Broekman, Fleur, Polinder, Suzanne, Doorduijn, Jeanette K., Lugtenburg, Pieternella J., Verbon, Annelies, Cornelissen, Jan J., and Rijnders, Bart J.A.
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AMPHOTERICIN B , *AEROSOL therapy , *ASPERGILLOSIS , *ACUTE myeloid leukemia , *DRUG efficacy , *NEUTROPENIA , *CHEMOTHERAPY complications , *PREVENTION , *THERAPEUTICS - Abstract
Chemotherapy-induced neutropenia can be complicated by invasive pulmonary aspergillosis (IPA). In 2008, liposomal amphotericin B (L-AmB) inhalation was shown to prevent IPA in a placebo-controlled trial. Patients with acute myeloid leukaemia (AML) are the subset of haematology patients at high risk for IPA. In 2008, L-AmB inhalation prophylaxis became the standard of care for all AML patients in Erasmus MC. In this study, the efficacy and cost effectiveness of L-AmB inhalation were evaluated in a prospective cohort of AML patients. In total, 127 consecutive AML patients received chemotherapy and prophylactically inhaled L-AmB during their first and second chemotherapy cycles; 108 patients treated for AML at the same sites from 2005–2008 served as controls. A standardised diagnostic protocol was used and probable/proven IPA served as the primary endpoint. Diagnostic and therapeutic costs were also comprehensively analysed and compared. A significant decrease in probable/proven IPA in the L-AmB inhalation group was observed (L-AmB 9.5% vs. controls 23.4%; P = 0.0064). Systemic antifungal therapy given at any time during the entire AML therapy decreased from 52.8% to 29.9%. Per-patient equipment and drug costs for L-AmB inhalation (1292 €/patient) were more than compensated for by a decrease in costs for diagnostics and therapeutic voriconazole use (−1816 €/patient). No serious adverse events related to L-AmB inhalation were observed. In an unselected AML patient group, L-AmB inhalation resulted in a significant and substantial decrease in IPA and was cost saving. Now that azole resistance is more frequent, non-azole-based prophylaxis may become an attractive strategy. [ABSTRACT FROM AUTHOR]
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- 2015
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27. Mobilized Peripheral Blood Stem Cells Compared with Bone Marrow as the Stem Cell Source for Unrelated Donor Allogeneic Transplantation with Reduced-Intensity Conditioning in Patients with Acute Myeloid Leukemia in Complete Remission: An Analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation
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Nagler, Arnon, Labopin, Myriam, Shimoni, Avichai, Niederwieser, Dietger, Mufti, Ghulam J., Zander, Axel R., Arnold, Renate, Greinix, Hildegard, Cornelissen, Jan J., Jackson, Graham H., Craddock, Charles, Bunjes, Donald W., Ganser, Arnold, Russell, Nigel H., Kyrcz-Krzemien, Slawomira, Rocha, Vanderson, and Mohty, Mohamad
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BLOOD cells , *BONE marrow , *HEMATOPOIETIC stem cell transplantation , *BLOOD donors , *HOMOGRAFTS , *ACUTE myeloid leukemia , *RETROSPECTIVE studies - Abstract
Reduced-intensity conditioning allogeneic stem cell transplant (RIC-alloSCT) is being increasingly used for patients with acute myelogenous leukemia (AML) with comorbidities. Few published data are currently available regarding for the use of peripheral blood stem cells (PBSCs) compared to bone marrow (BM) in the RIC-alloSCT using unrelated donors (URDs). This retrospective report compared the outcomes of PBSC versus BM RIC-alloSCT. Between 2000 and 2007, 602 patients with AML in complete remission (CR) underwent RIC-alloSCT from URDs with PBSC (508) or BM (94) grafts. Recipient''s age was higher in the PBSC versus BM groups 57 (range, 17-77 years) and 51 (range, 17-76 years), respectively (P < .0001). Leukemia features and disease status at RIC-alloSCT were also comparable between the PBSC versus BM groups. Engraftment was achieved in 97% and 96% with BM versus peripheral blood (PB), respectively. Acute graft-versus-host disease (aGVHD) grade >II was significantly higher in the PBSC group: 27% versus 12% in the BM group (P < .002). Similarly, chronic graft-versus-host disease (cGVHD; at 2 years) was somewhat higher in the PBSC group with 43% ± 3% versus 35% ± 6% in the BM group, respectively (P = .04). The 2-year probabilities of leukemia-free survival (LFS) were 46% ± 3% for the PBSC group in comparison to 43% ± 6% for the BM transplant group (P = NS), whereas relapse incidence was significantly higher in the BM versus the PB transplant group: 46% ± 6% versus 32% ± 3%, respectively (P = .014). Non-relapse mortality (NRM) was significantly higher for the PBSC versus the BM group: 28% ± 2% versus 13% ± 4%, respectively (P = .004). In multivariate analysis, after adjustment for differences between both groups, the PBSC group was associated with a higher incidence of aGVHD (grade II-IV; hazard ratio [HR] = 2.33; P = .06), higher NRM (HR = 2.3; P = .015), and a decreased relapse incidence (HR, 0.61; P = .02) with no statistical difference of LFS between the 2 groups (P = .88). In conclusion, our results indicate significantly higher incidence of aGVHD and NRM and a lower incidence of relapse but not statistically different LFS comparing unrelated PBSC to BM grafts after RIC-alloSCT. [Copyright &y& Elsevier]
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- 2012
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28. Comparison of Matched Sibling, Unrelated and Haploidentical Donor Transplants Using Post-Transplant Cyclophosphamide in Patients with Acute Myeloid Leukemia, a Study of the ALWP EBMT.
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Sanz, Jaime, Galimard, Jacques-Emmanuel, Labopin, Myriam, Afanasyev, Boris, Angelucci, Emanuele, Ciceri, Fabio, Blaise, Didier, Cornelissen, Jan, Meijer, Ellen, Diez-Martin, José Luis, Koc, Yener, Rovira, Montserrat, Castagna, Luca, Savani, Bipin, Ruggeri, Annalisa, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia , *STEM cell transplantation , *INTERMEDIATE goods , *TRANSPLANTATION of organs, tissues, etc. , *BONE marrow cells , *TRANSPLANTING (Plant culture) - Abstract
The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. We retrospectively analysed outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n=215), MUD (n=235) and Haplo (n=789) donors registered in the EBMT database between 2010 and 2017. The median follow up period of the entire cohort was 2 years. Median age of patients was 52 years (range, 18-76), 693 (56%) were male and 928 (78%) were CMV seropositive. 47 (6%),543 (66%) and 239 (29%) had standard, intermediate and high risk cytogenetics, respectively. Peripheral blood (PB) was used in 814 (66%) patients and myeloablative conditioning (MAC) in 739 (59%). Compared to MSD and MUD, Haplo patients were older (p < 0.001), received more frequently MAC (p = 0.006), GvHD prophylaxis with PTCy combined with 2 other immunosuppressive drugs (p < 0.001) and bone marrow as stem cell source (p < 0.001). The cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and chronic extensive GVHD were 25% (95% CI 23-28), 9% (95% CI 7-10), 31% (95% CI 28-34) and 12% (95% CI 10-14), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality (NRM) and the probability of leukemia-free survival (LFS) and overall survival (OS) were 25% (95% CI 22-28), 19% (95% CI 17-21), 56% (95% CI 53-59) and 63% (95% CI 60-66), respectively. On multivariable analysis, Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no change in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of PB was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9). Variables associated with better LFS were MAC, good or intermediate risk cytogenetics and good performance status,while higher recipient´s age and positive CMV serostatus of the recipient showed worse outcome. The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD and Haplo is safe and effective and rates of GVHD are low, especially chronic. HLA mismatch in Haplo has a negative impact on acute GVHD and NRM in this setting but also offers increased anti-leukemic efficacy. As seen in other transplant scenarios, PB is associated with more GVHD and less relapse. [ABSTRACT FROM AUTHOR]
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- 2020
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29. Allogeneic Stem Cell Transplantation for AML Patients with RUNX1 Mutation in First Complete Remission: A Study on Behalf of the ALWP of the EBMT.
