In 2017, an estimated 1.3 million individuals were living with a hematologic malignancy (HM: leukemia, myeloma
or lymphoma) in the US. Frontline use of systemic high-intensity chemotherapy with or without radiation
characterizes the management of HM. Patients with progressive disease or at high risk of relapse are treated
with even higher intensity chemotherapy/radiation and blood or marrow transplantation (BMT); indeed, BMT is
often the only curative option for these patients. Steady improvements in outcome have resulted in a growing
number of BMT-HM survivors ? a population that is uniquely vulnerable to long-term chronic health conditions
(CHCs) that are directly related to the high-intensity therapeutic exposures (e.g., subsequent neoplasms, heart
failure). In 2000, we constructed a retrospective cohort of 2,333 BMT recipients (City of Hope [COH] or University
of Minnesota [UMN]; BMT: 1974-1998), who had survived ?2y (BMT Survivor Study [BMTSS]; R01 CA78938,
Bhatia). While BMTSS has successfully described the high burden of morbidity, accelerated aging and premature
mortality in BMT-HM patients, the modest sample size (n=2,333) and the older transplant era (1974-1998) has
limited the potential for new discoveries, especially in the face of evolving treatment strategies. We propose a
significant enhancement of the existing BMTSS cohort to now include 10,042 HM patients treated with BMT
between 1974 and 2014 at COH, UMN or UAB (BMT-HM), as well as a frequency-matched cohort of 3000 HM
patients treated with conventional therapy without BMT (non-BMT-HM). This enhanced infrastructure (BMTSS-
2) will be poised to determine the burden of morbidity borne by HM patients treated with or without BMT within
the context of individual HM diagnoses, and to understand the pathogenesis of treatment-related health
conditions in the setting of accelerated aging. The enhanced BMTSS-2 infrastructure will enable us to: i)
understand the long-term risk of health conditions experienced by HM patients treated with and without BMT; ii)
determine the association between treatment exposures and health conditions; iii) determine trends in health
conditions with changes in treatment strategies; iv) identify interactions between preventable modifiers
(comorbidities, health behaviors) and treatment exposures when determining risk of health conditions; v) study
the pathogenesis of treatment-related health conditions in the setting of accelerated aging, using genetic markers
for susceptibility and epigenetic markers for the association of the health conditions with aging; vi) use HIPAA-
compliant technology platform compatible with iOS/Android/iPad/Web-based applications to educate HM
patients and measure health behaviors in real time. This is the largest and most comprehensive attempt at
examining the health and wellbeing of HM patients treated with and without BMT. The overarching goal is to use
BMTSS-2 for translational research along two tracks: A) develop risk prediction models to identify HM recipients
at highest risk of treatment-related health conditions; and B) among those identified to be at highest risk, design
and test targeted interventions to prevent/ ameliorate these debilitating chronic health conditions.
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