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Donor lymphocyte infusions after haploidentical stem cell transplantation with PTCY: A study on behalf of the EBMT cellular therapy & immunobiology working party
Santoro, N., Mooyaart, J. E., Devillier, R., Koc, Y., Vydra, J., Castagna, L., Gülbas, Z., Martin, J. D., Araujo, M. C., Kulagin, A., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Donor lymphocyte infusion (DLI) is a treatment option to prevent or treat relapse after allogeneic hematopoietic cell transplantation (HCT). We here report data for 173 patients who received one or multiple DLIs after haploidentical-HCT with post-transplant cyclophosphamide (PTCY) at 47 EBMT centers from 2009 to 2018. Indication for DLI was: prophylactic for 59(34.3%), preemptive for 20(11.6%), and therapeutic for 93(54.1%). For the prophylactic group, the median number of DLIs was 1 (IQR:1-2.5) with a median first dose of 0.1 × 10(6) CD3+ T cell/kg, for the preemptive 2 (IQR:1-3) with 0.5 × 10(6) CD3+ T cell/kg, for the therapeutic 1 (IQR:1-3) with 1 × 10(6)CD3+ Tcell/kg, respectively. OS after first DLI was 61% (46-75%) for prophylactic, 40% (19-61%) for preemptive, and 22% (13-31%) for therapeutic. CI of II-IV aGVHD and cGVHD was 17%(7-27%) and 53% (40-67%) for the prophylactic, 20% (2-38%) and 21% (3-39%) for the preemptive, 17% (9-24%) and 24% (15-33%) for the therapeutic group, respectively. Our data show great variability in the indications and modalities of DLI across responding EBMT centers. Survival rates remain relatively low in patients with active disease. While the cumulative incidence of aGVHD appears acceptable, we showed a high incidence proportion of cGVHD in the prophylactic group, compared with preemptive and therapeutic DLI. These data should be investigated further in prospective clinical trials.
PICO Summary
Population
Adults drawn from 47 EBMT centres receiving donor lymphocyte infusions (DLIs) after haploidentical transplant with post-transplant cyclophosphamide (n=173)
Intervention
DLIs for a prophylactic indication (n=59)
Comparison
DLIs for a pre-emptive indication (n=20), or a therapeutic indication (n=93)
Outcome
For the prophylactic group, the median number of DLIs was 1 (IQR:1-2.5) with a median first dose of 0.1 × 10(6) CD3+ T cell/kg, for the pre-emptive 2 (IQR:1-3) with 0.5 × 10(6) CD3+ T cell/kg, for the therapeutic 1 (IQR:1-3) with 1 × 10(6)CD3+ Tcell/kg, respectively. Overall survival after first DLI was 61% (46-75%) for prophylactic, 40% (19-61%) for pre-emptive, and 22% (13-31%) for therapeutic. Cumulative incidence of II-IV acute GVHD and chronic GVHD was 17%(7-27%) and 53% (40-67%) for the prophylactic, 20% (2-38%) and 21% (3-39%) for the pre-emptive, 17% (9-24%) and 24% (15-33%) for the therapeutic group, respectively.
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The Role of Donor Lymphocyte Infusion (DLI) in Post Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era
Schmidt, S., Liu, Y., Hu, Z. H., Williams, K. M., Lazarus, H. M., Vij, R., Kharfan-Dabaja, M. A., Orti, G., Wiernik, P. H., Weisdorf, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKI) with or without donor lymphocyte infusions (DLI), however the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002-2014 who underwent HCT for CML and were alive 30 days post relapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups 1) TKI alone n=128, 2) TKI with DLI n=48, and 3) DLI without TKI n=39. In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients that received a DLI alone compared to a TKI with DLI had inferior survival HR 2.28 (95% CI 1.23-4.24; p=0.009). Those who received TKI alone had similar survival compared to those who received TKI with DLI (p=0.81). These data supports that despite use of TKI pre-transplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data does not suggest that adding a DLI to TKI adds an improvement in OS.
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Association of Second Allogeneic Hematopoietic Cell Transplant vs Donor Lymphocyte Infusion With Overall Survival in Patients With Acute Myeloid Leukemia Relapse
Kharfan-Dabaja, M. A., Labopin, M., Polge, E., Nishihori, T., Bazarbachi, A., Finke, J., Stadler, M., Ehninger, G., Lioure, B., Schaap, N., et al
JAMA oncology. 2018
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Abstract
Importance: The optimal treatment approach to patients with acute myeloid leukemia (AML) who relapse after an allogeneic hematopoietic cell transplant (allo-HCT) remains elusive. No randomized clinical trial comparing survival outcomes of a second allo-HCT (allo-HCT2) vs donor lymphocyte infusion (DLI) has been conducted to date. Objective: To compare overall survival (OS) after an allo-HCT2 or DLI in relapsed AML after a first allo-HCT. Design, Setting, and Participants: A retrospective registry study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation involving 418 adults who received an allo-HCT2 (n = 137) or DLI (n = 281) for postallograft-relapsed AML. Analysis was assessed on the principle of intent-to-first received intervention. The data were collected from November 21, 2015, to May 15, 2017, and analysis was performed June 1, 2017. Main Outcomes and Measures: Number of patients with relapsed AML who are alive after 2 years and 5 years from receiving an allo-HCT2 or DLI. Results: Of the 418 patients, 228 (54.5%) were men; mean age was 46.2 years (interquartile range, 36.5-56.9 years). There was no apparent difference in OS whether an allo-HCT2 or DLI was prescribed (2-year OS with allo-HCT2, 26%; 5-year OS with allo-HCT2, 19%; 2-year OS with DLI, 25%; 5-year OS with DLI, 15%; P = .86). Overall survival was better if either of these procedures was offered when the patient was in complete remission (hazard ratio, 0.55; 95% CI, 0.41-0.74; P < .001). Conversely, OS was low for patients relapsing within less than 6 months after an allo-HCT1, regardless of the treatment prescribed (5-year OS: allo-HCT2, 9%; 95% CI, 1%-17% vs DLI, 4%; 95% CI, 1%-8%; P = .86). Conclusion and Relevance: Heterogeneity of the patient-, disease-, and treatment-related characteristics limit the ability to recommend one approach over another. Findings of this study highlight that best outcomes seem to be achieved in patients relapsing 6 or more months from an allo-HCT1 or those in complete remission at the time of either allo-HCT2 or DLI.
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Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia - a matched pair analysis by the Acute Leukaemia Working Party of EBMT
Schmid, C., Labopin, M., Schaap, N., Veelken, H., Schleuning, M., Stadler, M., Finke, J., Hurst, E., Baron, F., Ringden, O., et al
British journal of haematology. 2018
Abstract
Strategies for relapse prevention after allogeneic transplantation in acute leukaemia are warranted. A registry-based matched-pair analysis evaluated the efficacy of prophylactic donor lymphocyte infusion (proDLI). Adults receiving proDLI in complete remission (CR) and controls were pair-matched for age, diagnosis, cytogenetics, stage, donor, gender, conditioning and T-cell depletion. Eighty-nine pairs were identified (median follow-up: 6.9 years). Within the entire cohort, no difference was observed. However, among patients with high-risk acute myeloid leukaemia (AML) (unfavourable cytogenetics and/or transplanted beyond first CR), proDLI recipients had improved overall survival (69.8% vs. 40.2% in controls, P = 0.027). ProDLI has moderate efficacy, but can contribute to improved outcome in high-risk AML.