The Relationship between Age and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in a Cohort of Older Patients with Acute Myeloid Leukemia (AML)

Introduction: The use of allogeneic HSCT is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. However, there is evidence to suggest that older patients up to 80 years old may tolerate and benefit from intensive treatment, despite deteriorating organ function. This real-world analysis compared outcomes of Medicare-aged, chemotherapy-treated AML patients with or without HSCT.

Methods: We performed a retrospective cohort analysis of 4,772 patients with a first primary AML in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2013, were aged > 66 years, continuously enrolled in Medicare Part A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis, and had received chemotherapy treatment within 3 months of diagnosis. Demographic and clinical characteristics were compared between patients who received HSCT and those who did not, using chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival plots were used to assess overall survival. Cox proportional hazards regression modeling evaluated the independent effects of covariates on overall survival, including receipt of HSCT, age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region. Date of last follow-up was December 31, 2015, permitting a minimum 2-year follow-up.

Results: Of 4,772 patients with a first primary AML in the linked SEER-Medicare database, 403 (8%) underwent HSCT therapy after chemotherapy and 4,369 (92%) did not. Rates of HSCT increased over the study time period from 7% in 2000 to 12% in 2012 (P = 0.0033). Of the 403 patients who underwent HSCT, the majority (82%) were aged ≤ 75 years. Overall, patients in the HSCT group were younger at diagnosis (71 vs 75 years), more likely to be male (63% vs 54%), be married (66% vs 60%), less likely to have high-risk disease (11% vs 15% with prior MDS) or PPIs (4% vs 8%), and had lower comorbidity burden (59% vs 53% with a comorbidity score of 0) versus patients treated with chemotherapy only. In a subset analysis stratified by age, the relationships observed between patient characteristics and HSCT receipt persisted in the younger cohort of patients (≤ 75 years) but not in the older cohort (> 75 years). The unadjusted median overall survival was higher for the HSCT group (14.2 months) versus the non-HSCT group (4.8 months; log-rank P < 0.0001). In multivariate survival analysis, patients who underwent HSCT had a 40% lower risk of death versus those who did not undergo HSCT (hazard ratio [HR] 0.60; 95% CI 0.53-0.67). Advanced age, male sex, higher comorbidity score, prior MDS, and PPIs were significantly associated with higher risk of mortality. Stratifying by age, the survival benefit with HSCT was only demonstrated in the younger cohort aged ≤ 75 years (HR 0.53; 95% CI 0.46-0.60); no difference in mortality risk was noted in the older cohort aged > 75 years (HR 0.85; 95% CI 0.67-1.08).

Conclusions: Overall, only 8% of patients receiving antileukemic therapy underwent subsequent HSCT therapy, and 82% of patients who did undergo HSCT were aged ≤ 75 years. HSCT was associated with a 40% reduction in mortality risk versus patients receiving chemotherapy only, and the survival benefit was more pronounced among the younger cohort aged ≤ 75 years, with a 47% reduction in mortality risk. Chronologic age appears to be the driving factor in HSCT receipt and prognosis, and these findings provide important new information on real-world outcomes on the benefit of HSCT in an elderly population.