We retrospectively investigated the clinical characteristics of reactivation of hepatitis B (HB) virus after allogeneic hematopoietic stem cell transplantation (HSCT). Of 2002 patients who received transplantation between January 1994 and December 2004, seven patients who were anti-HB surface antibody (anti-HBs) positive and HB surface antigen (HBs-Ag) negative developed reactivation of the HB virus after allogeneic HSCT. The patients' median age was 49 years, and they consisted of 5 males and 2 females. Six of 7 recipients received hematopoietic stem cells from HLA-identical sibling donors. All donors were negative for HBs-Ag. Six donors were negative for anti-HBs and one donor was not investigated for anti-HBs. HB reactivation occurred 5 to 29 (median 15) months after HSCT. Chronic graft-versus-host-disease (GVHD) was observed in 5 cases. The peak value of GPT during HB reactivation varied from 83 to 1930 (median 318) IU/l. Lamivudine was given to 5 patients. One patient was treated with supportive therapy and other one patient was observed without treatment. Two patients developed fulminant hepatitis and died of hepatic dysfunction. Clinicians should consider the possibility of HB reactivation in anti-HBs-positive patients. The establishment of a preventive method for HB reactivation would be desirable.

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It has been reported in the Western literature that patients with chronic renal disease have developed anti-erythropoietin (EPO) antibody-related pure red cell aplasia (PRCA). To investigate the incidence of anti-EPO antibody-related PRCA in Japan, we designed a questionnaire survey based on previous reports of patients who had PRCA during treatment with EPO. Thirteen of 17 patients were evaluated in this study. In all 13 patients, EPO delivery was via injection, 9 subcutaneously, 2 intravenously and 2 with a combination of the 2 methods. Three of 4 patients treated with subcutaneous EPO administration were positive for anti-EPO antibodies, but all patients treated by intravenous injection were negative. The EPO was stopped in 8 patients after the onset of PRCA, and immunosuppressive therapy with prednisolone and/or cyclosporine was administered in 12 patients. An improvement in PRCA was obtained in 12 patients. It was suspected that previous reports in Japan may have included both anti-EPO antibody-associated PRCA and incidental cases. Furthermore, subcutaneous administration of EPO may effect the production of anti-EPO antibodies.

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A 56-year-old Japanese woman was admitted to our hospital with upper abdominal pain. Gastroendoscopy revealed a Borrmann III type tumor which was diagnosed from the biopsied specimen as an anaplastic large cell lymphoma (ALCL). CT scan revealed para-aortic and left-supra clavicular lymph node swelling, so her clinical stage was defined as IIIE according to the Ann Arbor classification. The patient first of all received CHOP therapy, however her lymphoma lesions increased in size. Therefore she underwent salvage chemotherapy regimens and autologous peripheral blood stem cell transplantation (APBSCT). She has remained in complete clinical remission (CCR) for eleven months after the APBSCT.

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We report on 4 children with invasive fungal infections complicated with leukemia who responded to voriconazole (VRCZ). In 3 children aged 1-6 years, the plasma VRCZ concentration was low and clinically ineffective after its administration at a dose of 4 mg/kg. Good plasma concentrations could be attained by increasing the dose to 5.3-12 mg/kg, and clinical effects were observed. In the other 13-year-old male, an adequate plasma concentration could be obtained after VRCZ administration at a dose of 4 mg/kg. Concerning adverse effects, transient visual abnormality developed in only 1 child. VRCZ may be effective and safe not only in adults but also in children with invasive fungal infection during chemotherapy for leukemia. Though the dose in adults is 3-4 mg/kg, the dose/weight in children should be higher because of the greater clearance. Since there are also individual differences in drug metabolism, the dose in children should be individually adjusted based on the plasma concentration.

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A 75-year-old man was admitted to our hospital in October, 2005 for examination of pre-diagnosed pancytopenia. His bone marrow showed myeloid dysplasia, and 30.4% of the nucleated cells were blasts. Our diagnosis was acute myelogenous leukemia with multilineage myelodysplasia (AML with MLD; WHO classification). A direct Coombs test proved positive, and the platelet-associated IgG (PA-IgG) level was elevated. After treatment with CAG (Ara-C+ACR+G-CSF), complete remission was obtained, showing negative on the direct Coombs test with PA-IgG levels returned to normal. The patient subsequently relapsed, testing positive on the direct Coombs test and experiencing a re-elevation of PA-IgG levels. We report here a first case of AML with MLD, direct Coombs test and PA-IgG assay.

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A 59-year-old man was admitted to our hospital with a diagnosis of acute myeloid leukemia in September 2004. He developed invasive pulmonary aspergillosis (IPA) and candidiasis, which were improved by administration of micafungin and amphotericin B (AMPH-B). He received reduced-intensity unrelated cord-blood transplantation without induction chemotherapy. He developed grade IV graft-versus-host disease (GVHD) and the administration of steroids against GVHD was prolonged. Voriconazole (VRCZ) was used for a long period to prevent recurrence of the IPA. Afterwards, infiltrates in the bilateral upper lung fields were detected on a chest CT scan, and a diagnosis of pulmonary mucormycosis was made following detection of Mucor circinelloides from the patient's sputum culture. He then began receiving AMPH-B but died of massive hemoptysis. Mucormycosis usually occurs in immunocompromised hosts such as neutropenic patients with hematologic diseases and is a fatal fungal infection characterized by a rapid and progressive clinical course. Some overseas investigators have recently reported that VRCZ prophylaxis may result in breakthrough mucormycosis in hematopoietic stem cell transplant recipients. These findings suggest that it is very important to pay attention to mucormycosis in hematopoietic stem cell transplant recipients in this country.

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Congenital factor XIII (FXIII) deficiency is a rare congenital hemorrhagic disorder. Since FXIII is an essential factor in pregnancy, pregnant patients with congenital FXIII deficiency should receive adequate replacement of FXIII concentrate. We report here on a 19-year-old pregnant woman with congenital FXIII deficiency. Despite regular replacement of FXIII concentrate, FXIII activity decreased rapidly after 32 weeks of gestation and she had to receive a high-dose of FXIII concentrate until delivery. Careful monitoring of FXIII activity is needed in patients with congenital FXIII deficiency, because FXIII activity may decrease rapidly in late pregnancy.

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