Response of hairy cell leukemia to bendamustine

A 47-year-old male was diagnosed with hairy cell leukemia (HCL) in 1998 after presenting with pancytopenia and splenomegaly. Peripheral blood smear, bone marrow, and flow cytometry were diagnostic of HCL, with bright positivity for CD20, CD22, CD11c, CD25, and FMC7, and positive staining for CD19, CD123, CD103, and lambda light chain. He did not respond to a 7-day cycle of cladribine and subsequently underwent splenectomy followed by rituximab, both without response. He achieved a clinical remission with pentostatin lasting 5 years. He relapsed and received multiple courses of pentostatin over several years before progressing and becoming refractory to pentostatin, 10 years after the initial diagnosis. He became transfusion-dependent for both blood and platelets, with neutrophil count 400/mm, platelet count 13 000/mm, and hemoglobin 8.7 g/dL, and bone marrow replaced with HCL. Computed tomography (CT) showed no peripheral but extensive retroperitoneal lymphadenopathy. He began eight cycles of bendamustine 90 mg/m days 1 and 2, every 4–7 weeks. Delays of retreatment were related to infections but not cytopenias worse than baseline. He became transfusion-independent after cycle 3, and achieved a partial response lasting 6 months. Bone marrow biopsy after cycle 7 showed about one-third of the marrow involved. The circulating HCL cell count decreased from 730/mm just after cycle 1 to 12/mm prior to cycle 3, and was 2/mm at 1 month after cycle 8. Although this patient did not respond to initial cladribine, characterization of his HCL cells, including positivity for B-cell markers, CD103, CD25, and CD123, was consistent with classic HCL based on the World Health Organization (WHO) definition [1]. Using 1:1 conjugates assessed by flow cytometry and control beads as described [2], the numbers of sites/cell on the HCL cells were 70 000 for CD20, 30 000 for CD22, and 4300 for CD25. Molecular characterization of the HCL cells [3] showed them to express the VH3-30-3 immunoglobulin heavy chain variable (IGHV) rearrangement, with 96.28% homology to germline. Analysis in the region of the third complementarity determining region (CDR3) of the heavy chain showed usage of IGHD3-22 and IGHJ4. To determine whether bendamustine would resolve the patient’s cytopenias or only worsen them by further myelosuppression, blood counts were assessed before each cycle and at multiple time points in between. As shown in Figure 1(B), the platelet count appeared erratic at first due to multiple platelet transfusions required, but platelet transfusions were not needed after cycle 3, and the platelet count rose to a maximum of 193 prior to cycle 7. Similarly, as shown in Figure 1(C), red cell transfusions were not needed after cycle 3 day 2 (C3D2) and the hemoglobin (Hgb) exceeded 10.0 after cycle 7. As shown in Figure 1(A), the neutrophil count did not resolve to the normal range during treatment with bendamustine, but did meet established criteria for partial response (PR) with respect to 50% improvement from baseline independent of transfusions or colony stimulating factors [4,5].