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Giant cell arteritis (GCA), a type of systemic arteritis, is rare in Japan. We herein report a case of acute myeloid leukemia (AML) complicated by GCA that manifested during chemotherapy for AML. A 77-year-old woman with severe back pain was diagnosed with AML. She achieved complete remission with the resolution of her back pain following induction chemotherapy. However, she developed a headache and fever after consolidation chemotherapy. A diagnosis of GCA was made based on a biopsy of the temporal artery and arterial imaging. GCA should therefore be included in the differential diagnosis in AML patients complicated with a headache and fever of unknown origin.

A diagnosis of acute promyelocytic leukemia (APL) is usually made when normal hematopoietic cells are substituted by APL cells. We encountered a unique APL patient who presented with persistent hypoplastic features of APL. An 84-year-old man presented with leukopenia (2.2 × 10(9)/L) and anemia (Hb 12.5 g/dL). Five months later, the bone marrow (BM) was hypoplastic with a normal proportion of blasts and promyelocytes (5.2%), although the latter cells were hypergranular. The karyotype of BM cells was 46, XY, t(15;17)(q22;q12), t(9;11)(q13;p13). Two months later, the BM remained hypoplastic with 8.5% hypergranular promyelocytes, some of which contained faggot of Auer rods. RT-PCR examination yielded the PML-RARα transcript, and its sequencing revealed the breakpoint of PML to be bcr2. The patient was treated with all-trans retinoic acid under a diagnosis of APL with improvement of the bicytopenia. FISH analysis of BM cells yielded a negative result regarding t(15;17), although RT-PCR was positive for PML-RARα mRNA. Six months later, APL recurred with the same karyotypic abnormalities and therapeutic resistance, and the patient died of pneumonia. A persistent hypoplastic state of APL may be a rare event, and the association of t(15;17) and t(9;11) is novel.

A 68-year-old female was diagnosed with acute myeloid leukemia (AML-M2 without 8/21 translocation) in December 2006. Although a complete remission (CR) was obtained after induction chemotherapy, the first post-remission therapy was discontinued because of severe cardiovascular complications. She had a relapse of AML with CD33-positive myeloblasts which comprised 38.4 % of the bone marrow cells in November 2007. She received two courses of low-dose chemotherapy because of the previous complications. The amount of Wilm's tumor 1 (WT1) mRNA in the peripheral blood was 13,000 copies/μg RNA after the first course of the chemotherapy, and 4.8 % myeloblasts remained in the bone marrow after the second course. She was treated with a single course of gemtuzumab ozogamicin (GO), with a subsequent CR with 0.9 % marrow myeloblasts and fewer than 50 copies of WT-1 mRNA (normal level). Thereafter, she received five courses of GO monotherapy at each occasion of early AML relapse. Hematological remission has been sustained over a period of about 24 months with the GO monotherapy alone. This case suggests that GO monotherapy is a useful salvage therapy for early relapse of CD33-positive AML in situations in which standard chemotherapy is not indicated.

The development of novel agents has markedly improved the prognosis of multiple myeloma(MM). However, salvage therapies for patients with MM that is refractory to novel agents and conventional chemotherapies have not been established. Herein, we describe successful treatments for such patients with the combination of clarithromycin, lenalidomide, and lowdose dexamethasone(BiRd)with or without melphalan and prednisolone(MP). Although its duration was relatively short, the remission is important in terms of the salvage strategy until the second generation of novel agents becomes available.

