Outcomes of Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based Gvhd Prophylaxis in Elderly Patients over 70 Years of Age with Acute Leukemia and Myelodysplastic Syndromes

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for acute leukemia (AL) and myelodysplastic syndromes (MDS). However, many AL/MDS patients are elderly, a demographic that presents unique challenges and complications following allo-HCT. Post-transplant cyclophosphamide (PT-Cy)-based graft versus host disease (GVHD) prophylaxis has shown improved outcomes in allo-HCT recipients and has been adapted as a new standard of care. Yet, the literature regarding outcomes of allo-HCT with PT-Cy-based GVHD prophylaxis in patients over 70 years is limited. Our study aimed to fill this gap by investigating the outcomes in elderly allo-HCT recipients aged over 70 who received PT-Cy-based GVHD prophylaxis.

Methods: A retrospective multicenter study was conducted, including first allo-HCT recipients with AL/MDS who received PT-Cy-based GVHD prophylaxis, in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 using P5737 data by Ustun et al. We examined the post-transplant outcomes, including overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute GVHD, chronic GVHD, and GvHD-free relapse-free survival (GRFS). Baseline factors were compared between groups using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox regression analyses were performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05.

Results: We included 865 patients with a median age of 57; 76 patients were older than 70, and 789 patients were aged 18-70 years. Of these, 59.5% were male (age >70: 63%). Ethnicity was Caucasians in 64% (age>70: 84%), African Americans and Hispanics in 28% (age>70: 12%), and others in 8% (age>70: 4%). Hematologic diagnoses were acute myeloid leukemia in 55% (age>70: 50%), MDS in 26% (age>70: 49%), and acute lymphoblastic leukemia in 20% (age>70: 1%). Donor types were matched siblings in 36% (age >70: 12%) or haplo in 64% (age>70: 88%). Reduced-intensity conditioning was performed in 57% of recipients (age>70: 92%). The graft source was peripheral blood stem cells in 65% of patients (age>70: 68%). The median graft cell dose was >5 million CD34 cells/kg in 40% of patients (age>70: 36%). All patients received PT-Cy-based GVHD prophylaxis. Karnofsky's performance status was ≥90% in 50% of patients (age>70: 42%), and 51% of the patients had an HCT-comorbidity index of <3 (age>70: 46%). The median follow-up time was 3.6 years (age>70: 3.5 years). In univariate analyses, OS (median years: 3.40 age 18-70 vs. 0.82 age >70, p<0.001), DFS (median years: 1.05 age 18-70 vs. 0.50 age >70, p<0.001), and GRFS (median years: 0.30 age 18-70 vs. 0.25 age >70, p=0.020) were significantly inferior in older patients over 70; however, in adjusted multivariate modes, age>70 years was not significantly associated with OS (HR 1.45, 95% CI 0.99-2.11, p=0.050), DFS (HR 1.29, 95% CI 0.9-1.84, p=0.165), or GRFS (HR 1.13, 95% CI 0.86-1.47, p=0.385). There were no significant differences between people aged> 70 and 18-70 regarding relapse (43% age 18-70 vs. 38% age>70, p=0.418), grade II-IV acute GVHD (36% age 18-70 vs. 34% age>70, p=0.757), chronic GVHD (34.5% age 18-70 vs. 28% age>70, p=0.057), and neutrophil engraftment (17 days in both groups). Age >70 years, compared to 18-70 years, was associated with a higher NRM (HR 2.81, 95% CI 1.92-4.13, p<0.001), and the relationship remained statistically significant in the adjusted multivariate model (HR 1.95, 95% CI 1.21-3.15, p=0.006). In the adjusted multivariate analyses, no significant association was observed for relapse, acute and chronic GVHD, and engraftment.

Conclusion: Our study found that patients over 70 years old with acute leukemia and MDS receiving allo-HCT with PT-Cy-based GVHD prophylaxis have a higher risk of non-relapse mortality. However, we did not observe significant differences in other outcomes, including overall and disease-free survival, relapse, acute and chronic GVHD, and GVHD-free relapse-free survival.