Co-Diagnosis of Sickle Cell and Chronic Myelogenous Leukemia: Exploratory Analysis from a Nationally Representative Database

Background: Chronic myelogenous leukemia (CML) developing in patients with sickle cell disease (SCD) has been reported infrequently in case studies to date (1). Prevalent thought relates its infrequency to the shortened life expectancy in the SCD population. However, with advancements in medical care, longevity of these patients has been increasing. Resultingly, risk factors for CML related to their disease and its treatments may accumulate, including chronic inflammation, heightened cell turnover, iron overload, immunomodulation from frequent transfusions, blood and marrow transplantation, and hydroxyurea use (2,3). Most specifically, the elevated and continuous inflammatory cell stimulation due to vaso-occlusion may enhance changes in granulocytic cell differentiation, increasing the risk for CML (3). By leveraging a nationwide database, we aim to describe characteristics associated with the development of CML in SCD patients.

Methods: Hospitalizations for SCD and CML were identified using ICD-10 coding from the 2020 National Inpatient Sample (NIS). Those hospitalizations with a co-diagnosis of SCD and CML were included in this study, and further evaluated for demographics, comorbidities, transfusion status, length of stay, mortality, and charges during admission.

The NIS is the largest all-payer inpatient database in the US and approximates a 20% stratified sample of inpatient discharges from >5000 hospitals across 48 states (98% of U.S. population). Sampling weights were applied to generate nationally representative estimates.

Results: In the 2020 NIS sample upon weighting, there were 60 hospitalizations with a co-diagnosis of SCD and CML. The vast majority of these patients presented with active CML (92%) and in sickle cell crisis (83%). Overall, half of the sample comprised those patients who were between the ages of 29.5-49 years old, with a median age of 40.5. Fifty percent (n=30) of the hospitalizations were female; 92% (n=55) were African American; 58% were hospitalized in the Southern region; 25% in the West, and 17% in the Northeastern United States. The majority of hospitalizations (92%) occurred in teaching hospitals and 83% were in large-bed size hospitals.

Common comorbidities were similar to that expected in the general SCD population, including history of transient ischemic attack (42%), history of pulmonary embolism/venous thromboembolism (42%), chronic kidney disease (33%), anemia (33%), and pulmonary hypertension (33%). Seventeen percent of patients had a transfusion during the hospitalization (n=15). The mean length of stay among these hospitalizations was 4.25 days. There were no deaths during these hospitalizations. Mean charges during hospitalization were $53,973.

Conclusion: Previously observed in rare case studies, here we present an exploratory analysis from a national inpatient database demonstrating a population of 60 adult patients with SCD and a co-diagnosis of CML. Specifically, we observe concomitant development of CML in the SCD patient population correlated with a younger age (median age 40.5) than expected compared to traditional CML patients (median age 64). There is some evidence to suggest that chronic inflammation associated with sickle cell with extended life expectancies and treatment burden may be associated with myeloid cancers. These studies will need to be followed up with prospective analyses to investigate a potential increased risk of CML in the SCD population.

Literature Cited:

1. Chen L et al., Chronic myelogenous leukemia in sickle cell anemia. Arch Pathol Lab Med. 2005;129(3):423-424. doi:10.5858/2005-129-423-CMLISC

2. Brunson A et al., Increased risk of leukemia among sickle cell disease patients in California. Blood. 2017;130(13):1597-1599. doi:10.1182/blood-2017-05-78323.

3. Stankovic et al., Chronic myeloid leukaemia and sickle cell disease: could imatinib prevent vaso-occlusive crisis?. Br J Haematol. 2011;155(2):271-272. doi:10.1111/j.1365-2141.2011.08670.x