Azacitidine and donor lymphocyte infusion for patients with relapsed acute myeloid leukemia and myelodysplastic syndromes after allogeneic hematopoietic stem cell transplantation: A meta-analysis

Abstract

BackgroundFor patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), azacitidine with donor lymphocyte infusion (DLI) is a feasible option to perform a preemptive or salvage treatment. However, its efficacy lacked comprehensive analysis, and this study aimed to fill this gap.MethodsWe searched potential studies in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials. Thirteen studies involving 811 patients were analyzed. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI). Subgroup analysis was performed to explore the source of heterogeneity.ResultsThe rate of pooled complete remission + partial remission (CR + PR), CR, and 2-year overall survival (OS) were 30% (95% CI: 22%–39%), 21% (95% CI: 16%–28%), and 31% (95% CI: 27%–35%), respectively. The pooled acute graft-versus-host disease (GvHD) and chronic GvHD rates were 15% (95% CI: 9%–23%) and 14% (95% CI: 8%–23%), respectively. Adverse cytogenetics and a higher percentage of bone marrow (BM) blasts at relapse were correlated with worse CR + PR and CR (interaction p < 0.05). Higher 2-year OS was found in patients with lower BM blasts at relapse or a longer time from allo-HSCT to relapse (interaction p < 0.05). Furthermore, the preemptive treatment for molecular relapse/minimal residual disease positivity resulted in much better outcomes than that for hematological relapse, both in terms of CR and 2-year OS (interaction p < 0.001).ConclusionThe regimen of azacitidine and DLI could safely improve the outcomes of relapsed AML/MDS after allo-HSCT, especially in those with signs of early relapse. The administration of targeted medicines in azacitidine-based therapies may further improve the outcomes of relapsed AML/MDS.

Prophylactic donor lymphocyte infusion after haploidentical hematopoietic cell transplantation and post‐transplant cyclophosphamide for treatment of high‐risk myeloid neoplasms in children: A retrospective study

“…The to be only 11%−30%. 20,21 Studies have shown that the application of pro-DLI in the haploidentical setting could help 49.1%−67.8% of the patients with MNs experience long-term survival and decrease the relapse to 14.7%−32.4%. [22][23][24] While, there is limited experience with use of pro-DLI in pediatric MN patients.…”

“…GVL effects make DLI currently one of the most common interventions used for post‐transplant relapse of hematological malignancies. However, unlike chronic myeloid leukemia, MNs recurring after allo‐HSCT do not respond well to DLI, with OS rates reported to be only 11%−30% 20,21 . Studies have shown that the application of pro‐DLI in the haploidentical setting could help 49.1%−67.8% of the patients with MNs experience long‐term survival and decrease the relapse to 14.7%−32.4% 22 – 24 .…”

Editorial: The latest advances in transplantation for AML

“…In this setting, the association between DLI, Azacitidine (AZA), and Venetoclax in 26 AML patients who relapsed after transplant has been recently published with an overall response rate of 61.5% (voce 98 di Bonifazi diventa (6). (7) focused their attention on the use of AZA and DLI in their meta-analysis. Searching in PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials, they found and analyzed 13 studies involving 811 patients.…”

“…( 7 ) focused their attention on the use of AZA and DLI in their meta-analysis. Searching in PUBMED, EMBASE, and Cochrane Central Register of Controlled Trials, they found and analyzed 13 studies involving 811 patients.…”

“…Molecular stratification has become fundamental not only for risk stratification but also for the identification of druggable mutations that could be used not only in the phase preceding transplant in order to reduce minimal residual disease but also in the post-transplant period as a further consolidation of the remission obtained. From the review of ( 5 ) and the meta-analysis from ( 7 ), we can assume that there is a need to find effective regimens after transplant that are able to combine the donor T-cell immunological effect with target therapies or novel molecules, and for this specific aim, we need to deepen the biological insights underlying post-transplant relapse.…”