Burden of Long-Term Morbidity Borne by Survivors of Acute Myeloid Leukemia (AML) Treated with Blood or Marrow Transplantation (BMT) – Results of the BMT Survivor Study (BMTSS)

Background: Blood or marrow transplantation (BMT) is an integral part of consolidation and/or salvage therapy for patients with acute myeloid leukemia (AML). With the growing population of AML survivors, there is a need to understand the quality of their survival. Methods: This multi-site study included 1,369 2y survivors who underwent BMT for AML between 1974 and 2014 at age ≥21y and 1,310 siblings. Using Common Terminology Criteria for Adverse Events, severe/life-threatening and fatal chronic health conditions were identified. Multivariable regression analysis was used to compare the risk of severe/life-threatening conditions and health status between survivors and siblings, and to identify risk factors for grades 3-5 chronic health conditions among BMT survivors. Findings: The cumulative incidence of severe/life-threatening conditions by age 70 was 74.7% in BMT survivors compared to 48.7% in siblings (p<0.001), yielding 3.8-fold higher odds of severe/life-threatening conditions (95%CI=3.1-4.6) among the BMT survivors. The most prevalent conditions included subsequent neoplasms, diabetes, cataracts, venous thromboembolism, and joint replacement. Survivors were more likely to report poor general health (OR=3.8, 95%CI=2.8-5.1), activity limitation (OR=3.7, 95%CI=3.0-4.5), and functional impairment (OR=2.9, 95%CI=2.3-3.6). Among BMT recipients, the 20y cumulative incidence of severe/life-threatening/fatal conditions was 68%. History of chronic graft versus host disease was associated with a higher risk of pulmonary disease (HR=3.1, 95%CI=1.0-9.3), cataract (HR=2.6, 95%CI=1.3-3.8), and venous thromboembolism (HR=2.3, 95%CI=1.2-4.6). Relapse-related mortality plateaued at 30%, while non-relapse-related mortality continued to increase, approaching 50% at 30 years. Interpretation: The burden of severe/life-threatening conditions is substantially higher in BMT recipients when compared with an unaffected comparison group, informing the need for close monitoring to anticipate and manage morbidity. Funding: This study was supported in part by grants from the National Cancer Institute (R01 CA078938, U01 CA213140), and the Leukemia Lymphoma Society (R6502-16) Declaration of Interest: None to declare. Ethical Approval: UAB serves as the single Institutional Review Board of record; participants provided informed consent