Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, health outcomes research
Methods: 142 patients undergoing allo-HCT for myeloid malignancies between February 2015 and December 2021 were included. Six patients underwent two subsequent allo-HCTs, four patients were excluded due to early (< 30 day) transplant related mortality, resulting in a total of 144 allo-HCTs. EMC was defined as < 95% donor cells at day 90-120 post allo-HCT. Fisher’s exact test was used to compare categorical variables. Univariate (UVA) and multivariate (MVA) Cox regression analyses were used to investigate factors associated with overall survival and relapse.
Results: Median age was 59 years (19-71), 41% were female and 9% were Hispanic or Latino. Majority of the patients underwent allo-HCT for acute myeloid leukemia (AML) (62%) or myelodysplastic syndrome (31%). Thirty-five percent of the patients with AML had adverse risk AML per ELN risk stratification. At time of transplant, bone marrow blast % were < 5% in 88% of patients of which 38% was MRD negative. Sixty-five percent of the patients had unrelated donors, 35% had a related donor [haplo-identical (54%) or matched sibling (46%)]. Median HCT-comorbidity index (CI) was 2 (range 0-9). Majority received peripheral blood stem cells (90%), reduced intensity conditioning (67%) and PTCY (72%) in combination with mycophenolate and tacrolimus (n=101) or sirolimus (n=2) for GVHD prophylaxis. Seventy-three percent was alive at last time of follow-up (median 2 years; range 0.15-7 years).
Comparing patients receiving PTCY vs no PTCY, no differences were seen in rates of acute-GVHD (p=0.26), relapse (p=0.82), or overall survival (p=0.84). A lower rate of chronic GVHD (cGVHD) (p=0.03) and a higher rate of EMC (p=0.04) were observed in patients that did receive PTCY. In UVA, MRD status (p=0.004), HCT-CI (p=0.005) and cGVHD (p=0.002) were associated with post-HCT OS, and remained independently prognostic in MVA (p=0.003,p=0.011, p=0.006, respectively). EMC (p=0.004) and AML adverse risk cytogenetics (p=0.018) were independently prognostic for relapse risk. Survival analysis restricted to adverse-risk AML patients found that EMC was associated with shorter relapse-free survival. Correlation analysis between mutational status and EMC or relapse status did not identify any mutation with a significant association, as did we not recognize any association with genomic classifications (e.g., DNA methylation or hydroxymethylation, chromatin-cohesin or splicing).
Conclusion: Our study highlights the feasibility of using PTCY in diverse donor settings. While PTCY was associated with a higher incidence of EMC and a lower rate of cGVHD, PTCY was not associated with a shorter overall survival or relapse risk, suggesting that the predictive value of EMC for relapse likely depends on the underlying disease. Further research is needed to re-evaluate the rol for PTCY in high-risk AML.
Figure 1. A. Overall survival analysis for all 144 patients stratified by PT-Cy. B. Relapse-free survival analysis for adverse-risk AML patients (n=29) stratified by EMC.
Disclosures: Patel: Agios: Membership on an entity's Board of Directors or advisory committees. Ramakrishnan Geethakumari: Kite: Consultancy; BMS: Consultancy; Rafael Pharma: Consultancy; Pharmacyclics LLC: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Cellectar Biosciences: Membership on an entity's Board of Directors or advisory committees. Madanat: Sierra Oncology, Stemline Therapeutics, Morphosys, Taiho, and Novartis: Membership on an entity's Board of Directors or advisory committees; BluePrint Medicines, GERON, OncLiv: Consultancy, Honoraria.
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