24 results on '"Cornelissen, Jan"'
Search Results
2. 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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3. 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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4. Exploratory Study of Predicted Indirectly ReCognizable HLA Epitopes in Mismatched Hematopoietic Cell Transplantations.
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Geneugelijk, Kirsten, Thus, Kirsten A., van Deutekom, Hanneke W. M., Calis, Jorg J. A., Borst, Eric, Keşmir, Can, Oudshoorn, Machteld, van der Holt, Bronno, Meijer, Ellen, Zeerleder, Sacha, de Groot, Marco R., von dem Borne, Peter A., Schaap, Nicolaas, Cornelissen, Jan, Kuball, Jürgen, and Spierings, Eric
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HEMATOPOIETIC stem cell transplantation ,HLA histocompatibility antigens ,COMPUTATIONAL biology ,ORGAN donors ,GRAFT versus host disease - Abstract
HLA-mismatches in hematopoietic stem-cell transplantation are associated with an impaired overall survival (OS). The aim of this study is to explore whether the Predicted Indirectly ReCognizable HLA-Epitopes (PIRCHE) algorithm can be used to identify HLA-mismatches that are related to an impaired transplant outcome. PIRCHE are computationally predicted peptides derived from the patient's mismatched-HLA molecules that can be presented by donor-patient shared HLA. We retrospectively scored PIRCHE numbers either presented on HLA class-I (PIRCHE-I) or class-II (PIRCHE-II) for a Dutch multicenter cohort of 103 patients who received a single HLA-mismatched (9/10) unrelated donor transplant in an early phase of their disease. These patients were divided into low and high PIRCHE-I and PIRCHE-II groups, based on their PIRCHE scores, and compared using multivariate statistical analysis methods. The high PIRCHE-II group had a significantly impaired OS compared to the low PIRCHE-II group and the 10/10 reference group (HR: 1.86, 95%-CI: 1.02–3.40; and HR: 2.65, 95%-CI: 1.53–4.60, respectively). Overall, PIRCHE-II seem to have a more prominent effect on OS than PIRCHE-I. This impaired OS is probably due to an increased risk for severe acute graft-vs.-host disease. These data suggest that high PIRCHE-II scores may be used to identify non-permissible HLA mismatches within single HLA-mismatched hematopoietic stem-cell transplantations. [ABSTRACT FROM AUTHOR]
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- 2019
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5. Anti‐thymocyte globulin for graft‐versus‐host disease prophylaxis in patients with intermediate‐ or high‐risk acute myeloid leukaemia undergoing reduced‐intensity conditioning allogeneic stem cell transplantation in first complete remission – a survey on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation
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Ofran, Yishai, Beohou, Eric, Labopin, Myriam, Blaise, Didier, Cornelissen, Jan J., Groot, Marco R., Socié, Gerard, Huynh, Anne, Maertens, Johan, Baron, Frederic, Mohty, Mohamad, and Nagler, Arnon
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ALEMTUZUMAB ,STEM cell transplantation ,GRAFT versus host disease ,BONE marrow ,GLOBULINS ,INSTITUTIONAL review boards - Abstract
The article offers information on a study related to anti-thymocyte globulin for graft-versus-host disease prophylaxis in patients with intermediate- or high-risk acute myeloid leukaemia undergoing reduced-intensity conditioning allogeneic stem cell transplantation in first complete remission. It notes that the survey was conducted by Acute Leukaemia Working Party of European Society for Blood and Marrow Transplantation.
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- 2019
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6. The feasibility and efficacy of subcutaneous plerixafor for mobilization of peripheral blood stem cells in allogeneic HLA–identical sibling donors: results of the HOVON‐107 study.
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Greef, Georgine E., Braakman, Eric, Holt, Bronno, Janssen, Jeroen J.W.M., Petersen, Eefke, Vucinic, Vladimir, Thuss, Nicole, Grootes, Meriam, and Cornelissen, Jan J.
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HEMATOPOIETIC stem cell transplantation ,STEM cells ,HOMOGRAFTS ,ORGAN donors ,GRAFT versus host disease - Abstract
Background: Plerixafor (PFX) mobilizes CD34+ cells into circulation by disrupting the CXCR4 binding of the hematopoietic stem cell in its bone marrow niche. Study design and Methods: in the prospective HOVON‐107 study (www.hovon.nl) 23 allogeneic HLA–identical sibling donors received one or two subcutaneous (sc) injections of plerixafor 0.320 mg/kg.The primary endpoint, was defined as feasibility to mobilize a minimum of 2.0 x106 CD34+ cells/kg recipient weight obtained by leukopheresis in at least 90% of the donors. Results: median 3.3 x 106 CD34+ cells/kg (1.9‐6.5) were collected after 1 (n=12) or 2 (n=10) sc injections of PFX. Side effects occurred in 15/23 (65%) donors: most were grade 1‐2; in 5 donors grade 3 and all resolved. All grafts were directly transplanted. Compared to 10 grafts obtained with G‐CSF the number of CD34+ cells was 2.4 fold lower but the percentage of phenotypically most immature CD34+ subset was higher (31% vs 15%). The total number of CD3+ cells in the graft seemed higher after PFX‐mobilization, but CD4/CD 8 ratios, and frequencies of Th2, Th17 and regulatory T‐cells or NK cells were comparable. All patients engrafted and no increase in incidence or severity of acute or chronic graft versus host disease was observed. Conclusion: stem cell mobilization with sc PFX 0.320 mg/kg in allogeneic sibling donors is feasible with limited toxicity for donors. 14 allogeneic donors were mobilized with PFX 0.320 mg intravenously according to the same protocol. Due to the limited numbers, these results are in the supplementary section. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Anti-thymocyte globulin improves survival free from relapse and graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in patients with Philadelphia-negative acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the EBMT.
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Czerw, Tomasz, Labopin, Myriam, Giebel, Sebastian, Socié, Gérard, Volin, Liisa, Fegueux, Nathalie, Masszi, Tamás, Blaise, Didier, Chaganti, Sridhar, Cornelissen, Jan J., Passweg, Jakob, Maertens, Johan, Itälä‐Remes, Maija, Wu, Depei, Mohty, Mohamad, Nagler, Arnon, and Itälä-Remes, Maija
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GENETIC polymorphisms ,BONE marrow ,GRAFT versus host disease ,GLOBULINS ,LYMPHOBLASTIC leukemia - Abstract
Background: Mobilized peripheral blood stem cells are currently the predominant source of grafts for allogeneic transplantation (allogeneic peripheral blood stem cell transplantation [allo-PBSCT]), although, in comparison with bone marrow, their use is associated with an increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen.Methods: The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL). The primary endpoint was survival free from relapse, grade 3 to 4 acute graft-versus-host disease (aGVHD), and cGVHD (ie, graft-versus-host disease-free/relapse-free survival [GRFS]). Nine-hundred twenty-four patients who underwent unmanipulated allo-PBSCT in their first complete remission between 2007 and 2016 were included. ATG was used in 97 of the 494 transplants from matched sibling donors (20%) and in 307 of the 430 transplants from human leukocyte antigen-matched (8 of 8 loci) unrelated donors (71%).Results: The use of ATG was an independent factor for an improved chance of GRFS (hazard ratio [HR], 0.70; P = .0009). Furthermore, it was associated with a reduced risk of both grade 2 to 4 (HR, 0.66; P = .005) and grade 3 to 4 aGVHD (HR, 0.58; P = .03). Similarly, its addition reduced the incidence of both total (HR, 0.45; P < 10-5 ) and extensive cGVHD (HR, 0.30; P < 10-5 ) as well as nonrelapse mortality (HR, 0.58; P = .01). No significant effect was found with respect to leukemia-free or overall survival. However, an increased risk of relapse was noted for those who received ATG (HR, 1.40; P = .04).Conclusions: Patients with Ph-neg ALL treated with allo-PBSCT benefit from the use of ATG in terms of improved GRFS. Its use may, therefore, be considered in this setting. Cancer 2018;124:2523-33. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]- Published
- 2018
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8. 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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9. 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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10. 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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11. 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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12. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
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Symeonidis, Argiris, Biezen, Anja, Wreede, Liesbeth, Piciocchi, Alfonso, Finke, Juergen, Beelen, Dietrich, Bornhäuser, Martin, Cornelissen, Jan, Volin, Liisa, Mufti, Ghulam, Chalandon, Yves, Ganser, Arnold, Bruno, Benedetto, Niederwieser, Dietger, Kobbe, Guido, Schwerdtfeger, Rainer, Witte, Theo, Robin, Marie, and Kröger, Nicolaus
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GRAFT versus host disease ,STEM cell transplantation research ,LEUKEMIA ,PROGNOSIS ,MYELODYSPLASTIC syndromes - Abstract
The results of allogeneic stem cell transplantation (allo- SCT) in chronic myelomonocytic leukaemia ( CMML) are usually reported together with other categories of myelodysplastic syndrome. We analysed transplantation outcome in 513 patients with CMML, with a median age of 53 years reported to the European Group for Blood and Marrow Transplantation. Conditioning was standard ( n = 249) or reduced-intensity ( n = 226). Donors were human leucocyte antigen-related ( n = 285) or unrelated ( n = 228). Disease status at transplantation was complete remission ( CR) in 122 patients, no CR in 344, and unknown in 47. Engraftment was successful in 95%. Grades 2-4 acute graft- versus-host disease (Gv HD) occurred in 33% of the patients and chronic Gv HD was reported in 24%. The 4-year cumulative incidence of non-relapse mortality was 41% and 32% for relapse, resulting in a 4-year estimated relapse-free and overall survival (OS) of 27% and 33%, respectively. Patients transplanted in CR had lower probability for non-relapse death ( P = 0·002) and longer relapse-free and OS ( P = 0·001 and P = 0·005, respectively). In multivariate analysis the only significant prognostic factor for survival was the presence of CR at transplantation ( P = 0·005). Allo- SCT remains a curative treatment option for patients with CMML and should preferably be performed early after diagnosis or after establishing the best possible remission status. [ABSTRACT FROM AUTHOR]
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- 2015
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13. Antithymocyteglobulin as prophylaxis of graft failure and graft-versus-host disease in recipients of partially T-cell—depleted grafts from matched unrelated donors: A dose-finding study
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Meijer, Ellen, Cornelissen, Jan J., Löwenberg, Bob, and Verdonck, Leo F.
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GRAFT rejection , *DENTAL prophylaxis , *GRAFT versus host disease , *T cells - Abstract
: ObjectiveIn this study, we set out to evaluate the effect of three different antithymocyteglobulin (ATG) doses on graft failure and incidence of graft-vs-host disease (GVHD) among recipients of partially T-cell–depleted (TCD) grafts from matched unrelated donors (MUDs).: Patients and MethodsData of 74 consecutively treated MUD recipients were analyzed. Fifty-two, 13, and 9 MUD patients were treated with ATG in a total dose of 8 mg/kg, 6 mg/kg, and 4 mg/kg (given from days −8 until −4), respectively.: ResultsGranulocyte and platelet engraftment were not different between the groups, while graft failure was observed in two patients only (receiving 8 mg/kg and 4 mg/kg ATG, respectively). The cumulative incidence of severe (grade III-IV) acute GVHD and extensive chronic GVHD was 4%, 0%, 44% and 11%, 8%, 44% in groups receiving ATG in a dose of 8 mg/kg, 6 mg/kg, and 4 mg/kg, respectively (severe acute GVHD: p<0.001; extensive chronic GVHD: p = 0.05).: ConclusionBased on these findings, we recommend when ATG is used in the setting of stem cell transplantation with (partially) TCD grafts from MUDs, to give a total dose of 6 to 8 mg/kg. A further decrease in dosage resulted in a highly significant increased incidence of severe acute and extensive chronic GVHD. [Copyright &y& Elsevier]
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- 2003
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14. A randomized multicenter comparison of CD34+-selected progenitor cells from blood vs from bone marrow in recipients of HLA-identical allogeneic transplants for hematological malignancies
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Cornelissen, Jan J., van der Holt, Bronno, Petersen, Eefke J., Vindelov, Lars, Russel, Charlotte A., Höglund, Martin, Maertens, Johan, Schouten, Harry C., Braakman, Eric, Steijaert, Monique M.C., Zijlmans, Mark J.M., Slaper-Cortenbach, Ineke, Boogaerts, Marc A., Löwenberg, Bob, and Verdonck, Leo F.
