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Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study
Greinix, H. T., Eikema, D. J., Koster, L., Penack, O., Yakoub-Agha, I., Montoto, S., Chabannon, C., Styczynski, J., Nagler, A., Robin, M., et al
Haematologica. 2021
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Editor's Choice
Abstract
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome after allogeneic hematopoietic cell transplantation. Advances in prophylaxis and supportive care have taken place over the years. The aim of this study is to test whether incidence and mortality of aGvHD have been reduced over time. 102 557 patients with a median age of 47.6 years with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015. Findings: 100-day-incidences of aGvHD grades II-IV decreased from 40%, to 38%, 32%, 29% and 28% over calendar time (p.
PICO Summary
Population
Patients undergoing first allogeneic sibling or unrelated donor transplant (URD) between 1990 and 2015 (n=102 557)
Intervention
Registry data study assessing incidence of acute GvHD (aGvHD)
Comparison
Patients were compared in the following time periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015
Outcome
In multivariate analysis URD, not in CR at transplant or untreated, and female donor for male recipient were associated with increased risk whereas use of ATG/alemtuzumab decreased aGvHD incidence. Median follow-up was 214, 169, 127, 81 and 30 months for periods analyzed. 3-year-survival after aGvHD grades II-IV increased significantly from 38% to 40%, 43%, 44%, and 45%. In multivariate analysis URD, not in CR at transplant, peripheral blood as stem cell source, female donor for male recipient, and use of ATG/alemtuzumab were associated with increased mortality whereas reduced-intensity conditioning with lower one. Mortality increased with increasing patients‘ age but decreased in the recent cohorts.
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Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT
Gilleece, M. H., Shimoni, A., Labopin, M., Robinson, S., Beelen, D., Socié, G., Unal, A., Ganser, A., Vitek, A., Sengeloev, H., et al
Blood cancer journal. 2021;11(5):88
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Editor's Choice
Abstract
Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006-2016 from human leukocyte antigen (HLA) matched siblings (n?=?719) or HLA 10/10 matched unrelated donors (n?=?293). Conditioning was myeloablative (n?=?610) or reduced-intensity (n?=?432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P?0.001). Two-year relapse rates were 24% (95% CI, 21-28) and 40% (95% CI, 34-46) in MRD NEG and MRD POS groups (P?0.001), respectively. Leukemia-free survival (LFS) was 57% (53-61) and 46% (40-52%), respectively (P?=?0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
PICO Summary
Population
Patients with AML who were transplanted in second complete remission (CR2) at transplant (n=1042)
Intervention
Patients who were minimal disease negative (MRD NEG, n=749)
Comparison
Patients who were minimal disease positive (MRD POS, n=293)
Outcome
Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months). Two-year relapse rates were 24% and 40% in MRD NEG and MRD POS groups, respectively. Leukemia-free survival (LFS) was 57% and 46%, respectively, but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
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Nonmyeloablative Alternative Donor Transplantation for Hodgkin and Non-Hodgkin Lymphoma: From the LWP-EBMT, Eurocord, and CIBMTR
Fatobene, G., Rocha, V., St Martin, A., Hamadani, M., Robinson, S., Bashey, A., Boumendil, A., Brunstein, C., Castagna, L., Dominietto, A., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco1902408
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Editor's Choice
Abstract
PURPOSE To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation. PATIENTS AND METHODS We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide. RESULTS Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively). CONCLUSION When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.
PICO Summary
Population
patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received alternative donor transplantations from 2009 to 2016 (n=740)
Intervention
Haploidentical transplantation from bone marrow or peripheral blood (n=526)
Comparison
Unrelated cord blood transplantation (UCB, n=214)
Outcome
Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55 and HR, 1.5, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; and HR, 1.86), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91 and HR, 2.27 respectively).
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Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma - a LWP-EBMT study
Bazarbachi, A., Boumendil, A., Finel, H., Castagna, L., Dominietto, A., Blaise, D., Diez-Martin, J. L., Tischer, J., Gulbas, Z., Wallet, H. L., et al
British journal of haematology. 2019
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Editor's Choice
Abstract
Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.
PICO Summary
Population
Adults with lymphoma (n=474) : Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29)
Intervention
Haploidentical transplant with post-transplant cyclophosphamide
Comparison
None
Outcome
On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival was better for FL, HL and PTCL, whereas overall survival was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status.
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Impact of t-cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the european blood and marrow transplant (ebmt) saa working party
Samarasinghe, S., Clesham, K., Iacobelli, S., Sbianchi, G., Knol, C., Hamladji, R. M., Socie, G., Aljurf, M., Koh, M., Sengeloev, H., et al
American journal of hematology. 2018
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Editor's Choice
Abstract
We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) haemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either ATG (n=1283), alemtuzumab (n=261) or no serotherapy (NS) (n=293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared to no serotherapy (p=0.021 and p=0.003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared to ATG (P=0.012) and no serotherapy (p < 0.001). By multivariate analysis, when compared to ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; p<0.001) and chronic GVHD (HR 0.58; 95% CI 0.35 - 0.94; p=0.027). OS was significantly better in ATG and alemtuzumab patients compared with no serotherapy (p=0.010 and p=0.025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared to ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA. This article is protected by copyright. All rights reserved.