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Waidhauser, Johanna, Labopin, Myriam, Esteve, Jordi, Kröger, Nicolaus, Cornelissen, Jan, Gedde-Dahl, Tobias, Van Gorkom, Gwendolyn, Finke, Jürgen, Rovira, Montserrat, Schaap, Nicolaas, Petersen, Eefke, Beelen, Dietrich Wilhelm, Bunjes, Donald W., Schmid, Christoph, Nagler, Arnon, and Mohty, Mohamad
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STEM cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *KARYOTYPES , *MULTIVARIATE analysis , *UNIVARIATE analysis - Abstract
Acute myeloid leukemia bearing a RUNX1 gene mutation (RUNX1 + AML) has been proposed as a provisional entity in the 2016 WHO classification. Clinically, it has been associated with inferior response rates and outcome after conventional chemotherapy. Accordingly, RUNX1 + AML is allocated in the unfavorable prognostic category of the 2017 European Leukemia Net classification. Following allogeneic stem cell transplantation (alloSCT), RUNX1 was an unfavorable factor in one study in MDS/secondary AML, while data in de novo AML are scarce. Here, we present a retrospective study by the EBMT Acute Leukemia Working Party, aiming to elucidate the prognostic value of RUNX1 mutation in patients undergoing alloSCT for AML in first complete remission (CR1). Adults undergoing alloSCT for AML in CR1 from matched related or unrelated donors between 2013 and 2018 with complete information on conventional cytogenetics and RUNX1 mutational status were selected from the EBMT registry. Variables of interest were overall and leukemia-free survival (OS/LFS), GvHD/relapse free survival (GRFS), cumulative relapse incidence (RI), non-relapse mortality (NRM) and GvHD. Log rank test, Gray test and Cox regression models were used. 128 RUNX+ and 388 RUNX- patients were identified, >80% of both subgroups presenting as de novo AML. As expected, RUNX1+ patients rarely had co-mutations in NPM1 (6% vs. 26%, p=10−3), and showed a positive correlation with ASXL1 mutations (50% vs. 16%, p=10−4). Cytogenetic categories and other mutations (FLT3 -ITD, CEBPA) were equally distributed between the two groups, as were age, donor and graft type, CMV, conditioning and T cell depletion (TCD). Median follow-up was 16.4 (RUNX+) and 19.8 (RUNX-) months. 2y OS/LFS of the entire cohort were 64% [59-69]/57% [52-62], with no difference between RUNX1 + and RUNX1 - patients either in univariate or multivariate analysis (2y OS: 67.9% [57.3-78.5] vs. 63.1%v[57.4-68.7]p=0.15; 2y LFS: 57.6% [46.4-68.7] vs. 57% [51.4-62.6], p=0.38], figure 1). RUNX1 mutation neither had any impact among patients with normal karyotype (figure 2). Similarly, no other outcome parameter was influenced by RUNX1 mutational status. Instead, multivariate analysis revealed age and donor type as risk factors for OS, LFS and NRM. Poor cytogenetic was associated with higher RI and inferior LFS/GRFS, in vivo TCD with a lower rate of aGvHD II-IV, cGvHD, and better GRFS. Among patients with available information, FLT3 -ITD was an independent risk factor for relapse, LFS and GRFS. RUNX1 did not modify the role of FLT3 -ITD. Within the limits of a retrospective registry analysis, we could not find a negative influence of RUNX1 mutation on outcome after allogeneic SCT in CR1. Hence, transplantation in CR1 might overcome the unfavorable prognostic value of RUNX1 mutation and can be recommended as consolidation treatment in this entity. [ABSTRACT FROM AUTHOR]
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- 2020
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30. Allogeneic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia: In vivo T-Cell Depletion and Posttransplant Sorafenib Maintenance Improve Survival. A Retrospective Acute Leukemia Working Party-European Society for Blood and Marrow Transplant Study
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Sabine Gerull, Giorgia Battipaglia, Arnon Nagler, Johan Maertens, Patrice Chevallier, William Arcese, Jan J. Cornelissen, Mohamad Mohty, Azedine Djabali, Didier Blaise, Ali Bazarbachi, Joerg Halter, Jean El-Cheikh, Gérard Socié, Nicolaas Schaap, Edouard Forcade, Myriam Labopin, Jordi Esteve, Bazarbachi, Ali, Labopin, Myriam, Battipaglia, Giorgia, Djabali, Azedine, Forcade, Edouard, Arcese, William, Socié, Gerard, Blaise, Didier, Halter, Joerg, Gerull, Sabine, Cornelissen, Jan J, Chevallier, Patrice, Maertens, Johan, Schaap, Nicolaa, El-Cheikh, Jean, Esteve, Jordi, Nagler, Arnon, and Mohty, Mohamad
- Subjects
Oncology ,Sorafenib ,medicine.medical_specialty ,Acute leukemia ,Acute myeloid leukemia ,business.industry ,Incidence (epidemiology) ,lcsh:R ,Myeloid leukemia ,lcsh:Medicine ,Allogeneic stem cell transplantation ,Transplantation ,Bone transplantation ,In vivo ,Internal medicine ,hemic and lymphatic diseases ,medicine ,FLT3 mutation ,Stem cell ,In vivo T-cell depletion ,business ,medicine.drug - Abstract
Acute myeloid leukemia (AML) with FLT3-mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3-mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft versus host disease (GVHD) grades II-IV and III-IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, NPM1-mutation, transplantation in CR1, in vivo T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. In vivo T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care. ispartof: Clin Hematol Int vol:1 issue:1 pages:58-74 ispartof: location:United States status: Published online
- Published
- 2019
31. Allogeneic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Poor Karnofsky Performance Status Score. a Study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT).
