Sequential development of human herpes virus 8-positive diffuse large B-cell lymphoma and chronic myelomonocytic leukemia in a 59 year old female patient with hemoglobin SC disease

Abstract Hematolymphoid neoplasms, including lymphoma and myeloid neoplasms, can occur in patients with sickle cell disease (SCD) or equivalent hemoglobinopathy, but an underlying connection between the two conditions has yet to be fully determined. Herein, we report a unique case of sequential development of two separate hematolymphoid neoplasms, human herpes virus 8 (HHV8)-positive diffuse large B-cell lymphoma (DLBCL) and chronic myelomonocytic leukemia, in a 59 year-old African American female with hemoglobin SC disease. While etiology of immunodeficiency is unknown, the potential causes include hydroxyurea therapy, disease related immunomodulation, chronic inflammation, and relatively old age. The leukemia cells demonstrated profound trilineage dysplasia and harbored complex cytogenetic abnormalities with loss of chromosome 5q and 7q, which are often observed in therapy-related myeloid neoplasms. Besides the potential causes listed above, we propose that myeloid leukemia in this setting may result from genomic changes due to excessive hematopoietic replication triggered by a hemolysis-induced cytokine storm. While myeloid neoplasms in the setting of SCD seems to herald a dismal clinical outcome per the literature, the HHV8-positive DLBCL in our case was apparently indolent, opposing the current perception of its clinical outcome.