B-lymphoblastic leukemia in a patient with chronic lymphocytic leukemia: Sequential development of biclonal B-cell neoplasms over a 23-year period in a single individual

Abstract Chronic lymphocytic leukemia (CLL) is an indolent mature B-cell neoplasm. During a prolonged disease course, a secondary B-cell neoplasm may arise in some patients, the most common example being the clonal evolution of CLL to diffuse large B-cell lymphoma, which is referred to as Richter transformation. Secondary de novo mature B-cell neoplasms arising in a patient with pre-existing CLL have been described; however, B-lymphoblastic leukemia (B-ALL) developing in untreated CLL is rare, and its clonal relationship to the primary neoplasm has been an interesting issue. Herein, we report an unusual case of the sequential development of CLL and B-ALL over a 23-year period in a 64-year-old male. Examination of the peripheral blood smear and bone marrow biopsy demonstrated dual neoplastic populations: small mature lymphocytes consistent with those seen in CLL and a population of blasts that were confirmed to be B-ALL by immunophenotyping. The biclonality of these two B-cell neoplasms was supported by cytogenetic studies. While an intrinsic immunodeficiency in patients with CLL may predispose them to the development of other malignancies, the pathogenesis of this unusual phenomenon remains to be further investigated.