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BLOOD cells , *HEMATOPOIETIC stem cells , *HOMOGRAFTS , *GRAFT versus host disease - Abstract
Objective. Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34+ selection for T-cell depletion (TCD) in both study arms.Patients and Methods. Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms.Results. Recipients of PBPC received more CD3+ T cells (median: 3.0 vs 2.0×105/kg, p<0.0001) and more CD34+ cells (median: 3.6 vs 0.9×106/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II–IV was 37% after BMT vs 52% after PBPCT and was most significantly (p = 0.007) affected by the number of CD3+ T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34+ cells were associated with less TRM. With a median follow-up of 37 months (range: 12–75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT (p = 0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2×105/kg.Conclusion. Outcome following T cell–depleted PBPCT critically depends on the number of CD3+ T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34+ cell numbers. [Copyright &y& Elsevier]
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- 2003
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15. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT.
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Ruggeri, Annalisa, Labopin, Myriam, Bacigalupo, Andrea, Afanasyev, Boris, Cornelissen, Jan J., Elmaagacli, Ahmet, Itälä-Remes, Maija, Blaise, Didier, Meijer, Ellen, Koc, Yener, Milpied, Noel, Schouten, Harry C., Kroeger, Nicolaus, Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation ,ACUTE leukemia ,HEMATOPOIETIC stem cell transplantation ,GRAFT versus host disease ,CELL transplantation ,LEUKEMIA treatment - Abstract
Background: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis. Seventy-eight patients received PT-Cy alone (group 1); 204 received PT-Cy in combination with one IS drug—cyclosporine-A (CSA) or methotrexate (MTX) or mycophenolate-mofetil (MMF) (group 2), while 141 patients received PT-Cy in combination with two IS drugs—CSA + MTX or CSA + MMF (group 3). Transplants were performed from 2007 to 2015 and median follow-up was 20 months. Results: Probability of overall survival (OS) at 2 years was 50, 52.2, and 62.4%, for the three groups, respectively,
p = 0.06. In multivariate analysis, in comparison to PT-Cy alone, the addition of two IS drugs was associated with reduced risk of extensive cGVHD (HR 0.25,p = 0.02). Use of bone marrow (BM) and anti-thymocyte globulin were independently associated with reduced risk of extensive cGVHD. Prognostic factors for non-relapse mortality (NRM) were the addition of two IS drugs to PT-Cy (HR 0.35,p = 0.04), diagnosis of AML, disease status at transplant, and patient CMV serology. Factors associated with increased OS were the use of PT-Cy with two IS drugs (HR 0.49,p = 0.02), AML, and disease status at transplant. Conclusion: For GVHD prophylaxis in MSD and UD HSCT, the addition of IS drugs to PT-Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving survival. [ABSTRACT FROM AUTHOR]- Published
- 2018
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16. 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]
- Published
- 2014
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17. 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]
- Published
- 2020
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18. HLA-Mismatched Donors in Patients with Myelodysplastic Syndrome: An EBMT Registry Analysis.
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Robin, Marie, Porcher, Raphaël, Ruggeri, Annalisa, Blaise, Didier, Wolschke, Christine, Koster, Linda, Angelucci, Emanuele, Stölzel, Friedrich, Potter, Victoria, Yakoub-Agha, Ibrahim, Koc, Yener, Ciceri, Fabio, Finke, Jürgen, Labussière-Wallet, Hélène, Cascon, Maria Jesús Pascual, Verbeek, Mareike, Rambaldi, Alessandro, Cornelissen, Jan J., Chevallier, Patrice, and Radia, Rohini
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MYELODYSPLASTIC syndromes , *BLOOD donors , *GRAFT versus host disease , *CYCLOPHOSPHAMIDE , *BONE marrow transplantation - Abstract
Highlights • Overall survival, progression-free survival, and nonrelapse mortality were better in haploidentical than in cord blood donors. • Nonrelapse mortality was not significantly different between haploidentical and mismatched unrelated donor. • Relapse risk was not influenced by the type of donor. • Acute graft-versus-host disease risk was lower with haploidentical or cord blood donors than with mismatched unrelated donors. • Chronic graft-versus-host disease was not influenced by the type of donor. Abstract Recently, haploidentical transplantation (haplo) using post-transplant cyclophosphamide (PTCy) has been reported to give very encouraging results in patients with hematological malignancies. Patients who have no HLA-matched donor currently have the choice between a mismatched unrelated donor, an unrelated cord blood (CB) donor, and a haploidentical related donor. The aim of our study is to compare the outcome of patients with myelodysplastic syndrome (MDS) who have been transplanted from a haploidentical donor using PTCy, an HLA-mismatched unrelated donor (marrow or peripheral blood stem cells), or an unrelated mismatched CB donor. A total of 833 MDS patients from the European Group for Blood and Marrow Transplantation (EBMT) registry, transplanted between 2011 and 2016, were identified. The potential benefit of haplo was compared with mismatched unrelated and CB donors in an adjusted and weighted model taking into account potential confounders and other prognostic variables. Haplo was at lower risk of acute graft-versus-host disease (GVHD) than mismatched unrelated donor (P =.010) but at similar risk than CB. Progression-free survival was better after haplo (versus mismatched unrelated, P =.056; versus CB, P =.003) and overall survival tended to be superior after haplo (versus mismatched unrelated, P =.082; versus CB, P =.002). Nonrelapse mortality was not significantly different between haplo and mismatched unrelated donors. Relapse risk was not influenced by the type of donor. In conclusion, patients with MDS from the EBMT registry receiving hematopoietic stem cell transplantation from a haplo donor have significantly better outcome than those receiving hematopoietic stem cell transplantation from a CB donor and at least similar or better outcome than with a mismatched unrelated donor. Prospective studies comparing the type of donors will be needed to confirm this assumption. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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19. Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality.
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Shouval, Roni, De Jong, Cornelis N., Fein, Joshua, Broers, Annoek E.c., Danylesko, Ivetta, Shimoni, Avichai, Reurs, Marloes R., Baars, Adája E., Van Der Schaft, Niels, Nagler, Arnon, and Cornelissen, Jan J.
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GRAFT versus host disease , *ALBUMINS , *HEMATOPOIETIC stem cell transplantation , *COMORBIDITY , *BIOLOGICAL tags , *RISK assessment , *PROGNOSIS , *PATIENTS , *THERAPEUTICS - Abstract
Biomarkers measured in blood chemistry before allogeneic hematopoietic stem cell transplantation (HSCT) may reflect patients' physiological status. We hypothesized that selected markers are predictive for nonrelapse mortality (NRM) following transplantation and could contribute to risk assessment. We investigated the value of pre-HSCT albumin, estimated glomerular filtration rate (eGFR), and alkaline phosphatase (AlkP) in predicting NRM. We retrospectively analyzed clinical and laboratory data from 1217 patients receiving a first HSCT in 2 European centers between 2003 and 2015. Transplantation indications and conditioning regimens were diverse. Patients had a median age of 55 years and hematopoietic cell transplantation comorbidity index (HCT-CI) scores of 0 (24%), 1 to 2 (39%), and ≥3 (37%). Cutoffs of eGFR <60 mL/min, albumin <3.5 g/dL, and AlkP >180 IU/L corresponded with 8.8%, 8.3%, and 6.5% of the patients, respectively. eGFR and albumin were associated with increased risk and higher cumulative incidence of day-100, 1-year, and 2-year NRM, both as continuous or categorized variables. A similar pattern was observed for AlkP, except for day-100 NRM. In multivariable analyses, eGFR and albumin were consistently among the top risk factors for early and late-term NRM, abrogating the role of age. Prediction models for day-100, 1-year, and 2-year NRM based only on HCT-CI resulted in c-statistics of .565, .575, and .577, respectively. Addition of both biomarkers increased c-statistics for day-100, 1-year, and 2-year NRM to .651, .633, and .624, respectively. Albumin and eGFR are prognostic biomarkers for NRM after HSCT and improve the discriminative power of the HCT-CI. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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20. 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]
- Published
- 2015
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21. Double Umbilical Cord Blood Transplantation: A Study of Early Engraftment Kinetics in Leukocyte Subsets using HLA-Specific Monoclonal Antibodies
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Somers, Judith A.E., Brand, Anneke, van Hensbergen, Yvette, Mulder, Arend, Oudshoorn, Machteld, Sintnicolaas, Kees, Gratama, Jan-Willem, Falkenburg, J.H. Frederik, Braakman, Eric, and Cornelissen, Jan J.
