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Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT
Salas, M. Q., Eikema, D. J., Koster, L., Maertens, J., Passweg, J., Finke, J., Broers, A. E. C., Koc, Y., Kröger, N., Ozkurt, Z. N., et al
Bone marrow transplantation. 2024
Abstract
We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.
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Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT
Paviglianiti, A., Labopin, M., Blaise, D., Socié, G., Bulabois, C. E., Lioure, B., Ceballos, P., Blau, I. W., Guillerm, G., Maertens, J., et al
Bone marrow transplantation. 2020
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Abstract
The association of Cyclosporine A (CsA) and mycophenolate mofetil (MMF) has increased in the setting of reduced intensity conditioning (RIC). Nevertheless, the use of CsA or CsA+MMF has not been reported in a large and uniform cohort. We analyzed 497 patients with acute myeloid leukemia in complete remission (CR) who underwent matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT). All patients received a fludarabine busulfan RIC regimen and anti-thymocyte globulin (ATG) with either CsA alone or in combination with MMF. The cumulative incidence (CI) of grade II-IV acute GvHD was 27% (95% CI 21-33%) for CsA and 33% (95% CI 27-38%) for CsA+MMF (p?=?0.25). The 2-year CI of chronic GvHD was 38% (95% CI 31-45%) and 33% (95% CI 28-39%) for the CsA and the CsA+MMF group, respectively (p?=?0.26). On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients. Our results support the importance of randomized trial to identify patients who could benefit from the addition of MMF in MUD HSCT.
PICO Summary
Population
Patients who underwent a 10/10 MUD HSCT for acute myeloid leukaemia (n=497)
Intervention
Cyclosporine A and mycophenolate mofetil (CsA + MMF, n=314)
Comparison
Cyclosporine A alone (CsA, n=183)
Outcome
The cumulative incidence (CI) of grade II-IV acute GvHD was 27% for CsA and 33% for CsA+MMF. The 2-year CI of chronic GvHD was 38% and 33% for the CsA and the CsA+MMF group, respectively. On multivariate analysis, no statistically significant differences with respect to relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS), acute and chronic GvHD were found between the two groups, also when conducting a subgroup analysis in peripheral blood stem cells (PBSC) recipients.
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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
Battipaglia, G., Labopin, M., Hamladji, R. M., Blaise, D., Chevallier, P., Brissot, E., Gerbitz, A., Socié, G., Afanasyev, B., Ciceri, F., et al
Cancer. 2020
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.
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ATIR101 administered after T-cell-depleted haploidentical HSCT reduces NRM and improves overall survival in acute leukemia
Roy, D. C., Walker, I., Maertens, J., Lewalle, P., Olavarria, E., Selleslag, D., Lachance, S., Buyse, M., Wang, K., Rovers, J., et al
Leukemia. 2020
Abstract
Overcoming graft-versus-host disease (GvHD) without increasing relapse and severe infections is a major challenge after allogeneic hematopoietic stem-cell transplantation (HSCT). ATIR101 is a haploidentical, naive cell-enriched T-cell product, depleted of recipient-alloreactive T cells to minimize the risk of GvHD and provide graft-versus-infection and -leukemia activity. Safety and efficacy of ATIR101 administered after T-cell-depleted haploidentical HSCT (TCD-haplo + ATIR101) without posttransplant immunosuppressors were evaluated in a Phase 2, multicenter study of 23 patients with acute leukemia and compared with an observational cohort undergoing TCD-haplo alone (n = 35), matched unrelated donor (MUD; n = 64), mismatched unrelated donor (MMUD; n = 37), and umbilical cord blood (UCB; n = 22) HSCT. The primary endpoint, 6-month non-relapse mortality (NRM), was 13% with TCD-haplo + ATIR101. One year post HSCT, TCD-haplo + ATIR101 resulted in lower NRM versus TCD-haplo alone (P = 0.008). GvHD-free, relapse-free survival (GRFS) was higher with TCD-haplo + ATIR101 versus MMUD and UCB (both P < 0.03; 1-year rates: 56.5%, 27.0%, and 22.7%, respectively) and was not statistically different from MUD (1 year: 40.6%). ATIR101 grafts with high third-party reactivity were associated with fewer clinically relevant viral infections. Results suggest that haploidentical, selective donor-cell depletion may eliminate requirements for posttransplant immunosuppressors without increasing GvHD risk, with similar GRFS to MUD. Following these results, a randomized Phase 3 trial versus posttransplant cyclophosphamide had been initiated.
