Malignancy in Patients with Sickle Cell Disease: A Single Center Observational Study
Authors: Thomas Theodore , Thomas Denise , French Kim , Blinder Morey A. 
Published: October 2019

Abstract
Introduction: Sickle cell disease (SCD) is an inherited disorder of red cells complicated by acute vaso-occlusion (VOC) and chronic organ damage in adults leading to a shortened lifespan. Improved management of SCD patients has resulted in increasing life expectancy so that the prevalence of malignancy in patients with SCD may be increasing. Patients with SCD often have comorbidities related to their disease that may limit their ability to receive cancer treatments and result in worse outcomes. Available literature describing cancer in SCD patients is limited to case reports and small retrospective reviews. This study describes a cohort of adult patients with SCD with a malignancy and the effect on their SCD.
Methods: The Adult Hemoglobinopathy Resource Center at Washington University has provided care for adult SCD patients throughout the St. Louis, Missouri metropolitan area since 1990. All patients have confirmed SCD (Hgb SS, Hgb SC, Hgb Sβ+, Hgb Sβ0, Hgb SC Harlem, Hgb S Other) and have been seen at least once since 2011 or are known to have died were included in this study. A retrospective chart review of these SCD patients was conducted and medical records were reviewed for malignancies. Demographic data and SCD history included: gender, SCD genotype, baseline Hgb, and hydroxyurea use. Cancer treatment history data included: age at and date of diagnosis, cancer screening, type and stage of malignancy, date and cause of death, complications of cancer treatments, and the number of hospitalizations/emergency departments visits for VOC in the year before and after cancer diagnosis. Categorical variables were analyzed using Fisher's exact test and continuous variable analyzed using student t-test. Patients were grouped into Hgb SS and non-Hgb SS for analysis to explore differences in outcomes. Overall survival (OS) was calculated based on date of diagnosis to date of death or censored at July 7, 2016. Commonly cited oncology literature was reviewed for the median OS for each malignancy based on stage. Each patient's actual survival was compared to the expected median OS for their respective malignancy. OS was classified as better or worse if actual survival time was at least equivalent to or shorter than cited median OS, respectively.
Results: From October 2011 to December 2015, 397 patients have been evaluated and 15 are known to have died. Of the surviving patients, the mean age is 35 yrs (range 18-76); 199 are female (52.1%), and 183 are male (47.9%). The hemoglobinopathies include SS-245, SC-106, Sβ+-24, Sβ0-5, SC Harlem-1, and unconfirmed-1. Overall, 85 patients have died since 1994. Eleven patients (Hgb SS-6, Hgb SC-3 and Hgb Sβ+-2) were found to have diagnoses of twelve malignancies. The diagnoses and number of patients include non-small cell lung-3, breast-2, and one each of germ cell tumor, Hodgkin lymphoma, colon, and papillary thyroid, extra-adrenal metastatic paraganglioma, tongue base squamous cell and prostate cancers. The incidence of malignancy in our cohort was 2.3% and the median age at cancer diagnosis was 41.8 yrs (range 19-68). Patients with Hgb SS trended towards having cancer diagnosed at a later age compared to non-Hgb SS patients (ages 52.3 vs 35.8 yrs respectively, p=0.1). Hgb SS patients had a lower baseline Hgb (p=0.00005) and higher frequency of hydroxyurea use (p=0.012) compared to non-Hgb SS patients at the time of cancer diagnosis. The median OS of patients was at least equivalent to expected OS in 2 out of 6 patients with Hgb SS and 4 out of 5 patients non-Hgb SS disease (p=0.16). Initial therapy consisted of surgery (5), radiation therapy (3, 1 curative and 2 palliative intent) and chemotherapy (4). Chemotherapy was indicated as standard of care but not administered to 4 patients secondary to comorbidities. There was no significant difference in VOC/year in the year before compared to the year after cancer diagnosis. Malignancy was identified by age appropriate cancer screening in 3 out of 4 applicable patients.
Conclusions: In adults with SCD, malignancy occurred in 2.3% of patients over about 25yrs. There was not an observed increase in pain crises requiring in-hospital or emergency department evaluations after cancer diagnosis. Patients with SCD should complete age appropriate cancer screening for early detection. There is a modest trend towards worse outcomes for patients with Hgb SS disease compared to the general population and compared to Hgb SC/Sβ+.

Disclosures
Blinder: CSL Behring: Honoraria; Novartis: Honoraria; Janssen: Honoraria.