Purpose BACH2, a B-cell–specific transcription repressor, is abundantly expressed in lymphocytes of B-cell lineage as well as B-cell lymphoma cell lines. BACH2 possesses an inhibitory effect on proliferation of Raji cell lines derived from Burkitt's lymphoma. In this study, the prognostic significance of BACH2 expression was examined in diffuse large B-cell lymphoma (DLBCL). Patients and Methods BACH2 expression was immunohistochemically examined on the paraffin-embedded sections obtained by biopsy from 108 patients (62 males and 46 females; age range, 23 to 85 years) with DLBCL. Staining intensity in the cytoplasm of the tumor cells was categorized as equal to or stronger (level 1) or weaker (level 2) than that in the endothelial cells in the same specimens. Results Level 1 and 2 expression of BACH2 was found in 32.4% and 67.6% of patients, respectively. Patients with level 1 expression showed significantly better disease-free and overall survival rate than those with level 2 expression (both P < .05). Multivariate analysis revealed BACH2 expression level together with performance status, elevated serum level of lactate dehydrogenase, and treatment response to be independent factors for prognosis of the patients. Conclusion BACH2 expression level is a useful marker to predict disease-free and overall survival of patients with DLBCL.

Epstein-Barr virus (EBV) initially isolated from the cultured Burkitt lymphoma (BL) cells, is one of the well-known oncogenic virus. The NAB-2 line, which was established from a North American Burkitt's tumor, was indicated to contain one copy of EBV DNA as the integrated form into chromosome 2p13 of the host genome. To demonstrate the integration site of EBV directly, and to clarify the relation between the integration sites and the oncogenes, fragments containing the nucleotide sequence of NAB-2 integration sites were cloned. EBV was integrated via the terminal repeats (TR), and integration sites located in the clone RP11-440P5 on chromosome 2, between two oncogenes, REL and BCL11A, which is apart from approximately 350 kbp from each other. Expression level of REL in NAB-2 was increased. The flanking region of chromosome 2 at the bilateral junction sites showed no homology to the junction sites of EBV. The integration site 2p13 overlaps with common fragile site, FRA2E. NAB-2 cells expressed almost all latent genes but LMP-2A that flanks the TR, indicating the type III of latent infection of EBV. Integration event in NAB-2 might alter the regulation of the oncogenes and provide advantage for continuous cell proliferation.

We report a patient with aggressive systemic mastocytosis (SM), who exhibited eosinophilia and unusual destructive bone lesions. A 43-year-old female was referred to our hospital because of a vertebral compression fracture, multiple lytic bone lesions, and eosinophilia in February 2011. A diagnosis of aggressive SM was made on the basis of abnormal mast cells in the bone marrow, high serum tryptase levels, and multiple lytic bone lesions including vertebral compression fractures. Polymerase chain reaction and subsequent sequencing of its products to identify mutations of c-kit yielded negative results and imatinib mesylate failed to improve the SM of the patient. She was then treated with interferon-α, with considerable improvement of the disease, although severe myelosuppression prevented the continued administration of a sufficient dose of this agent. In August 2011, the patient suddenly developed paraplegia of the lower extremities. Magnetic resonance imaging demonstrated epidural mass lesions at the levels from Th9 to Th11, compressing the spinal cord. Emergent laminectomy and subsequent irradiation of the tumors were performed without improvement of the paraplegia. Histopathologic examination of the epidural tumors, from samples obtained intraoperatively, confirmed the diagnosis of SM. She was further treated with dasatinib and then cladribine without obvious improvement, although the latter reduced the eosinophilia to some extent ; however, she died of sepsis in September 2011.

A 47-year-old man was diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in October 2005. He could not receive treatment with imatinib mesylate due to his economic circumstances. He was consequently treated with hydroxyurea with partial hematological remission until June 2008. Although imatinib mesylate was started thereafter, the adherence to this treatment was poor because of his occupational circumstances. In September 2009, imatinib mesylate was switched to nilotinib, with a subsequent phase of acceleration of the disease, presumably due to his poor adherence to the treatment. Dasatinib was started in September 2010, with transient hematological response and final blastic crisis of the disease in January 2011, regardless of improved adherence. Blast cells showed immature monocytic morphology and were positive for α-naphtylbutyrate esterase staining. They also expressed surface CD14 and CD64 antigens. A diagnosis of rare monocytic crisis of CML was made. He was treated with low-dose nilotinib following cytoreduction with MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy. Severe leucopenia without circulating leukemic cells continued for about 2 months with sustained hepatosplenomegaly, and he died of pneumonia in March 2012. Necropsy showed severe bone marrow hypoplasia with focal infiltration of mature leukemic cells and similar infiltration in the liver.

