Self-Rated Health Is an Independent Predictor of Subsequent Late Mortality after Blood or Marrow Transplantation (BMT) Among Survivors of Lymphoid Malignancies: A BMTSS Report

Background: BMT is offered with curative intent to patients with lymphoid malignancies (acute lymphoblastic leukemia [ALL], and lymphoma). Despite the decline in early mortality due to refinement in transplantation strategies and advances in supportive care, BMT recipients carry a significant burden of late-occurring morbidity, placing them at high risk for late mortality when compared with the general population. Previous studies have identified several causes of late mortality including recurrence of primary cancer and treatment-related chronic health conditions (e.g., subsequent malignancies and cardiovascular disease). Self-rated health (SRH) is a single-item measure of an individual's evaluation of their health status and has been reported as an independent predictor of mortality in the general population and cancer patients treated with conventional therapy. The association between SRH and subsequent all-cause and cause-specific late mortality among BMT survivors of lymphoid malignancies has not been examined. Finally, sociodemographic and clinical factors associated with suboptimal SRH among BMT survivors remain unstudied.

Methods: We examined the prevalence of suboptimal SRH and its association with subsequent all-cause and cause-specific mortality after BMT among survivors of lymphoid malignancies. Study participants were drawn from BMTSS and included patients who were transplanted between 1974 and 2014 at three participating sites, with primary diagnosis of ALL, HL and NHL, and had survived ≥2y post-BMT. Participants (≥18y) completed a survey at a median of 9y from BMT and were followed for a median of 5y after survey completion for vital status and cause of death. Survivors provided information on sociodemographic characteristics, chronic health conditions (as diagnosed by their healthcare providers), health behaviors, and SRH (single item, rated as excellent, very good, good, fair or poor; excellent, very good or good SRH were classified as good SRH and all else as suboptimal SRH). National Death Index (NDI) Plus, Accurint database, and medical records provided vital status through December 2021. Multivariable regression analyses determined the association between SRH and all-cause mortality (Cox regression) and cause-specific mortality (recurrence-related [RRM] and non-recurrence related mortality [NRM]) (sub-distribution hazard regression) after adjusting for relevant sociodemographic, clinical variables and therapeutic exposures. Factors associated with suboptimal SRH were analyzed using multivariable logistic regression

Results: The cohort included 1,554 BMT survivors (ALL: n=318; lymphoma: 1,236); 33.0% allogeneic BMT; median age at BMT 45y; 59.1% males; 75.9% non-Hispanic white. Overall, 311 (20.0%) BMT survivors reported suboptimal SRH, and 319 patients died after survey completion (20.5%). BMT survivors who reported suboptimal SRH had a 1.7-fold greater hazard of all-cause mortality (95%CI=1.3-2.3), 1.9-fold increased risk of RRM (95%CI:1.0-3.4), and 1.5-fold increased risk of NRM (95%CI:1.0-2.3) compared to those who reported good SRH, after adjusting for age at survey, year of BMT (1974-1989; 1990-2004; 2005-2014), sex, race/ethnicity, socioeconomic status (SES), age at BMT, risk of relapse at BMT (standard; high), BMT type/cGvHD (autologous BMT; allogeneic BMT/no cGvHD; allogeneic BMT/cGvHD), conditioning intensity with or without total body irradiation, post-BMT relapse, grades 3-4 chronic health conditions, psychological distress, smoking, and alcohol consumption. Pain, low SES, psychological distress, lack of exercise, severe/life threating chronic health conditions, high risk of relapse at BMT, obesity and smoking were associated with suboptimal SRH.

Conclusions: This single-item measure could serve to identify vulnerable sub-populations that could benefit from interventions to mitigate the risk for subsequent mortality.

Forman:Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Lixte Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Armenian:Pfizer: Research Funding.