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On behalf of the SFGM-TC: prophylactic donor lymphocyte infusion in patients treated with allogeneic stem-cell transplantation for high-risk myelodysplastic syndrome and acute myeloid leukemia
Guisnel, C., Schirmer, L., Morisset, S., Robin, M., Labussière-Wallet, H., Duléry, R., Ceballos, P., Forcade, E., Nguyen, S., Poiré, X., et al
Acta haematologica. 2023
Abstract
INTRODUCTION Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, it is still associated with a significant risk of relapse due to mechanisms of escape from the control of alloreactive T cells. Repetitive adjuvant donor lymphocyte infusions (DLI), termed prophylactic DLI (proDLI), as an effective strategy in preventing relapse is still debated. METHODS We performed a retrospective multicenter study to evaluate the efficacy of proDLI in allografted AML and MDS. We identified 56 patients treated with proDLI (DLI planned in full chimeras without any sign of disease relapse) and matched them to 167 patients in control group, (DLI performed for mixed chimerism or positive minimal residual disease) based on similar age, initial disease, cytogenetic prognosis, and conditioning intensity. RESULTS In univariate analysis, the incidence of severe aGVHD at 100 days and incidence of all grades of chronic GVHD 1 year after allo-HSCT were similar in the two groups. We also observed a trend of higher 3-year RI (52.61% [95% confidence interval 25.99-79.23]) in the proDLI group versus the control group (29.31% [20.28-38.34], p=0.067). However, 3-year overall survival (p=0.892), progression-free survival (p=0.239), and non-relapse mortality (p=0.343) were similar between the two groups. In multivariate analysis, the only factor influencing overall and progression-free survival was anti-thymocyte globulin administration during the conditioning regimen. DISCUSSION/CONCLUSION The proDLI strategy had an acceptable toxicity profile but did not improve patient outcomes compared to the pre-emptive strategy.
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Prophylactic or preemptive low-dose azacitidine and donor lymphocyte infusion to prevent disease relapse following allogeneic transplantation in patients with high risk acute myeloid leukemia or myelodysplastic syndrome
Guillaume, T., Thépot, S., Peterlin, P., Ceballos, P., Bourgeois, A. L., Garnier, A., Orvain, C., Giltat, A., François, S., Bris, Y. L., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Because of the persistently high rates of relapse of patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) following allogeneic stem cell transplantation, maintenance post-transplant therapy has been proposed. We previously initiated a Phase II trial in which epigenetic therapy was combined with immunotherapy in an attempt to reduce disease relapse. In that study, low dose azacitidine (AZA) and escalating dose of donor lymphocyte infusion (DLI) were given as maintenance treatment. In the present study, we retrospectively analyze a larger cohort of patients receiving post-transplantation maintenance therapy plus an update of some patients of the earlier study. OBJECTIVES To analyze the cumulative incidence of relapse (CIR), overall survival (OS), progression-free survival (PFS), incidence of acute and chronic graft-versus-host disease (GVHD) of patients with high-risk AML or MDS receiving a post-transplant maintenance treatment with AZA with or without DLI. STUDY DESIGN We retrospectively analyzed 77 patients (54 AML, 23 MDS) considered to be at high-risk based on either their genomic or clinical status at transplant. Following allogeneic transplantation, they received at least one cycle of prophylactic or preemptive low-dose AZA with or without escalating doses of DLI to prevent disease relapse. RESULTS Almost half of the patients (47%) were able to receive the full 12 cycles of scheduled AZA and a majority of patients (79%) received at least one DLI. With a median follow-up of 24 months, 19 patients (25%, 16 AML, 3 MDS) relapsed with a median time of 9.8 months (range 4-58.6 months), giving a 22% CIR at 24 months. OS and PFS at 24 months were 70.8% and 68.3% respectively. The cumulative incidence of acute GvHD Grade II-IV and chronic GvHD was 27.4% and 45%, respectively. Only a minority of patients (11%) requiring delayed administration of AZA. CONCLUSIONS These findings confirm that AZA-DLI maintenance is both tolerable and effective in reducing post-transplantation relapse risk.
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Prospective phase II study of prophylactic low-dose azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high-risk acute myeloid leukemia and myelodysplastic syndrome
Guillaume, T., Malard, F., Magro, L., Labopin, M., Tabrizi, R., Borel, C., Chevallier, P., Vigouroux, S., Peterlin, P., Garnier, A., et al
Bone marrow transplantation. 2019
Abstract
Thirty patients, with high-risk acute myeloid leukemia (AML, n = 20) or myelodysplastic syndrome (MDS, n = 10), were enrolled in a phase II trial entailing prophylactic post-transplant azacitidine (AZA) plus escalated doses of donor lymphocyte infusion (DLI). The median number of AZA cycles was 5 (1-12) with 10 patients (33%) completing the 12 projected cycles. DLI were performed in 17 patients: 5 received one DLI, 2 received 2 DLI and 8 received 3 infusions. AZA was well tolerated, but discontinued in 20 patients primarily due to graft-versus-host disease (GvHD) and relapse. The cumulative incidence (CI) of grade 1-3 acute GvHD was 31.5% and the chronic GvHD CI was 53% at 2 years. At a median follow-up of 49 months (27-63), 18 patients are alive. The overall and disease-free survivals are 65.5% (CI 95% = 48.2-82.8) at 2 years. Cause of death was mainly relapse for 9 patients. The median time to relapse was 7 months (2.5-58) and the cumulative incidence of relapse at 2 years was 27.6% (CI 95% = 12.8-44.6). These results confirm that AZA is well tolerated as a prophylactic treatment to reduce the risk of post-transplantation relapse and compared favorably to those of patients who receive no post-transplant maintenance.
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Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)
Mamez, A. C., Levy, V., Chevallier, P., Blaise, D., Vigouroux, S., Xhaard, A., Fegueux, N., Contentin, N., Beguin, Y., Ifrah, N., et al
Bone Marrow Transplantation. 2016;51(3):358-64
Abstract
Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68-48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04-16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17-0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease.