Plasma Cell Leukemia with Myelofibrosis

Abstract

Myelofibrosis, which is usually observed as one of the primary forms of chronic myeloproliferative disorders, is characterized by splenomegaly and fibrotic bone marrow. The disease is observed in 10 to 30% patients with multiple myeloma. The degree of the marrow fibrosis tends to correlate with the magnitude of plasma cell infiltration and therefore seems to be associated with prognostic significance. On the other hand, plasma cell leukemia which is an infrequent manifestation of multiple myeloma develops in 12% of patients with multiple myeloma. Therefore, it seems to be a very rare case to observe the coexistence of plasma cell leukemia and myelofibrosis in the same stage of disease. Moreover, it has not been clearly demonstrated whether coexistent of myelofibrosis in untreated bone marrow with plasma cell leukemia is dependent on the secondary effect of this leukemia. Here, we report a case of plasma cell leukemia with myelofibrosis, which showed a rapid development into a fatal outcome. A 59-year-old man was admitted to our hospital because of fever and progressive general fatigue on July 2, 2000. The patient had remained asymptomatic until 3 months prior to his hospitalization. The findings on admission showed that the abdomen was slightly distended and both the liver and spleen were palpable at about 8 cm below the costal margin. Laboratory findings were as follows : white blood cells, 5.1 × 10/L (myelocyte, 0.5% ; metamyelocyte, 0.5% ; neutrophil, 37.0% ; lymphocyte, 25.5% ; monocyte, 16.0% ; plasma cell, 20.5% ; and erythroblast, 2.0%) ; hemoglobin, 6.5 g/dL ; platelets, 27 × 10/L ; lactate dehydrogenase (LDH), 1,875 IU/L ; calcium, 4.9 mEq/L ; albumin, 3.0 g/dL ; uric acid, 12.4 mg/dL ; BUN, 20.3 mg/dL ; creatinine, 1.5 mg/ dL ; CRP, 1.7 mg/dL ; b 2-microglobulin, 15.9 mg/dL ; IgG, 5,060 mg/dL ; IgA, 6 mg/dL ; and IgM, 6 mg/dL. Immunoelectropheresis revealed a monoclonal component of IgG l in the patient’s serum. X-rays of cranial and appendicular bones presented no punched out lesions. Abdominal computed tomography scan showed marked hepatosplenomegaly. A bone marrow aspiration was dry tap. A bone marrow biopsy showed marked myelofibrosis (Fig. 1) and infiltration of plasma cells, which manifested the same phenotype as circulating plasma cells in peripheral blood. Immunophenotypic analysis showed that plasma cells were positive for CD38, CD40, CD44, CD49d, and CD54, and negative for CD19, CD20, CD49e, CD56, CD62L, CD126, and HLA-DR. Chromosomal study using peripheral blood revealed complex karyotypic abnormalities such as 41, X, -Y, +1, der(1;3)(3pter → 9q27?, 1p11 → 1qter), der(1;17)(q10; q10), der(3)t(3;7)(q27;q11), ins(3;?)(q27;?), del(5)(q?), -7, 8, der(8)t(1;8)(p13;q24), -10, -13, -16, -22, +mar1, +mar2, and +mar3 in all 20 analyzed cells. Based on these laboratory data, the patient was diagnosed as having plasma cell leukemia with myelofibrosis. After the patient received combination chemotherapy consisting of vincristine (0.4 mg/body day 14), doxorubicin (15 mg/body, day14), and dexamethasone (40 mg/body, day 14), the circulating plasma cells gradually decreased. However, he died of acute renal failure, possibly due to tumor lysis syndrome and myeloma kidney on day 14. Plasma cell leukemia is characterized by the existence of the increased numbers of plasma cells both in peripheral blood and common organ sites (tissue infiltration), and the prognosis of this disease is very poor. This leukemia, which is defined as a condition that circulating peripheral blood plasma cells exceeding 2 × 10/L or 20% of peripheral blood white cells, is classified into two groups ; the “primary” and the “secondary” plasma cell leukemia. The secondary plasma cell leukemia is usually observed as a terminal complication during the course of multiple myeloma. Although it is widely accepted that there is a relationship between multiple