Monthly monitoring of HBV DNA is useful for preventing HBV reactivation-related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).

The linking of integrin to cytoskeleton is a critical event for an effective cell migration. Previously, we have reported that a novel integrin-linked kinase (ILK)–binding protein, affixin, is closely involved in the linkage between integrin and cytoskeleton in combination with ILK. In the present work, we demonstrated that the second calponin homology domain of affixin directly interacts with α-actinin in an ILK kinase activity–dependent manner, suggesting that integrin–ILK signaling evoked by substrate adhesion induces affixin–α-actinin interaction. The overexpression of a peptide corresponding to the α-actinin–binding site of affixin as well as the knockdown of endogenous affixin by small interference RNA resulted in the blockade of cell spreading. Time-lapse observation revealed that in both experiments cells were round with small peripheral blebs and failed to develop lamellipodia, suggesting that the ILK–affixin complex serves as an integrin-anchoring site for α-actinin and thereby mediates integrin signaling to α-actinin, which has been shown to play a critical role in actin polymerization at focal adhesions.

The muscle-related complications of fasciitis and myositis, caused by chronic GVHD after Allo-SCT are relatively rare, but at times will severely impair a patient's quality of life (QOL). We performed a retrospective analysis in Japanese Allo-SCT recipients to identify the incidence, risk factors and clinical features of fasciitis and myositis. In 1967 patients who underwent Allo-SCT between January 1994 and March 2005 and survived beyond 90 days post transplantation, eight patients developed fasciitis and nine patients developed myositis, with a 5-year cumulative incidence of 0.55% and 0.54%, respectively. The median time from SCT to the development of fasciitis and myositis was 991 and 660 days, respectively. PBSCT was a risk factor for developing fasciitis, but no risk factors were found for myositis. The response to immunosuppressive treatment was better in patients with myositis than fasciitis, and the overall survival after developing these symptoms was better in patients with myositis than those with fasciitis. An early diagnosis by a biopsy, which includes fascia and muscle or magnetic resonance imaging (MRI) and prompt treatment may be important to prevent an impairment of the patient's QOL with persistent disability.

Anaplastic thyroid cancer (ATC) is associated with an extremely poor prognosis and is resistant to the majority of chemotherapies. In 2015, lenvatinib was approved for treating ATC in Japan. The present study aimed to evaluate the overall survival (OS) of patients with ATC treated with lenvatinib. A total of 23 patients with a definitive histological diagnosis of ATC who were treated at Kanagawa Cancer Center (Yokohama, Kanagawa. Japan) were enrolled. Surgical treatment was possible in 10 patients (including one debulking surgery), and lenvatinib treatment was postoperatively started. The remaining 13 patients were not eligible for debulking surgery; thus, lenvatinib was promptly approved as a life-saving treatment. The therapeutic effect was determined according to the Response Evaluation Criteria In Solid Tumors criteria (ver.1.1). The patients exhibited a lenvatinib response rate of 17.4% and a disease control rate of 43.5%. However, lenvatinib was associated with a 100% incidence of treatment-related adverse events (AEs), with hypertension being the most common AE (91.3%). Additionally, dose interruptions and reductions were required due to the development of tumor fistulas or other tumor-related AEs, and 9 (39.1%) patients discontinued treatment due to grade 3 or higher AEs. The median OS time was 166 days. Overall, the present study demonstrated the effectiveness of lenvatinib against ATC, which is often chemotherapy-resistant. Successful treatment of fistulas developing due to tumor necrosis at the site of the primary lesion is crucial for improving the patient outcome. The response to lenvatinib in patients with ATC varies on a case-by-case basis and requires further investigation in future studies.

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We retrospectively studied the association between iron overload and bloodstream infections (BSI) in the 100-day period following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia or myelodysplastic syndromes. Serum ferritin was measured before transplantation to evaluate iron overload. Of 114 adult patients who underwent transplantation between 2000 and 2008, 36 (32%) developed BSI. Of the 44 isolates, 63% were Gram-positive bacteria, 32% were Gram-negative bacteria, and 4% were fungi. The median time to the onset of the first BSI was day 28 (range day 0-95) after transplantation. Univariate analysis revealed a significantly higher incidence of BSI in the high (≥ 1,000 ng/ml, n = 57) than in the low (< 1,000 ng/ml, n = 57) ferritin group (42.1 versus 21.1%, respectively, P = 0.017). Peripheral blood stem cell transplantation (PBSCT) (n = 23) showed a greater protective effect against BSI compared with bone marrow (n = 71) and cord blood (n = 20) transplantation. Pretransplantation serum ferritin (HR = 2.844, 95% CI: 1.180-6.859, P = 0.020) and PBSCT (HR = 0.135, 95% CI: 0.025-0.717, P = 0.019) were significant factors on multivariate analysis. In conclusion, pretransplantation serum ferritin significantly predicts BSI within the 100-day period after allo-HSCT.

Enteropathy-associated T-cell lymphoma (EATL) is a rare primary T-cell lymphoma of the digestive tract. EATL is classified as either Type I, which is frequently associated with and thought to arise from celiac disease and is primarily observed in Northern Europe, and Type II, which occurs de novo and is distributed all over the world with predominance in Asia. The pathogenesis of EATL in Asia is unknown. We aimed to clarify the histological and genomic profiles of EATL in Japan in a homogeneous series of 20 cases. The cases were characterized by immunohistochemistry, high-resolution oligonucleotide microarray, and fluorescence in situ hybridization (FISH) at five different loci: 1q21.3 (CKS1B), 6q16.3 (HACE1), 7p22.3 (MAFK), 9q33.3 (PPP6C), and 9q34.3 (ASS1, CARD9) using formalin-fixed paraffin-embedded sections. The histological appearance of EATL ranged from medium-to large-sized cells in 13 cases (65%), small-to medium-sized cells in five cases (25%), and medium-sized in two cases (10%). The immunophenotype was CD2 + (60%), CD3e + (100%), CD4 + (10%), CD7 + (95%), CD8 + (80%), CD56 + (85%), TIA-1 + (100%), Granzyme B + (25%), T-cell receptor (TCR)β + (10%), TCRγ + (35%), TCRγδ + (50%), and double negative for TCR (six cases, 30%). All cases were EBER − . The genomic profile showed recurrent copy number gains of 1q32. 3, 4p15.1, 5q34, 7q34, 8p11.23, 9q22.31, 9q33.2, 9q34.13, and 12p13.31, and losses of 7p14.1. FISH showed 15 patients (75%) with a gain of 9q34.3 with good correlation with array comparative genomic hybridization. EATL in Japan is characterized by non-monomorphic cells with a cytotoxic CD8 + CD56 + phenotype similar to EATL Type II. The genomic profile is comparable to EATL of Western countries, with more similarity to Type I (gain of 1q and 5q) rather than Type II (gain of 8q24, including MYC). The 9q34.3 gain was the most frequent change confirmed by FISH irrespective of the cell origin of αβ-T-cells and γδ-T-cells.

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