We encountered a rare case of cytotoxic molecule-positive and Epstein-Barr virus (EBV)-associated peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which was clinically preceded by polymyositis. A 50-year-old woman with a 4-year history of steroid-refractory polymyositis developed ulcerative skin swelling on her left arm. A diagnosis of cytotoxic molecule (TIA-1)-positive and EBV-associated PTCL-NOS was made on the basis of immunohistochemical and molecular examinations of the biopsied brachial muscle. Combination chemotherapies were ineffective, with a fatal outcome. Reassessment of the biopsy specimens of the muscle taken at the age of 46 years showed that the PTCL was already present, indicating that the polymyositis was likely a paraneoplastic manifestation.

A 49-year-old man was diagnosed with pure red cell aplasia (PRCA) based on low reticulocyte count (0.1%) and near absence of erythroblasts in the bone marrow (BM). While a small number of CD20-positive large abnormal cells was observed in the BM, Multiplex PCR confirmed B cell monoclonality. Gallium scintigraphy showed abnormality only in the BM, and we made a diagnosis of PRCA secondary to BM-derived B-cell malignant lymphoma. He was treated with rituximab-combined CHOP therapy with subsequent resolution of both disorders. He was further treated with high dose chemotherapy with auto-PBSCT, sustaining complete remission of the PRCA and lymphoma.

Objective While unexplained liver dysfunction is common, it is sometimes difficult to identify its exact cause. One cause is viral infections. The identification of viruses other than hepatitis B and C that cause liver dysfunction is difficult because no methods to simultaneously identify these viruses have been established. The aim of this study was to quickly and simultaneously identify multiple virus species. Methods A total of 49 patients with unexplained liver dysfunction and undetermined inflammation were examined. The majority of patients had hematologic malignancies, and some had undergone bone marrow transplantation. Qualitative polymerase chain reactions (PCR) were performed to detect 12 species of DNA virus in whole blood. Quantitative real-time PCR was performed when a specific virus was amplified. In addition, 6 RNA hepatitis viruses were directly assayed by real-time PCR. These 2 PCR steps were completed within 1 hour. Results The most frequently detected virus in 37 patients with liver dysfunction, was transfusion transmitted virus (38%), which was followed by human herpes virus (HHV) type 6 (35%), Epstein-Barr virus (14%), cytomegalovirus (8%), and rarely hepatitis G virus and HHV-7 (3%). Similar viremia was observed in 12 patients with mild liver dysfunction. The results of the PCR assay were mostly consistent with those of routine virus serological tests. Conclusion A multiplex viral PCR assay was a useful tool for quickly identifying viruses that possibly cause liver dysfunction. It was also important that liver dysfunction acted as a proband that led to the discovery of serious viremia.

A 68-year-old female with palmoplantar pustulosis was referred to our hospital in July, 2009 because of liver dysfunction, a positive test for HTLV-1, and circulating abnormal lymphocytes with irregularly shaped nuclei. A diagnosis of acute type adult T cell leukemia/lymphoma (ATLL) was made based on generalized lymph node swelling and high levels of serum LDH, in addition to the findings described above. The associated palmoplantar pustulosis responded to some extent to antibiotics, steroid ointment, and narrow band UBV light irradiation. For ATLL, she was serially treated with CHOP chemotherapy, an LSG 15 protocol, and CytaBOM protocol with consequent partial remission. These chemotherapies did not affect the palmoplantar pustulosis. For ATLL in partial remission, we performed allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from a related donor (HTLV-1-negative) with a conditioning regimen consisting of fludarabine, melphalan, and total body irradiation with 3 Gy in February, 2010. After the engraftment of donor hematopoietic cells, ATLL cells disappeared and the patient currently (as of April, 2012) remains in complete remission (CR). The residual palmoplantar pustulosis was further improved soon after allo-PBSCT and disappeared on Day 84 after transplantation. This refractory skin disease has also been in CR to date.