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Saraceni, Francesco, Labopin, Myriam, Forcade, Edouard, Kroger, Nicolaus, Socié, Gerard, Niittyvuopio, Riitta, Cornelissen, Jan, Labussière-Wallet, Hélène, Blaise, Didier, Choi, Goda, Byrne, J., Guillerm, Gaelle, Lamy, Thierry, Esteve, Jordi, Bazarbachi, Ali, Savani, Bipin, Nagler, Arnon, and Mohty, Mohamad
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ACUTE myeloid leukemia , *KARNOFSKY Performance Status , *STEM cell transplantation , *CORD blood , *ALEMTUZUMAB , *ACUTE leukemia , *INTERMEDIATE goods , *CYTOGENETICS - Abstract
We report here the results of a retrospective study designed to evaluate outcome of patients with AML with KPS score ≤80% following allo-SCT. The analysis included adult AML patients undergoing allo-SCT in CR1 between 2000 and 2018, with a KPS score at the time of transplant between 50% and 80%. A total of 2,963 patients were identified. Median age at transplant was 55 years (18-77 years). The KPS score was 80% in 85% of the patients and <80% in 15% of the patients. Cytogenetic risk was good, intermediate or poor in 6%, 68% and 26% of the patients, respectively. Donor type was sibling (MSD), matched (10/10 UD), mismatched (9/10 UD) unrelated, haploidentical (haplo) or cord blood (CB) in 47%, 35%, 8%, 6% and 4% of patients. Conditioning was myeloablative (MAC) or reduced-intensity (RIC) in 42% and 58% of patients. Stem cell source was PBSC or BM in 84% and 14% of the patients, respectively. Cumulative incidence of grade II-IV acute GVHD (aGvHD) and chronic GVHD (cGvHD) was 26% and 38%, respectively. Non-relapse mortality (NRM) and relapse incidence (RI) at 2 years were 19% and 27%. Leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) rates were 54%, 59% and 41%, respectively. On multivariate analysis, transplant from a MSD was associated with a reduced risk of aGvHD (10/10 UD HR 1.8, 9/10 UD HR 2.4, haplo HR 1.9, CB HR 3.4, p<10−4) and NRM (10/10 UD HR 1.4, 9/10 UD HR 2.4, haplo HR 1.8, CB HR 2, p<10−3, MSD as reference) as compared to all other donor types. Patients with KPS score of 80% had significantly lower NRM and improved survival as compared to patients with KPS<80%. Other factors independently associated with improved OS were younger age, female sex, good or intermediate risk cytogenetics and de-novo AML. In order to compare outcome following MAC and RIC conditioning regimens the analysis was restricted to patients receiving transplant from MSD or UD. Patients with a KPS score of 80% or <80% were analyzed separately. In the group of patients with a KPS score of 80%, a RIC regimen was associated with higher RI (HR 1.4, p<0.01), higher incidence of severe cGVHD (HR 1.6, p<0.001), and inferior GRFS (HR 1.3, p<0.001) as compared to MAC. NRM was not significantly different following RIC or MAC in this population. In contrast, in patients with a KPS score <80%, RIC was associated with lower NRM (HR 0.3, p<0.0001) and better LFS (HR 0.6, p<0.01), OS (HR 0.5, p<0.0001) and GRFS (HR 0.6, p<0.01) as compared to MAC. In conclusion, allo-SCT is feasible in patients with acute myeloid leukemia in first remission and KPS score ≤80%, with acceptable NRM and survival rates. In patients with a KPS score of 80% a MAC regimen was associated with lower relapse rate, similar NRM and better GRFS as compared to RIC, while in patients with a KPS score <80% RIC was associated with reduced NRM and improved OS. In addition, transplant from a MSD was associated with reduced risk of NRM and aGVHD rates as compared to other donor types. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. 18 - Outcomes of Allogeneic Hematopoietic Cell Transplantation for AML with Complex Karyotypes: A Retrospective Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and MD Anderson Cancer Center.
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Ciurea, Stefan O., Labopin, Myriam, Polge, Emmanuelle, Kongtim, Piyanuch, Rondon, Gabriela, Socié, Gerard, Volin, Liisa, Passweg, Jakob, Chevallier, Patrice, Beelen, Dietrich W., Milpied, Noel, Blaise, Didier, Cornelissen, Jan, Fegueux, Nathalie, Mohty, Mohamad, Savani, Bipin N., Champlin, Richard E., and Nagler, Arnon
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HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia , *KARYOTYPES , *MEDICAL centers , *BONE marrow transplantation - Published
- 2017
- Full Text
- View/download PDF
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