Diagnosis and treatment of macrocytic anemias in adults.

Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL). Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia. Megaloblastic anemia is caused by deficiency or impaired utilization of vitamin B12 and/or folate, whereas nonmegaloblastic macrocytic anemia is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and by less commonly inherited disorders of DNA synthesis. Macrocytic anemias are treated with cause-specific therapies, and it is crucial to differentiate nonmegaloblastic from megaloblastic anemia. Because MDS and myeloid neoplasms commonly affect the elderly, primary care physicians may encounter more cases of macrocytic anemias in the near future, as the older population increases. When MDS is suspected along with leukocytopenia and/or thrombocytopenia with anemia, a hematology consultation may be appropriate.

Dasatinib-responsive chronic lymphocytic leukemia in a patient treated for coexisting chronic myeloid leukemia.

We herein present a case of concurrent chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Two different clones, a Philadelphia (Ph) clone and a CLL clone with a 13q deletion, were identified using fluorescent in situ hybridization. Dasatinib was administered to inhibit Bcr-Abl and Lyn kinase. The patient exhibited a molecular response for CML and a partial response for CLL. To our knowledge, this is the first report to describe the occurrence of a gradual increase in the Bcr-Abl transcript level prior to the diagnosis of Ph-positive CML in an individual with CLL who was successfully treated with dasatinib as the first-line therapy.

Safety and efficacy of low-dose liposomal amphotericin B as empirical antifungal therapy for patients with prolonged neutropenia.

BACKGROUND: Liposomal amphotericin B (L-AmB) is recommended as an empirical antifungal treatment for patients at increased risk of fungal infections although renal toxicity remains a clinical problem. We therefore conducted a pilot study to evaluate the safety and efficacy of low-dose L-AmB as an empirical antifungal therapy for patients with prolonged neutropenia. METHODS: High-risk patients with hematological malignancies were eligible to enroll in this study provided they had: exhibited neutropenia for at least 1 week; suffered from high-grade fever for 4 days despite treatment with a broad-spectrum antibacterial; and no identified fever-causing pathogen. Low-dose L-AmB (1 mg/kg) was administrated as empirical antifungal therapy. RESULTS: Sixteen patients were registered and, of these, data from the13 patients who did not receive allogeneic stem cell transplantation were analyzed. The median duration of low-dose L-AmB treatment was 8 days. Hypokalemia was seen in one patient: administration of potassium supplements for 10 days restored potassium levels to the normal range. A two-fold increase in creatinine levels was not found in any patients even those taking concomitant nephrotoxic drugs (e.g., amynoglycoside) during the study. One patient stopped receiving the drug due to an infusion-related adverse event. No patients showed breakthrough fungal infections or died during therapy or within 7 days after the end of the study. Increase in the L-AmB dose was necessary due to persistent fever in three patients who withdrew from the study. The satisfactory response rate for low-dose L-AmB was 69 %. CONCLUSION: This study suggests that low-dose L-AmB may be an effective option as empirical antifungal therapy for high-risk patients with febrile neutropenia.

[Adult T-cell leukemia-lymphoma developed from an HTLV-1 carrier during treatment of B-cell lymphoma-associated hemophagocytic syndrome].

A 63-year-old woman was admitted to our hospital with high-grade fever, liver dysfunction, and pancytopenia. Computed tomography of the whole body revealed hepatosplenomegaly but no lymphoadenopaties. Bone marrow aspiration showed infiltrations of CD20-positive large atypical B-lymphocytes with severe hemophagocytosis. Although she was a human T-cell leukemia virus type 1 carrier, the atypical lymphocyte in bone marrow had IgH rearrangement but not TCR rearrangement. From these clinical and laboratory data, the patient was diagnosed as having B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) and treated with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). After 4 cycles of R-CHOP, she had achieved complete remission. However, increased numbers of CD4+CD25+ flower cells were observed in peripheral blood and HTLV-1 provirus DNA was detected after 5 cycle of R-CHOP. The patient was diagnosed as adult T-cell leukemia-lymphoma (ATL) complicated by B-LAHS. Our observations suggest that continuous immunosuppressive statement for B-cell lymphoma or the chemotherapy against B-LAHS may induce the development of ATL in an HTLV-1 carrier.

Successful treatment of necrotizing fasciitis in an upper extremity caused by Clostridium perfringens after bone marrow transplantation.

We report a 47-year-old man with acute leukemia who survived a severe case of necrotizing fasciitis caused by Clostridium perfringens involving his right upper extremity. On day 5 after stem cell transplantation, progressive local tissue necrosis led to septicemia and disseminated intravascular coagulation. Early diagnosis and prompt initiation of appropriate therapy, including surgical debridement and broad-spectrum antibiotics, were crucial. A recombinant thrombomodulin might have not only resolved the coagulation problem but also prevented multiple organ failure associated with the systemic inflammatory response.