Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are two distinct hematological malignancies thought to arise at different stages of the B cell maturation pathway.

Here, we aimed to present our approach to such a patient.

A 59-year-old male patient was examined for hematuria in 2019, lymphocytosis was detected, and flow cytometry (FC) was performed. The result was found to be compatible with CLL. The patient was evaluated as Binet A, Rai 0 at the diagnosis, and was followed without treatment.

In the fourth year of treatment-free follow-up, the patient developed severe B symptoms and widespread lymphadenopathies (LAP), splenomegaly (size 15.5 cm) on imaging, and shortened lymphocyte doubling time, so bone marrow aspiration biopsy (BMAB), FC and cytogenetic tests were performed. The patient had a CLL immunophenotype score of 1 in flow cytometry, and cytogenetics showed negative 17p del and TP53 mutations. In BMAB, 80% atypical morphology and immunohistochemical (IHI) examination showed small lymphoid cells with CD19(+), CD20(+), CD23(+), and CD5(+) staining. The patient was evaluated as Binet B, Rai 2, and got 6 cycles of Chemoimmunotherapy (Rituximab, Fludarabine, Cyclophosphamide). After treatment, B's symptoms regressed, and LAP and splenomegaly returned to normal.

The patient developed neutropenia requiring granulocyte colony-stimulating factor (G-CSF) during follow-up, therefore, the patient underwent repeat BMAB. In the result, plasma cells with intense kappa positive staining were observed, and in the IHI examination, the CD38 and 138 positivity rates were evaluated as 20%. The patient, who did not have hypercalcemia, renal dysfunction, anemia, bone lesions, and extramedullary involvement, was assessed as MGUS, neutropenia resolved spontaneously during follow-up, and it was decided to follow the patient at three-month intervals without treatment.

MM and CLL were rare in the same patient, and there is limited information regarding clinical outcomes and management. The clonal relationship between them is controversial.