Background: We recently reported a unique pattern of cancer incidence among sickle cell disease (SCD) patients compared to the general population, with SCD patients having a higher incidence of hematologic malignancies and lower incidence of solid tumors. As few studies have focused on cancer in SCD patients, we sought to identify risk factors for the development of cancer among SCD patients and assess cancer survival among those with SCD compared to a matched cohort of cancer patients without SCD.

Methods: SCD patients were previously identified in California (1991-2014) using hospitalization and emergency department databases and linked to the California Cancer Registry to identify patients with cancer. Conditional multivariable logistic regression was used to identify risk factors for cancer development overall, and for hematologic and solid tumors separately. In these analyses, we matched each SCD cancer patient to 4 SCD patients without cancer on race/ethnicity, gender, age of SCD identification in the databases and follow-up time. Risk factors were evaluated prior to age at cancer diagnosis or matched age and included number of transfusions, SCD severity (severe SCD was defined as averaging ≥3 visits per year over the study period), and specific Elixhauser comorbidities (fluid and electrolyte disorders, deficiency anemias, coagulopathy, obesity, liver disease, renal disease, chronic pulmonary disease, rheumatoid arthritis/collagen vascular diseases, and HIV/AIDS). Univariate predictors with p<0.2 were included in the multivariable model. To determine the impact of SCD on overall and cancer-specific survival after a cancer diagnosis, conditional multivariable Cox proportional hazards regression was used, with each SCD cancer patient matched to 4 non-SCD cancer patients on age, year of diagnosis, gender, race/ethnicity, cancer site and histology. Survival models were stratified by chemotherapy and stage and adjusted for radiation treatment, neighborhood socioeconomic status, and health insurance at diagnosis/initial treatment. Results are presented as odds ratios (OR), hazard ratios (HR) and 95% confidence intervals (CI).

Results: Among 6423 patients with SCD, 115 were diagnosed with a first primary cancer, with a median age of diagnosis of 46 years. In the matched analysis examining risk factors for cancer development, we included 552 SCD patients (n=112 with cancer; n=31 hematologic/n=81 solid, n=440 without cancer). Overall, deficiency anemias, coagulopathy, and liver disease were associated with an increased likelihood of cancer. In analyses by cancer type, we found that coagulopathy was associated with a 3-fold increased likelihood of developing a hematologic cancer (OR=3.09, 95% CI=1.11-8.61), and number of prior transfusions did not significantly increase the risk for hematologic cancers (Table). Deficiency anemias and coagulopathy was associated with a 2-3 fold increased likelihood of solid tumor development, but no association was observed with number of prior transfusions. In the matched analysis examining survival, we included 461 cancer patients (n=100 with SCD; n=361 without SCD). In multivariable models, SCD was associated with a 40% increased risk of all-cause mortality compared to similarly matched cancer patients without SCD; specifically, severe SCD patients were at 78% increased mortality (HR=1.78, 95% CI= 1.15-2.74), while less severe SCD patients were no different than non-SCD cancer patients (HR=1.12, 95% CI= 0.71-1.75) (Figure). However, cancer-specific mortality was not increased by SCD (HR=0.79, 95% CI=0.49-1.26).

Conclusions: Deficiency anemias and coagulopathy, but not number of prior transfusions, were associated with an increased likelihood of developing cancer. In addition, SCD patients with severe disease had worse survival than a matched non-SCD cancer cohort. However, cancer-specific survival was not affected by SCD. These results suggest that cancer outcomes in patients with SCD may not differ from those without SCD, and SCD cancer patients should be treated with curative intent.


Wun: Janssen: Other: Steering Committee for Cassini Study and Callisto Program, Research Funding; Pfizer: Other: Steering Committee: RESET study, Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.

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