[Development of severe aplastic anemia during steroid therapy for autoimmune hemolytic anemia].

A 50-year-old male patient was admitted for close monitoring of anemia (hemoglobin level, 5.0 g/dl). Autoimmune hemolytic anemia (AIHA) of warm type was diagnosed based on the elevated reticulocyte and bone marrow erythroblast counts, elevated indirect bilirubin level, serum haptoglobin level below the detection limit, and positive direct Coombs test result.

[Acquired hemophilia A accompanied by immune thrombocytopenia].

A 72-year-old man was hospitalized because of thrombocytopenia (0.5×10/µl) and anemia. The bone marrow test result revealed excessive numbers of megakaryocytes and no platelet adhesion.

[The Usefulness of a Pamphlet for Preventing Exposure to Antineoplastic Agents at Cancer Patients' Homes and an Awareness Survey for Pharmacists about Providing Information to Cancer Patients about Exposure to Antineoplastic Agents].

As the number of patients undergoing outpatient chemotherapy has increased, there is concern that cancer patients' family members are unknowingly exposed to antineoplastic agents at home through cancer patients' excrement or other secreted materials. In this study, we created a pamphlet that introduces several methods to prevent exposure to antineoplastic agents at home and conducted a questionnaire survey to assess the usefulness of the pamphlet. The results indicated that more than 90% of patients believed that the pamphlet was "useful" or "very useful" for ensuring safety with respect to antineoplastic agents at home.

[Sudden blast crisis of chronic myeloid leukemia after a 13-year durable remission following allogeneic bone marrow transplantation and donor lymphocyte infusion].

We describe a rare case of sudden blast crisis of chronic myeloid leukemia that occurred after a 13-year durable remission, following allogeneic bone marrow transplantation and donor lymphocyte infusion. A 55-year-old Japanese man was diagnosed with chronic-phase chronic myeloid leukemia 24 years previously. He underwent allogeneic bone marrow transplantation 2 years after diagnosis.

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib.

Background: Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP).

Results: We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily.

Genetic variants in C5 and poor response to eculizumab.

Background: Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH). The molecular basis for the poor response to eculizumab in a small population of Japanese patients is unclear.

Methods: We assessed the sequences of the gene encoding C5 in patients with PNH who had either a good or poor response to eculizumab.

Marked upregulation of Survivin and Aurora-B kinase is associated with disease progression in the myelodysplastic syndromes.

Background: Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Survivin is a member of the inhibitor of apoptosis family and suppresses apoptosis. Survivin also functions as a subunit of the chromosomal passenger complex for regulating mitosis with Aurora-B.

Urinary pseudouridine in patients with lymphoma: comparison with other clinical parameters.

Background: Some patients with malignant lymphoma do not manifest superficial lymphadenopathy. In such cases, clinical parameters that indicate the number of tumor cells are important for the assessment of tumor growth and choice of proper treatment. We evaluated urinary pseudouridine (U-PU) as an indicator of the growth of malignant lymphoma by comparing its levels with serum concentrations of other clinical parameters in patients with various lymphomas at various stages.

[Cyclosporine A as an effective treatment for a patient with acquired hemophilia A complicated with diabetes mellitus and ischemic heart disease].

Acquired hemophilia A (AHA) is a rare coagulation disorder due to the development of an autoantibody against and inhibitor of coagulation factor VIII. It has been reported that immunosuppressive therapy with corticosteroids, cyclophosphamide, azathioprine and vincristine are effective to decrease this inhibitor. When corticosteroids and cytotoxic drugs are ineffective, cyclosporine A (CyA) may be effective as a second-line salvage therapy.

[Successful salvage therapy of continuous low-dose irinotecan for a patient with relapsed and refractory diffuse large B-cell lymphoma].

A 46-year-old man with relapsed and refractory diffuse large B-cell lymphoma after salvage therapy (EPOCH and ESHAP regimens) was treated with continuous low-dose CPT-11 (irinotecan hydrochloride) at 30 mg/day (20 mg/m2/day) for three consecutive days every week. The patient's general condition and both LDH and CRP, tumor related markers, improved dramatically. Complete remission was achieved after a 10-week cycle of therapy without severe adverse effects.

Association of Epstein-Barr virus with human immunodeficiency virus-negative peripheral T-cell lymphomas in Japan.

The association of Epstein-Barr virus (EBV) with human immunodeficiency virus-negative T-cell lymphoma was examined in 68 patients using the polymerase chain reaction (PCR) with DNA obtained from formalin-fixed paraffin-embedded tissues and an in situ hybridization technique. EBV-encoded RNA (EBER) was detected in 43 of 68 cases (63%) of peripheral T-cell lymphoma: in 100% (11 of 11 cases) of NK/T-cell lymphomas, 70% (14 of 20 cases) of angioimmunoblastic T-cell lymphomas (AILT) and 49% (18 of 37 cases) of other types of peripheral T-cell lymphoma. A positive band was also detected at high incidence (36 of 65 cases; 55%) in a PCR analysis using primers to detect the Bam HI-W fragment of EBV.

[Successful treatment with etoposide by oral administration for recurrence of gastric diffuse large B-cell lymphoma after surgical resection--a case report].

A 64-year-old woman, who had been treated for gastric diffuse large B-cell lymphoma (DLBCL) by total gastrectomy and received 3 courses of CHOP therapy at 61 years of age, was diagnosed with recurrence of DLBCL in the small intestine. After the small intestinal tumor was resected, multiple metastases were found in the liver. Because intensive chemotherapy was difficult for her poor performance status, 50 mg of etoposide daily by oral was administered for 21 consecutive days.

Incidence of diffuse large B-cell lymphoma of germinal center B-cell origin in whole diffuse large B-cell lymphoma: tissue fluorescence in situ hybridization using t(14;18) compared with immunohistochemistry.

Diffuse large B-cell lymphoma (DLBCL) can be divided into prognostically important categories such as germinal center B (GCB)-like and non-GCB-like groups. The t(14;18)(q32;q21) translocation defines a unique subset of DLBCL cases with a GCB gene expression profile. Two-color fluorescence in situ hybridization (FISH) analysis was applied to detect t(14;18) (q32;q21) in the nuclei of paraffin-embedded tissue sections from 61 patients with de novo DLBCL.

[Clinical significance of cevimeline hydrochloride in the treatment of dry mouth in patients with Sjögren's syndrome].

To evaluate the efficacy and safety of cevimeline hydrochloride for the treatment of dry mouth in patients with Sjögren's syndrome (SS), eight SS patients received 30 mg of cevimeline twice or three times daily for 24 weeks. Six out of the eight patients had improvement in dry mouth. Five patients had more than 20% increase in saliva secretion.

Analyses for binding of the transferrin family of proteins to the transferrin receptor 2.

Transferrin receptor 2 alpha (TfR2 alpha), the major product of the TfR2 gene, is the second receptor for transferrin (Tf), which can mediate cellular iron uptake in vitro. Homozygous mutations of TfR2 cause haemochromatosis, suggesting that TfR2 alpha may not be a simple iron transporter, but a regulator of iron by identifying iron-Tf. In this study, we analysed the ligand specificity of TfR2 alpha using human transferrin receptor 1 (TfR1) and TfR2 alpha-stably transfected and expressing cells and flow-cytometric techniques.

Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis.

Transferrin receptor 2 (TfR2) is a membrane glycoprotein that mediates cellular iron uptake from holotransferrin. Homozygous mutations of this gene cause one form of hereditary hemochromatosis in humans. We recently reported that homozygous TfR2(Y245X) mutant mice, which correspond to the TfR2(Y250X) mutation in humans, showed a phenotype similar to hereditary hemochromatosis.

Epstein-Barr virus-associated composite lymphoma composed of peripheral T-cell lymphoma and an anaplastic variant of a diffuse large B-cell type of non-Hodgkin's lymphoma and strongly expressing p53 protein.

We report a case of composite lymphoma consisting of peripheral T-cell lymphoma and an anaplastic variant of diffuse large B-cell lymphoma (DLBCL) and associated with Epstein-Barr virus (EBV) infection and strong p53 expression. A 65-year-old Japanese woman developed fever and generalized lymphadenopathy. A biopsy of the cervical node revealed the morphology of malignant lymphoma with 2 kinds of lymphoma coexisting in 1 lymph node.

['Reverse' variant of follicular lymphoma with monoclonality of the immunoglobulin heavy chain and T cell receptor gamma chain genes].

We report an unusual case of the 'reverse' variant of follicular lymphoma in which the nodules had central parts that stained dark and cuffs that stained pale. Because diagnosis was difficult relying only on formalin-fixed histopathology, we examined the cell surface markers and karyotype. The patient, a 65-year-old man, presented with multiple lymphadenopathy, low-grade fever, night sweats, anorexia, dry cough and sense of chest oppression.

Epstein-Barr virus-associated anaplastic large cell variant of diffuse large B-cell-type non-Hodgkin's lymphoma with concurrent p53 protein expression.

In the new World Health Organization (WHO) classification of malignant lymphoma, anaplastic large cell lymphoma of B-cell phenotype is classified either as the anaplastic large cell variant of diffuse large B-cell lymphoma or as Hodgkin's lymphoma. A 71-year-old Japanese man developed fever and generalized lymphadenopathy. Biopsy of the right axillary node revealed morphology of malignant lymphoma in which large cells with abundant cytoplasm and pleomorphic nuclei were scattered among small lymphocytes.

[Clinical significance of serum KL-6 and SP-D for the diagnosis and treatment of interstitial lung disease in patients with diffuse connective tissue disorders].

Objective: To elucidate the clinical significance of serum KL-6 and SP-D for the diagnosis and treatment of interstitial lung disease in connective tissue disorders.

Methods: 139 patients with various connective tissue disorders were subjected for the study, which included 46 cases of rheumatoid arthritis, 43 cases of Sjögren's syndrome, 16 cases of SLE, 10 cases of systemic sclerosis, 9 cases of polymyositis/dermatomyositis, 6 cases of vasculitis syndrome, 5 cases of Behçet's disease and 4 cases of MCTD. Serum levels of KL-6 and SP-D were determined by enzyme-immunoassay.

Expression of the antiapoptotic gene survivin in chronic myeloid leukemia.

Survivin, a unique member of the inhibitor of the apoptosis protein (IAPs) family, is over-expressed in many cancers but not in normal differentiated adult tissues. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we investigated patterns of survivin gene expression in a group of 12 patients with chronic myeloid leukemia (CML) representing both chronic and blastic phases of the disease. All 6 patients in chronic phase CML were uniformly negative for the survivin transcript, in contrast to 4 Philadelphia chromosome-positive (Ph+) CML patients in blastic crisis, all of whom (100%) were positive for survivin with tangible levels of expression.

Expression of the anti-apoptotic gene survivin in myelodysplastic syndrome.

Survivin is a member of the inhibitor of apoptosis protein (IAPs) family and considered to play a pivotal role in oncogenesis. We present the first report of survivin expression profile in myelodysplastic syndrome (MDS). Expression of survivin messenger RNA was evaluated by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with MDS and acute myeloid leukemia (AML).

Double Ph-positive megakaryoblastic transformation of chronic myeloid leukemia.

A 64-yr-old Japanese man presented with mild anemia, leukocytosis, and thrombocytosis in November 1999. A diagnosis of chronic myeloid leukemia was made with a positive Ph chromosome, and interferon alpha treatment was started, 6 million units a day. Two years later, in October 2001, the patient developed leukocytosis, an increased LDH level, and large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood.