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Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT
Battipaglia, G., Galimard, J. E., Labopin, M., Raiola, A. M., Blaise, D., Ruggeri, A., Koc, Y., Gülbas, Z., Vitek, A., Sica, S., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.
PICO Summary
Population
Adults with acute myeloid leukaemia, undergoing allo-HCT with post-transplant cyclophosphamide in first or second complete remission, identified from the EBMT database (n=1751)
Intervention
Haploidentical transplantation: Haplo using bone marrow (Haplo-BM, n = 647) or using peripheral blood (Haplo-PB, n = 949))
Comparison
One-antigen mismatched unrelated donor transplantation (1Ag-MMUD-PB, n = 155)
Outcome
Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24; HR 2.65, 95% CI 1.46-4.81, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14; Haplo-PB: 1.47, 95% CI 1.05-2.05); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21; Haplo-PB: HR 1.51, 95% CI 1.05-2.19). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD.
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Outcomes of Unmanipulated Haploidentical Transplantation Using Post-Transplant Cyclophosphamide (PT-Cy) in Pediatric Patients With Acute Lymphoblastic Leukemia
Ruggeri, A., Galimard, J. E., Paina, O., Fagioli, F., Tbakhi, A., Yesilipek, A., Navarro, J. M. F., Faraci, M., Hamladji, R. M., Skorobogatova, E., et al
Transplantation and cellular therapy. 2021;27(5):424.e1-424.e9
Abstract
HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.
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Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT
Sanz, J., Galimard, J. E., Labopin, M., Afanasyev, B., Sergeevich, M. I., Angelucci, E., Kröger, N., Koc, Y., Ciceri, F., Diez-Martin, J. L., et al
Journal of hematology & oncology. 2021;14(1):84
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Free full text
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Editor's Choice
Abstract
BACKGROUND There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). METHODS We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n?=?78), matched unrelated (MUD) (n?=?94) and haploidentical family (Haplo) (n?=?297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. RESULTS Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p?=?0.4); 13%, 15%, and 15% (p?=?0.8); 35%, 50%, and 42% (p?=?0.01); and 11%, 17%, and 21% (p?=?0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p?=?0.8); and 21%, 18%, and 21% (p?=?0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p?=?0.8); 66%, 69%, and 62% (p?=?0.8); and 46%, 44%, and 35% (p?=?0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. CONCLUSIONS Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia (ALL) receiving allogeneic transplant in CR1 with prophylaxis with post-transplant cyclophosphamide (PTCy) prophylaxis (n=469)
Intervention
Haploidentical transplantation (n=297)
Comparison
Matched unrelated donor (MUD, n=94); matched sibling donor (MSD, n=78)
Outcome
Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34%; 13%, 15%, and 15%; 35%, 50%, and 42%; and 11%, 17%, and 21%, respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% and 21%, 18%, and 21% for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51%; 66%, 69%, and 62%; and 46%, 44%, and 35%, respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better leukaemia free survival.
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Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT
Sanz, J., Galimard, J. E., Labopin, M., Afanasyev, B., Angelucci, E., Ciceri, F., Blaise, D., Cornelissen, J. J., Meijer, E., Diez-Martin, J. L., et al
Journal of hematology & oncology. 2020;13(1):46
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.
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Allogeneic peripheral blood stem cell transplantation with anti-thymocyte globulin versus allogeneic bone marrow transplantation without anti-thymocyte globulin
Baron, F., Galimard, J. E., Labopin, M., Yakoub-Agha, I., Niittyvuopio, R., Kroger, N., Griskevicius, L., Wu, D., Forcade, E., Richard, C., et al
Haematologica. 2019
Abstract
We compared severe graft-versus-host-disease free and relapse-free survival and other transplantation outcomes of acute myeloid leukemia patients given bone marrow without anti-thymocyte globulin, versus peripheral blood stem cells with anti-thymocyte globulin after myeloablative conditioning. In the cohort of patients receiving grafts from a human-leukocyte-antigen matched sibling donor, patients given peripheral blood stem cells with anti-thymocyte globulin (n=1,021) and those given bone marrow without anti-thymocyte globulin (n=1,633) presented comparable severe graft-versus-host-disease free and relapse-free (HR=0.9, 95% CI: 0.8-1.1, P=0.5) and overall (HR=1.0, 95% CI: 0.8-1.2, P=0.8) survival. They had however, a lower incidence of chronic graft-versus-host disease (HR=0.7, 95% CI: 0.6-0.9; P=0.01). In the cohort of patients receiving grafts from human-leukocyte-antigen matched unrelated donor, patients given peripheral blood stem cells with anti-thymocyte globulin (n=2,318) had better severe graft-versus-host-disease free and relapse-free survival than those given bone marrow without anti-thymocyte globulin (n=303) (HR=0.8, 95% CI: 0.6-0.9, P=0.001). They also had a lower incidence of chronic graft-versus-host disease (HR=0.6, 95% CI: 0.5-0.8, P=0.0006) and better overall survival (HR=0.8, 95% CI: 0.6-1.0, P=0.04). In summary, these data suggest that peripheral blood stem cells with anti-thymocyte globulin results in comparable (in the case of sibling donor) or significantly better (in the case of unrelated donor) severe graft-versus-host-disease free and relapse-free survival than bone marrow without anti-thymocyte globulin in patients with acute myeloid leukemia in complete remission receiving grafts after myeloablative conditioning.