LAUSR

Dear Editor, Accumulating evidence suggests that monoclonal B cell lymphocytosis (MBL) is a precursor condition for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/ SLL). Other MBL-derived B cell malignancies are quite rare, and the clonal evolution process and clinical implications remain unclear. Here, we describe a case of MBL-derived plasma cell leukemia (PCL) that developed during chemotherapy for SLL. An 82-year-old woman with a 20-year history of cold agglutinin disease treated with oral prednisolone began to experience difficulty walking due to dizziness. Laboratory examination showed a hemoglobin level of 4.7 g/dL and an IgM level of 1074 mg/dL with a cold agglutinin titer of 1:65536. Bone marrow examination revealed infiltration of small-tomoderate atypical lymphocytes which were positive for CD5, CD19, CD20, CD23, and smIgM, and negative for CD38, cyIgM, cyclinD1, and light chain restriction (Fig. 1a and b). Due to a peripheral blood (PB) lymphocyte count of < 5.0 × 10/L and no palpable lymph nodes, liver, and spleen, she was diagnosed with MBL that developed during immunosuppressive therapy. Although rituximab monotherapy (375 mg/m every week for 4 weeks) was transiently effective for hemolytic anemia, the condition relapsed 3 months later. Radiographic examination revealed both para-aortic lymphadenopathy and splenomegaly, leading to a diagnosis of SLL. Four cycles of combination therapy with rituximab, cyclophosphamide, and dexamethasone (RCD) halted the progression of hemolytic anemia. However, by the fifth cycle, PB leukocyte count suddenly increased to 22.8 × 10/L with 52% plasma cells which were positive for CD19, CD38, cyIgM, and kappa light chain restriction (Fig. 1c and d), and IgM PCL was diagnosed. Multiplex polymerase chain reaction (PCR) demonstrated identical immunoglobulin heavy chain gene rearrangement betweenMBL and PCL cells (Fig. 1e), indicating PCL originated from an MBL clone. Despite combination therapy with bortezomib, melphalan, and prednisolone, circulating plasma cell number and serum IgM level continued to increase. Eventually, the patient developed heart failure and was referred for palliative care. MBL, defined by the presence of a clonal CLL/SLL immunophenotype population in PB with a count of < 5.0 × 10/L, is present in 5–10% of healthy individuals older than 40 years, and one third ofMBL patients develop CLL/SLL [1, 2]. While most CLL/SLL cases are thought to be preceded by anMBL phase [3], progression to other B cell neoplasms is an unusual event. Additionally, although there have been cases of CLL/SLL and plasma cell neoplasms occurring concomitantly in a single patient, cases derived from the same cell of origin are even more rare [3–10]. This is the first report describing a case of sequential development of SLL and PCL originating from the same MBL clone during immunochemotherapy. Although the stage at which MBL to SLL plasmacytic transformation occurred remains to be determined, when considering the efficacy of RCD for SLL, eradication of the SLL population by RCD immunochemotherapy may have caused * Mineo Kurokawa [email protected]