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CORD blood transplantation , *LEUCOCYTES , *HLA histocompatibility antigens , *MONOCLONAL antibodies , *FLOW cytometry , *GRAFT versus host disease , *GRAFT rejection - Abstract
Abstract: Single cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the different leukocyte subsets and the mechanism of graft predominance is largely unknown. To investigate whether a differential engraftment might reveal a specific subset that could play a key role in the mechanism of graft predominance, we studied early engraftment kinetics of different leukocyte subpopulations by flow cytometry using human monoclonal antigen–specific human leukocyte antigen antibodies, directed against mismatched human leukocyte antigen-A or –B antigens between recipient and CBUs. Twenty-two patients, who had received a double UCBT preceded by a reduced-intensity conditioning regimen, were evaluated at days +11, +18, +25, and +32 posttransplantation. Single CBU predominance in the various leukocyte subsets was established within 18 days posttransplantation. CD4+ T cells of the dominant CBU showed early peripheral blood expansion. Moreover, chimerism in CD4+ and CD8+ T cell and natural killer cell subsets at day +11 was predictive of ultimate graft predominance. These findings show that engraftment kinetics of the various leukocyte subsets vary considerably after double UCBT and may suggest an important role for CD4+ T cells in a presumed alloreactive graft-versus-graft rejection. [Copyright &y& Elsevier]
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- 2013
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22. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation.
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Schmid, Christoph, Labopin, Myriam, Nagler, Arnon, Niederwieser, Dietger, Castagna, Luca, Tabrizi, Reza, Stadler, Michael, Kuball, Jurgen, Cornelissen, Jan, Vorlicek, Jiri, Socié, Gerard, Falda, Michele, Vindeløv, Lars, Ljungman, Per, Jackson, Graham, Kroger, Nicolaus, Rank, Andreas, Polge, Emmanuelle, Rocha, Vanderson, and Mohty, Mohamad
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ACUTE myeloid leukemia treatment , *HEMATOPOIETIC stem cell transplantation , *RETROSPECTIVE studies , *DISEASE relapse , *LYMPHOCYTES , *GRAFT versus host disease - Abstract
Because information on management and outcome of AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC transplants performed for AML in complete remission (CR) between 1999 and 2008, cumulative incidence of relapse was 32% ± 1%. Relapsed patients (263) were included into a detailed analysis of risk factors for overall survival (OS) and building of a prognostic score. CR was reinduced in 32%; remission duration after transplantation was the only prognostic factor for response (P = .003). Estimated 2-year OS from relapse was 14%, thereby resembling results of AML relapse after standard conditioning. Among variables available at the time of relapse, remission after HSCT> 5 months (hazard ratio [HR] = 0.50, 95% confidence interval [Cl], 0.37-0.67, P < .001), bone marrow blasts less than 27% (HR = 0.53, 95% Cl, 0.40-0.72, P < .001), and absence of acute GVHD after HSCT (HR = 0.67, 95% Cl, 0.49-0.93, P = .017) were associated with better OS. Based on these factors, 3 prognostic groups could be discriminated, showing OS of 32% ± 7%, 19% ± 4%, and 4% ± 2% at 2 years (P < .0001). Long-term survival was achieved almost exclusively after successful induction of CR by cytoreductive therapy, followed either by donor lymphocyte infusion or second HSCT for consolidation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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23. Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia Following Total Body Irradiation- the Effect of Anti- Thymocyte Globulin on Transplant Outcome: ALWP of the EBMT Study.
