Azacitidine (AZA) and Donor Lymphocyte Infusion (DLI) Is a Viable Salvage Approach for Chimerism-Only Relapse Following Haploidentical Donor Allogeneic Blood or Marrow Transplantation (BMT)

Post-BMT relapse of myeloid malignancies is fraught with limited options for salvage. AZA-DLI is commonly used, but the outcomes, especially in haploidentical donor post-transplant cyclophosphamide (PTCY) BMTs, are not well characterized. To describe the outcomes of AZA-DLI as a salvage strategy for post-BMT relapse in our uniformly managed institutional cohort to identify optimal timing and population for AZA-DLI. We conducted a retrospective chart review of all patients who underwent AZA-DLI for relapse after BMT at our center between January 2016 and November 2024. Patients received treatment for mixed chimerism only (≤95% donor chimerism) or for clinical relapse [increased blasts for acute myeloid leukemia (AML) or abnormal blood counts for myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN)]. Full donor chimerism (FDC) was defined as >95% donor chimerism in bone marrow or peripheral blood. Clinical improvement (CI) was evaluated in patients with clinical relapse and defined as a decrease in marrow and blood blasts in AML, or an improvement of blood counts in patients with MDS and MPN. Overall response rate (ORR) included patients achieving FDC or CI. Standard statistical methods were used to compare responses, and overall survival (OS) was calculated from the date of established post-BMT relapse. We identified 50 patients who met study criteria: 22 (44%) AML, 15 (30%) MDS, and 13 (26%) MPN. Thirty-seven (74%) patients underwent BMT using haploidentical donors. Other baseline details are shown in Figure 1. Time to relapse from BMT was ≤6 months in 11 (22%) patients, and >6 months in 39 (78%). Mixed chimerism and clinical relapse were noted in 14 (28%) and 36 (72%) patients, respectively. At 6 months from DLI, FDC was achieved in 9 (64.3%) patients with mixed chimerism versus 7 (19.4%) with clinical relapse (p = 0.0053). CI was noted in 4 (11.1%) patients with clinical relapse, resulting in an ORR of 64.3% in the mixed chimerism group and 30.6% in the clinical relapse group (p = 0.0519). OS at 1 year and 2 years was 85% (95% CI 54-96) and 60% (95% CI 29-81) in the mixed chimerism group and 72% (95% CI 55-84) and 34% (95% CI 19-50) in the clinical relapse group (p = 0.0383, Figure 2). When AZA-DLI was used for mixed chimerism, rates of grades II-IV acute graft-vs-host-disease (GVHD) were 35.7%, grades III-IV acute GVHD 21.4%, and chronic GVHD requiring systemic immunosuppression 21.4%. For clinical relapse, these rates were 16.7% ( p = 0.2521), 5.6% ( p = 0.1262), and 5.6% ( p = 0.1262 ) , respectively. Our data support AZA-DLI as a feasible strategy for managing post-BMT relapse, especially in a setting of mixed chimerism only. Close surveillance for GVHD is warranted.