Eur J Haematol 2001: 67: 51±53 Printed in UK. All rights reserved
Copyright # Munksgaard 2001 EUROPEAN JOURNAL OF HAEMATOLOGY
ISSN 0902-4441
Case report
Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone Christou L, Hatzimichael E, Chaidos A, Tsiara S, Bourantas KL. Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone. Eur J Haematol 2001: 67: 51±53. # Munksgaard 2001. Abstract: Primary plasma cell (PCL) leukemia is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in the bone marrow and peripheral blood. Survival with standard therapy using melphalan is very poor. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is at least as ef®cient and has fewer side effects than conventional doxorubicin. Two female patients (69 and 54 yr old) with primary PCL are described in this study. They both received a modi®ed form of VAD (vincristine, doxorubicin and dexamethasone), a regimen which includes liposomal doxorubicin (40 mg/m2 for 1 d), vincristine (2 mg for 1 d) and dexamethasone 40 mg per os on days 1±4, 9±12 and 17±20. A disease evaluation of the ®rst patient after six courses of the modi®ed \VAD regimen showed no plasma cells in the peripheral blood, a decrease in the serum M protein level and a plasma cell in®ltration in the bone marrow of less than 5%. The patient died from a cardiac episode 24 months post-diagnosis, while she was in complete hematological remission. The second patient also exhibited good tolerance to liposomal doxorubicin with no side effects, achieved complete haematological remission and remains in good condition 7 months after the last VAD administration. These results suggest that this modi®ed form of VAD regimen also seems to work in PCL and is well tolerated with no side effects.
Plasma cell leukemia (PCL) is a very rare plasma cell dyscrasia. It mainly occurs as a terminal event in the evolution of multiple myeloma in 1±2% of cases (secondary PCL), but it can also occur as a presenting feature (primary or de novo) (1). The incidence of primary PCL is estimated to be 1.6% of all myeloma cases (2). Owing to the low frequency of this entity, most publications are based on case reports and responses are anecdotal. Therefore, treatment of PCL is dif®cult to evaluate and remains disappointing. Up to now several treatment modalities have been used. Conventional melphalan-based treatments and single agents, such as ifosfamide, cyclophosphamide, ¯udarabine and BCNU (carmustine),
Leonidas Christou, Eleftheria Hatzimichael, Aristidis Chaidos, Stavroula Tsiara, Konstantinos L. Bourantas Haematology Clinic, Department of Internal Medicine, University of Ioannina Medical School, Ioannina, Greece
Key words: plasma cell leukemia; treatment; modi®ed VAD regimen; liposomal doxorubicin Correspondence: K. L. Bourantas, M.D., Professor of Internal Medicine-Haematology, P.O. Box 37, GR-45 002 Ioannina, Greece Tel: +30 651 24794 Fax: +30 651 39356 e-mail:
[email protected] or
[email protected] Accepted for publication 12 March 2001
failed to improve survival rates, which do not usually exceed 7 months (3±5). More intensive therapeutic approaches, mostly used for multiple myeloma (MM), such as the VAD regimen (vincristine, doxorubicin and dexamethasone) are giving more promising results (3, 6). In a previous study (7) we have described encouraging results of the administration of a modi®ed VAD regimen containing vincristine, liposomal doxorubicin and dexamethasone in patients with MM. Since no treatment of choice exists for patients with PCL, we administered this modi®ed VAD in two patients with primary PCL in order to investigate the safety and probable higher ef®cacy of this treatment. 51
Christou et al. Case reports
Criteria for the diagnosis of PCL were an absolute plasma cell (PC) count greater than 2r109/L, with PCs also comprising greater than 20% of peripheral blood cells (8), although according to others, these criteria are arbitrary (9). Complete remission was de®ned as disappearance of plasma cells in peripheral blood, a decrease of at least 50% in the serum M protein level (8) and a plasma cell in®ltration in the bone marrow of less than 5%. Patient 1
In April 1998 a 69-yr-old woman was admitted to the hospital because of fatigue, dyspnea and weight loss. Her past medical history, apart from hypertension, was unremarkable. Physical examination revealed pallor, lymphadenopathy but no other pathological signs. A complete blood count revealed a haemoglobin value of 9.13 g/dL, a haematocrit value of 29.3%, and a white blood cell count of 18.9r109/L with 35% plasma cells and platelets 264r109/L. A bone marrow aspirate revealed 55% in®ltration by typical plasma cells. The total serum protein was 90 g/L. Immunoelectrophoresis of serum revealed an M-component. Quantitative measurement revealed the following pathological values: IgG 35.2 g/L and k light chains 10.7 g/L. The urine was negative for Bence±Jones protein. Apart from diffuse osteopenia, a skeletal bone survey did not reveal osteolytic lesions. The concentration of serum calcium was within normal limits, but the patient had elevated urea and creatinine concentrations, 1770 mg/L and 51 mg/ L, respectively. Ultrasonography revealed small kidneys bilaterally, and a diagnosis of chronic renal failure was made. The patient began hemodialysis after an episode of pulmonary oedema. In the immediate follow-up a drop in the Hb value was noted and the diagnosis of primary plasma cell leukemia was made (IgG k, stage III) following the clinical staging system proposed by Durie and Salmon. At the time of diagnosis b2-microglobulin (b2M) was 32,959 mg/L. We administered a modi®ed VAD regimen as follows: vincristine 2 mg bolus IV, doxorubicin covered with liposomes (Caelyx1) 40 mg/m2 IV for 1 d (via a peripheral vein) and dexamethasone 40 mg orally on days 1±4, 9±12 and 17±20. An ECG and echocardiographic study of the ejection fraction were performed prior to liposome doxorubicin administration. The patient received six cycles of the abovementioned regimen. A disease evaluation after six courses of the modi®ed VAD regimen showed no plasma cells in the peripheral blood, decreased levels of b2M 52
(1316 mg/L), while the plasma cells in the bone marrow were less than 5%. A complete blood count revealed haemoglobin 9.4 g/dL, haematocrit 29.8%, white blood cell count 9.4r109/L and platelet count 236r109/L. The M-component disappeared in electrophoresis, and IgG and k light chain values were 7.3 g/L (normal range 8±17 g/L) and 2.54 g/L (normal range 2±4 g/L), respectively. For the next 12 months the patient was in good condition but she had to undergo hemodialysis twice a week. When her haemoglobin value was less than 8.5 g/dL, she was administered recombinant human erythropoietin 10,000 U/3 times weekly in combination with oral ferrum supplements. The patient died from a cardiac episode 2 yr postdiagnosis while in complete hematological remission. Patient 2
In January 2000 a 54-yr-old woman was admitted to our hospital because of acute renal failure, fever and severe anemia. She had a 2-month history of fatigue and anorexia, weight loss of 7 kg and anemia. Physical examination revealed pallor, petechiae and mild hepatosplenomegaly, while auscultation of the chest revealed coarse crackles. Chest x-ray demonstrated pulmonary in®ltrates, indicating pneumonia. Hematological data were as follows: hemoglobin 5.1 g/dL, haematocrit 17.4%, white blood cell count 28.7r109/L, platelets 109r109/L and ESR 92 mm in 1 h. The differential count showed 50% plasma cells. In the peripheral blood the phenomenon of hemophagocytosis was noted, with plasma cells having engulfed red blood cells or platelets. A bone marrow aspiration revealed a 60% in®ltration of typical plasma cells. The total serum protein was 100 g/L with an M-component. Quantitative measurement revealed the following values: IgG 3.42 g/L (normal range 8±17 g/L), IgA 55.4 g/L (normal range 0.85±4.4 g/L), IgM