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Nagler, Arnon, Labopin, Myriam, Niittyvuopio, Riitta, Maertens, Johan, Poiré, Xavier, Cornelissen, Jan, Remenyi, Peter, Bourhis, Jean Henri, Beguin, Yves, Craddock, Charles, Kerre, Tessa, Schroyens, Wilfried, Savani, Bipin, and Mohty, Mohamad
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GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia treatment , *TOTAL body irradiation , *THYMOCYTES , *GLOBULINS - Abstract
Background Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HSCT). Previous studies have shown that anti- thymocyte globulin (ATG) reduce the incidence of acute and or chronic GVHD after reduced intensity and chemotherapy based myeloablative conditioning regimen pre-HSCT. The impact of the use of ATG following TBI based myeloablative conditioning regimen has been poorly explored. Recent prospective, double-blind phase III study of ATG vs placebo in patients (pts) with MDS or AML following myeloablative conditioning report inferior progression-free survival (PFS) and overall survival (OS) in the ATG arm, especially in the TBI cohort. However, this study includes only small and quite heterogeneous sub-populations within the TBI group. We therefore assessed the effect of ATG in a large homogenous cohort of AML pts undergoing HSCT with TBI and reported to the ALWP of the EBMT. Methods The study included 724 AML pts that underwent HSCT during the years 2008-2016 from a matched sibling (n=412) or 9-10 unrelated donor (n=312), following TBI (>8Gy) based conditioning regimen. All disease statuses were included (CR1=489, CR2=148; refractor=87). Graft source was PB in the majority of pts (n=579, 80%). 251 pts received ATG while 473 did not. Median follow up was 58.8 (28-83) months. The disease and transplant characteristics were similar in both groups except for type of donors, unrelated donor HSCT received ATG in 89% vs 19% in sibling donor HSCT (p<10−4). Conditioning was TBI-Cy in 84.5% and 93.5% and TBI-Flu in 15.5% and 6.5% of the pts, respectively. GVHD prophylaxis was CSA in combination with MTX in 72.5% and 74.2% of the pts, respectively. Results In univariate analysis, day 100 incidence of acute GVHD II-IV and III-VI was 24.1% vs 33% (p<0.01) and 7% vs 13% (p<0.01) for pts receiving ATG vs no ATG, respectively. 2y total and severe chronic GVHD incidence was 34.3% vs 46.2% (p=0.003) and 16.4% vs 22.3% (p=0.015), respectively. Incidence of infectious complications leading to death did not differ between the ATG and no ATG groups, 14.1% and 11.2% (p=NS), respectively. In multivariate analysis, ATG incorporation as part of TBI based conditioning regimen resulted in a significant reduction in grade II-IV and III-IV acute GVHD incidence (HR 0.28, p<10-4 and HR -0.21, p<10-4, respectively). Similarly, ATG administration resulted in a significant reduction in chronic GVHD and transplant related mortality (TRM) HR-0.63, p=0.02 and HR-0.546, p=0.02, respectively. Finally, relapse incidence, LFS, OS and GVHD free relapse free survival (GRFS) did not differ between the groups. Conclusions The addition of ATG to TBI based conditioning regimen followed by HSCT for AML results in significant reduction of acute and chronic GVHD, translating into a significant reduction in TRM without increasing relapse rate, and a similar LFS or OS. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. 85 - Impact of ABO-Mismatching Following HLA- Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for AML—a Report From the ALWP of the EBMT.
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Savani, Bipin N., Labopin, Myriam, Canaani, Jonathan, Michallet, Mauricette, Craddock, Charles, Socié, Gerard, Volin, Liisa, Maertens, Johan A., Crawley, Charles, Blaise, Didier, Ljungman, Per T., Cornelissen, Jan, Russell, Nigel, Baron, Frédéric, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Schmid, Christoph, Giebel, Sebastian, and Mohty, Mohamad
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GRAFT versus host disease , *HEMATOPOIETIC stem cell transplantation , *HLA histocompatibility antigens , *BLOOD donors , *PROGRESSION-free survival , *THERAPEUTICS - Published
- 2017
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