Adverse Outcomes in Concurrent Sickle Cell Disease and Hematological Malignancies

Introduction:

Case reports have suggested that there is an increased risk of hematological malignancies with sickle cell disease (SCD). We aimed to investigate the prevalence and mortality of select hematological malignancies, including: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), polycythemia vera (PV), essential thrombocytopenia (ET), Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL), primary myelofibrosis (PMF) in patients hospitalized with SCD.

Methods:

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample to identify the hospitalizations with SCD using ICD-9 codes 282.6, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, 282.69 from 1999 to 2014. Cases were then stratified based on the concurrent presence of the above hematological malignancies. The percentages of patients with each type of hematological malignancy were obtained using Chi-square analysis. In addition, we compared outcomes between patients with and without SCD who had hematological malignancies. Bivariate analysis for in-hospital mortality percentage was performed using Chi-square test. Multivariate analysis to evaluate the risk of death during hospitalization was performed using Cox proportional hazard regression with alpha set at 0.05.

Results:

There were 307,424 admissions (weighted=1,513,168) with SCD. Within these admissions, 0.04% (n=516) were associated with AML, 0.05% (n=720) with HL, 0.02% (n=47) with ALL, 0.07% (n=1,028) with NHL, 0.69% (n=10,654) with ET, 0.01% (n=20) with PMF and 0.01% (n=18) with PV. The hazard ratio for mortality (95% C.I.) with SCD compared to without SCD was 3.60 (1.24-4.67) for AML (p <0.001), 4.56 (2.78-6.78) for ET (p <0.001), 2.37 (1.41-5.67) for NHL (p=0.003), 1.5 (0.8-4.5) for HL (p=0.08), 1.1 (0.5-3.2) for ALL (p=0.04), 1.3 (1.1-3.2) for PMF (p= 0.03) and 1.7 (0.6-2.9) for PV (p=0.05).

Discussion:

The most frequently encountered hematological malignancy in patients with SCD was ET, followed by NHL and then HL. After controlling for multiple confounders including age, race, sex, comorbidities and socioeconomic status, the hazard of death during hospitalization with SCD, ET, AML, NHL and ALL are significantly higher compared to those without SCD.

While uncommonly encountered, concomitant hematological malignancy and SCD portends a significantly worse outcome, particularly in ET and AML. Potential explanations include iron overload from prior transfusions, increased infection risk due to asplenia and vascular damage from previous vaso-occlusive events. Newer advances in the management of SCD might improve subsequent outcomes in hematological malignancies.