Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML)
Authors: Keegan Theresa H.M. , Muffly Lori S , Li Qian , Alvarez Elysia , Brunson Ann M , Malogolowkin Marcio , Wun Ted 
Published: October 2019

Abstract
Introduction: Adolescent and young adult (AYA) cancer survivors are at an increased risk of developing subsequent medical problems, including asthma/chronic obstructive pulmonary disorder, cardiovascular disease, diabetes and second cancers. However, few population-based studies have focused on these risks in AYAs with NHL, ALL or AML or considered whether the occurrence of these and other medical conditions differ by sociodemographic factors.
Methods: Data for patients aged 15-39 when diagnosed with NHL (n=4,459), ALL (n=1,100) and AML (n=1,107) during 1996-2012 and surviving a minimum of 2 years were obtained from the California Cancer Registry and followed in California hospital discharge databases. Discharge diagnoses were used to classify medical conditions as cardiac (hypertensive disease, ischemic heart disease, other heart disease), neurologic (stroke, seizure), endocrine (hypothyroidism, diabetes, ovarian/testicular dysfunction, other metabolic diseases), respiratory (asthma, chronic obstructive pulmonary disease), renal (chronic kidney disease, hemodialysis, kidney transplant), liver (chronic liver disease, pancreatitis, cirrhosis, liver transplant), and avascular necrosis. Second cancers were obtained from the cancer registry. We estimated the cumulative incidence (CMI) of developing each condition 10-years after diagnosis, accounting for death as a competing risk. We determined the impact of race/ethnicity, neighborhood socioeconomic status (SES), health insurance status and stem cell transplant (SCT) on the occurrence of each medical condition after adjusting for other demographic and clinical factors using multivariable Cox proportional hazards regression.
Results: The most common medical conditions among AYA survivors at 10-years were cardiac (CMI NHL: 11.6%; ALL= 20.5%; AML= 18.2%), endocrine (CMI NHL: 18.6%; ALL= 33.0%; AML= 25.9%) and respiratory (CMI NHL: 5.1%; ALL= 7.7%; AML= 6.8%) diseases. Avascular necrosis had the highest CMI in ALL patients (CMI NHL: 1.2%; ALL= 8.7%; AML= 2.5%). Neurologic (CMI NHL: 2.1%; ALL= 4.5%; AML= 4.9%) and liver (CMI NHL: 2.0%; ALL= 5.6%; AML= 4.4%) were more common in survivors of ALL and AML than NHL. Second cancers (2.3-2.5%) and renal diseases (2.2-3.5%) were less common at 10-years. NHL survivors with advanced stage disease had a higher incidence of all medical conditions, except second cancers. Chemotherapy was associated with a higher CMI of cardiac and endocrine conditions among NHL survivors; these associations could not be assessed in ALL and AML patients as nearly all patients received chemotherapy. Initial radiation therapy was not associated with a higher CMI of medical conditions in NHL or ALL survivors, but was associated with a higher CMI of respiratory, renal and endocrine diseases in AML survivors. In multivariable models, public or no insurance (vs private) was associated with a higher risk of most medical conditions in NHL and ALL survivors, but not AML survivors (Table). The risk of developing medical conditions varied by race/ethnicity, with Hispanics ALL survivors (vs non-Hispanic whites) at a higher risk of cardiac, renal, liver, endocrine, second cancers and neurologic diseases and black AML survivors at a higher risk of all medical conditions, except endocrine diseases. AYAs with NHL who resided in lower SES neighborhoods were at a higher risk for developing cardiac, respiratory and endocrine diseases; AML survivors in lower SES neighborhoods had a higher risk of respiratory diseases. Across all cancers, AYAs undergoing a SCT were at a higher risk of most medical conditions.
Conclusion: This study found that sociodemographic factors were associated with the risk of developing medical conditions in AYA NHL, ALL and AML survivors. As expected, the risk of medical conditions varied by cancer type and treatment, with those undergoing SCT having a higher risk of medical conditions regardless of cancer type. NHL and ALL survivors who were uninsured or publicly insured were at a consistently higher risk of developing medical conditions, as were Hispanic ALL survivors and Black AML survivors. Our findings highlight the higher burden of medical conditions in subgroups of cancer survivors that may relate to reduced access to preventive care, early detection/intervention and long-term surveillance.

Disclosures
Muffly: Shire Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding.