Charis Matsouka

Treatment of Waldenstrom's macroglobulinemia with thalidomide

PURPOSEnWe performed a prospective phase II study to assess the activity of thalidomide in patients with Waldenstroms macroglobulinemia (WM).nnnPATIENTS AND METHODSnTwenty patients with WM were treated with thalidomide at a starting dose of 200 mg daily with dose escalation in 200-mg increments every 14 days as tolerated to a maximum of 600 mg. All patients were symptomatic, their median age was 74 years, and 10 patients were previously untreated.nnnRESULTSnOn an intent-to-treat basis, five (25%) of 20 patients achieved a partial response after treatment. Responses occurred in three of 10 previously untreated and in two of 10 pretreated patients. None of the patients treated during refractory relapse or with disease duration exceeding 2 years responded to thalidomide. Time to response was short, ranging between 0.8 months to 2.8 months. Adverse effects were common but reversible and consisted primarily of constipation, somnolence, fatigue, and mood changes. The daily dose of thalidomide was escalated to 600 mg in only five patients (25%), and in seven patients (35%), this agent was discontinued within 2 months because of intolerance.nnnCONCLUSIONnOur data indicate that thalidomide has activity in WM but only low doses were tolerated in this elderly patient population. Confirmatory studies as well as studies that will combine thalidomide with chemotherapy or with rituximab may be relevant.

WALDENSTRÖM'S MACROGLOBULINEMIA

Waldenstroms macroglobulinemia (WM) is a lymphoproliferative disorder characterized by the presence of monoclonal lymphocytes that produce monoclonal immunoglobulin M (IgM). This disease was originally described in 1944 by Jan Waldenstrom, who reported two patients with long-standing oronasal bleeding, mild generalized lymphadenopathy, significant anemia, elevated erythrocyte sedimentation rate, very high serum viscosity, and low levels of fibrinogen. Large amounts of a high-molecular-weight globulin were detected in the serum of these patients, and their bone marrow aspirate revealed increased numbers of lymphocytoid cells. 127 The abnormal serum globulin was subsequently identified as an immunoglobulin and was called immunoglobulin M. Under the diagnosis of Waldenstroms macroglobulinemia are included patients with a low-grade lymphoplasmatic disorder associated with various amounts of serum monoclonal IgM. Some individuals, however, have a monoclonal IgM of undetermined significance without symptoms, without organomegaly or lymphadenopathy, and without anemia or evidence of bone marrow infiltration by the lymphoma. Such individuals do not require treatment, but some may develop overt WM. 68 Waldenstroms macroglobulinemia is a rare disease. Herrinton and Weiss reported an age-standardized annual incidence rate of 6.1 cases/million in white men and 2.5/million in white women. This disease is much more common in whites than in blacks. 55 Groves et al found that the age-adjusted incidence rates for WM/1 million person-years at risk were 3.4 among men and 1.7 among women. The rates increased sharply with age, from 0.1 at ages under 45 years to 36.3 at ages over 75 years for men. The rates for WM are comparable with those for hairy cell leukemia but are considerably lower than those for multiple myeloma or chronic lymphocytic leukemia. 49

Intravenous iron alone is equally effective with the combination of iron and erythropoietin for the treatment of iron-deficiency anemia in advanced heart failure.

To the Editor:nnThe prevalence of anemia in patients with New York Heart Association (NYHA) functional class IV heart failure (HF) approaches 80% ([1][1]). Iron deficiency (ID) has been reported as the cause of anemia in more than 70% of advanced HF patients ([2][2]). The underlying mechanisms of ID

Mantle-Cell Lymphoma (Multiple Lymphomatous Polyposis) of the Entire GI Tract

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Relapse of Ovarian Cancer With Bone Marrow Infiltration and Concurrent Emergence of Therapy-Related Acute Myeloid Leukemia: A Case Report

Case Report A 46-year-old woman was admitted to our hospital because of anemia and thrombocytopenia. Seven years before admission, she was diagnosed with epithelia ovarian cancer (International Federation of Gynecology and Obstetrics stage IIIC) and was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy (suboptimal debulking) followed by six courses of paclitaxel and carboplatin (total dose 1,800 mg and 4,500 mg, respectively), which resulted in a complete clinical response. Three months after chemotherapy she underwent an autologous transplantation using cyclophosphamide (4 g/m) and granulocyte colony-stimulating factors for mobilization and high-dose melphalan (180 mg/m) as conditioning regimen. Until recently, she was without evidence of disease. On admission her peripheral blood count status was as follows: hemoglobin 8 g/dL, WBCs 7.4 10/L (2% blasts, 62% neutrophils, 32% lymphocytes, 4% monocytes), and platelets 81 10/L. A bone marrow aspiration revealed hypercellularity, 20% blasts (Fig 1, black arrows) with Auer bodies and congregations of ovarian cancer cells (large epithelial cells with multiple nuclei and basophilic cytoplasm; Figs 1 and 2, white arrows). Immunophenotyping and flow cytometric analysis revealed that the blasts expressed myeloid antigens CD34, CD33, and CD117. Immunochemistry on trephine biopsy specimen recorded bone marrow infiltration by cells of epithelial origin. Conventional chromosome analysis showed a complex hypodiploid karyotype with monosomy 5, 18, and 21 (44 45, XX, 1, 5, 18, 21, add[21][p11], r, 3mar). CA125 was raised to abnormal levels, whereas chest and abdominal computed tomography scans did not show any lesions. A diagnosis of acute myeloid leukemia (AML; WHO classification) and concurrent ovarian cancer relapse with bone marrow infiltration was made. An AML-oriented chemotherapy with idarubicin (12 mg/m/d for 3 days) and cytarabine (200 mg/m/d for 7 days) was initiated. The disease proved to be refractory to chemotherapy and the patient died 6 months later, despite the administration of high-dose cytarabine (3 g/m for 3 days) as salvage therapy.