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Impact of antithymocyte globulin on outcomes of allogeneic hematopoietic cell transplantation with TBI
Nagler, A., Labopin, M., Dholaria, B., Niittyvuopio, R., Maertens, J., Poire, X., Cornelissen, J., Remenyi, P., Bourhis, J. H., Beguin, Y., et al
Blood advances. 2019;3(13):1950-1960
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Abstract
The impact of the use of antithymocyte globulin (ATG) following a total body irradiation (TBI)-based myeloablative conditioning regimen has been poorly explored. We retrospectively analyzed 724 patients who underwent a first allogeneic hematopoietic cell transplantation (allo-HCT) following a TBI-based conditioning regimen for acute myeloid leukemia (AML) and compared the outcomes of 251 (35%) patients who received ATG (ATG group) with 473 (65%) patients who did not (non-ATG group). Median follow-up of surviving patients was 59 months (interquartile range, 28-83). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) for non-ATG and ATG groups in the first 100 days was 33% vs 24%, respectively (P = .0098). The 2-year cumulative incidence of chronic graft-versus-host disease (cGVHD) was reduced significantly in the ATG group in comparison with the non-ATG group (46% vs 34%, P = .003). Using multivariate analysis, in vivo T-cell depletion (ATG group) was independently associated with a decreased incidence of grade II-IV aGVHD (hazard ratio [HR], 0.28; P < .001), grade III-IV aGVHD (HR, 0.21; P < .001), cGVHD (HR, 0.63; P = .02), and nonrelapse mortality (NRM) (HR, 0.54; P = .02). Relapse risk, overall survival, and leukemia-free survival were similar between the 2 groups. Our results suggest that the addition of ATG to TBI-based myeloablative conditioning for allo-HCT in AML patients results in a significant reduction in aGVHD and cGVHD, translating into a significant reduction in NRM without increasing the relapse rate.
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Antilymphocyte Globulin for matched sibling donor transplantation in patients with myelofibrosis
Robin, M., Chevret, S., Koster, L., Wolschke, C., Yakoub-Agha, I., Bourhis, J. H., Chevallier, P., Cornelissen, J. J., Remenyi, P., Maertens, J., et al
Haematologica. 2019
Abstract
Antihuman T-lymphocyte immunoglobulin is still much debated in the setting of transplant from an HLA matched related donor. Acute and chronic graft-versus-host disease are the main cause of morbidity and mortality after allogeneic hematopoietic stem cell in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis. 287 patients were included in the study. Cumulative incidence of grade 2-4 acute graft-versus-host disease was 26% and 41% with or without antihuman T-lymphocyte immunoglobulin. Chronic graft-versus-host disease incidence was 52% and 55%. Non-adjusted overall Survival, Disease Free Survival and non-relapse mortality were 55% vs 53%, 49% vs 45%, and 32% vs 31%, respectively with or without antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that acute graft-versus-host disease risk was lower following antihuman T-lymphocyte immunoglobulin (Hazard ratio : 0.54, p=0.010) whilst it did not decrease the risk of chronic graft-versus-host disease. Hazard ratio for overall survival and non-relapse mortality were 0.66 and 0.64, with p-value at 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease and relapse free survival and relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases acute graft-versus-host disease risk without increasing relapse risk.
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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
Czerw, T., Labopin, M., Giebel, S., Socie, G., Volin, L., Fegueux, N., Masszi, T., Blaise, D., Chaganti, S., Cornelissen, J. J., et al
Cancer. 2018
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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. (c) 2018 American Cancer Society.