Complete remission and successful stem cell mobilization after treatment of refractory plasma cell leukemia with bortezomib

Abstract

Dear Editor, Plasma cell leukemia (PCL) is a rare form of a plasma cell dyscrasia characterized by the presence of >2×10 plasma cells (PC)/L comprising >20% of circulating PC in the peripheral blood differential count [1]. The prognosis of PCL is generally poor and the median survival for patients with PCL infrequently exceeds 7 months [2]. High-dose chemotherapy followed by autologous stem cell transplantation is currently the most effective therapeutic tool to achieve durable remissions. Prior to the stem cell supported treatment, the collection of an apheresis product containing no or only a few plasma cells is mandatory to pursue this strategy. Here we report the case of a patient in which circulating plasma cells persisted during polychemotherapy and thalidomide treatment and then disappeared after two cycles of treatment with bortezomib allowing the collection of autologous stem cells. The patient was presented to us with multiple fractures of the spine, leukocytosis and a discrete paraproteinuria-type kappa. The peripheral blood smear showed 50% atypical leukocytes with similarity to plasma cells and a CD19CD45CD38CD56CD138 immunophenotype. The trephine bone biopsy showed a hypoplastic marrow with a 50% plasma cell infiltration. After four cycles of orally administered idarubicin and dexamethasone (ID), the proportion of the peripheral plasma cells was 26% (see Table 1). After the mobilization chemotherapy with ifosfamide, epirubicin and etoposide (IEV) and stimulation with granulocyte-colony stimulation factor (G-CSF), the proportion of circulating plasma cells was still 20% and therefore, no stem cell collection was feasible. Next, two cycles of cyclophosphamide, doxorubicine and dexamethasone plus thalidomide (T-CAD) were given. Unfortunately, there was no effective reduction of peripheral plasma cell count or bone marrow infiltration. After one further attempt with cyclophosphamide, adriamycine, dexamethasone, etoposide and cisplatin plus thalidomide (DT-PACE), we found only a marginal decrease of the plasma cell content in the bone marrow. Then, the decision for therapy intensification was made and the patient was treated according to the protocol for patients with acute lymphatic leukemia (ALL). This treatment induced a decrease of the peripheral plasma cell count to 4%, but no significant decrease of the bone marrow infiltration or of the serum parameters was seen. At this point a therapy with bortezomib was initiated as a final attempt. After two cycles of bortezomib the circulating plasma cells disappeared completely, after two further cycles the urinary light chains were no longer detectable. Additionally, the performance status of the patient improved during the therapy with bortezomib, whereas only slight side effects such as discrete lid edema and mild thrombocytopenia were noted. Subsequent mobilization chemotherapy with etoposide and cyclophosphamide followed by G-CSF plus erythropoetin led to a successful stem cell apheresis. The first high-dose chemotherapy with melphalan was made approximately 14 months after the diagnosis. At this point in time, the patient was already in complete remission according to the criteria published by Blade et al. [3]. Bortezomib is a modified dipeptidyl boronic acid that reversibly inhibits the chymotrypsin-like activity of the 26S proteasome of mammalian cells, which degrades specific proteins within the cell, and therefore induces cell death. Richardson et al. reported in 2003 on the use of bortezomib in patients with multiple myeloma, describing an overall response rate of 35% [4]. The use of bortezomib in a concentration of 1.3 mg/m in combination with dexamethasone resulted in an even higher overall response rate >50% [5]. A first report describing the efficacy of bortezomib in the treatment of PCL after high-dose chemotherapy followed by autologous stem cell transplantation J. Grassinger . T. Sudhoff . B. Hennemann (*) Department of Hematology and Oncology, University of Regensburg, 93042 Regensburg, Germany e-mail: burkhard.hennemann@klinik.uni-regensburg.de Tel.: +49-941-9445531 Fax: +49-941-9445511