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Haploidentical versus matched unrelated donor transplants using post-transplant cyclophosphamide for lymphomas
Mussetti, A., Kanate, A. S., Wang, T., He, M., Hamadani, M., Sr, H. F., Boumendil, A., Sr., Glass, B., Castagna, L., Dominietto, A., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND when using post-transplant cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available. OBJECTIVE In this study we wanted to test if using a haploidentical donor has the same results of a MUD. STUDY DESIGN a total of 2140 adults (34% CIBMTR, 66% EBMT registry) aged ≥18 years who received their first haploidentical hematopoietic cell transplant (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010-2019 were retrospectively analyzed. RESULTS The majority of both MUD and haploidentical HCTs received reduced intensity/non-myeloablative conditioning (74% and 77%, respectively), used a peripheral blood stem cell graft (91% and 60%, respectively) and a three-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (HR=1.69, 95%CI=1.30-2.27, p<0.001), progression-free survival (HR=1.39, 95%CI=1.10 - 1.79, p=0.008), non-relapse mortality (HR=1.93, 95% CI=1.21 - 3.07, p=0.006), platelets engraftment (HR=0.69, 95%CI=0.59 - 0.80, p<0.001), acute grade 2-4 GVHD incidence (HR=1.65, 95%CI=1.28 - 2.14, p<0.001) and chronic GVHD (HR=1.79, 95%CI=1.30 - 2.48, p<0.001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results. CONCLUSION whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma.
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Risk factors and outcomes of follicular lymphoma after allogeneic hematopoietic stem cell transplantation using HLA-matched sibling, unrelated, and haploidentical-related donors
Montoro, J., Chorão, P., Bento, L., Cabrero, M., Martín, C., Novelli, S., Cadenas, I. G., Gutiérrez, G., López-Godino, O., Ferrá, C., et al
Bone marrow transplantation. 2020
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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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Alloreactivity: the Janus-face of hematopoietic stem cell transplantation
Gratwohl, A., Sureda, A., Cornelissen, J., Apperley, J., Dreger, P., Duarte, R., Greinix, H. T., Mc Grath, E., Kroeger, N., Lanza, F., et al
Leukemia. 2017;31(8):1752-1759
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Abstract
Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32838 such patients and compared it to 59692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.