Older Age at Time of Allogeneic Stem Cell Transplant Is Associated with Inferior Outcomes in Patients with Acute Myeloid Leukemia
Authors: Avetian George , Ho Thuy , Murray Graeme F , Bouligny Ian M. , Maher Keri 
Published: December 2024

Background: Allogenic hematopoietic cell transplantation (alloSCT) is a potential curative consolidative therapy in many patients with acute myeloid leukemia (AML). Those with intermediate or high risk AML are suggested to have consultation with a transplant specialist to further assess candidacy. With the advent of more tolerable conditioning regimens, the upper age of commonly transplanted patients is ever increasing. Meanwhile, improved non-transplant therapies are also improving prognosis in these patients, which makes relative benefit of transplant in elderly AML less clear.

Methods: Retrospective analysis of 84 consecutive AML patients at Massey Comprehensive Cancer Center between 2014 and 2024 who underwent alloSCT for AML was conducted. Baseline characteristics including sex, Eastern Cooperation Oncology Group (ECOG) performance status scale, European LeukemiaNet (ELN) risk stratification, and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) scores were collected. Following propensity score matching for ELN adverse risk rates, patients were separated into two cohorts based on their age in years at time of alloSCT: 18-64 (n=58) and 65+ (n=26). Comparison of relapse-free survival (RFS) and overall survival from first day of alloSCT (OS) were calculated using the Kaplan-Meier method. Landmark analysis at 6 months, 12 months, and 24 months for mortality rates were conducted. Kruskal-Wallis test, Mann-Whitney U test, and chi-squared tests were used for statistical analyses.

Results: Following propensity score matching for ELN adverse risk rates (50.0% v. 50.0%, p=1.000), baseline characteristics including sex (48.3% v. 57.7% males, p=0.425), median ECOG score (1 v. 1, p=0.541), and median HCT-CI scores (3 v. 3.5, p=0.221) did not differ between the 18-64 and 65+ age cohorts, respectively. A difference was found between the younger and older age cohorts, respectively, with respect to median RFS (HR 1.977, p=0.017) and OS (HR 2.329, p=0.005). Median RFS was 921 days and 325 days for the 18-64 and 65+ age cohorts, respectively. Median OS for the 65+ age cohort was 410 days; median OS for younger cohort was not reached. Early mortality rates between the 18-64 and 65+ age cohorts were not different at 6 months (12.1% v. 19.2%, p=0.386), and became more pronounced at 12 months (25.9% v. 46.2%, p=0.066) and 24 months (31.0% v. 61.5%, p=0.008).

Conclusion: Our study demonstrates that age plays an important prognostic impact on success of alloSCT. While this is a well-known and expected phenomenon, it calls into question the strong push toward reduced-intensity or non-myeloablative transplant for functionally-fit elderly AML. This is particularly relevant with the changing treatment landscape in relapsed/refractory, targeted, and immunologic therapies for AML patients over the past several years. Specific clinical trials examining utility in transplant in such elderly AML patients to re-evaluate the utility of alloSCT in the modern era is warranted.