Prolonged incubation period of hepatitis B in a recipient of a nucleic acid amplification test-negative hepatitis B virus window donation.

Background: The occurrence of transfusion-transmitted hepatitis B virus (HBV) infection has fallen dramatically due to continuous improvements in pre-transfusion laboratory testing. However, the characteristics of transfusion-transmitted HBV infection caused by individual donor nucleic acid amplification test (ID-NAT)-negative blood products are unclear.

Case Presentation: A 76-year-old woman with acute myeloid leukemia was diagnosed with transfusion-transmitted HBV infection after receiving apheresis platelets derived from an ID-NAT-negative blood donation.

Primary human herpesvirus 8-negative effusion-based lymphoma: a large B-cell lymphoma with favorable prognosis.

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)-negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan.

A survey of blood transfusion errors in Aichi Prefecture in Japan: Identifying major lapses threatening the safety of transfusion recipients.

Background: Despite recent progress in blood systems, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. This study investigated the actual statuses of blood transfusion errors at institutions of all sizes in Aichi prefecture.

Materials And Methods: We investigated 104 institutions that perform 98 % of the blood transfusions in Aichi prefecture, and investigated the errors (incidents/accidents) that occurred at these facilities over 6 months (April to September, 2017).

Efficacy and safety of tyrosine kinase inhibitors for newly diagnosed chronic-phase chronic myeloid leukemia over a 5-year period: results from the Japanese registry obtained by the New TARGET system.

We report the results of a multicenter observational study using the New TARGET system, in which the effectiveness and safety of tyrosine kinase inhibitors (TKIs) were evaluated in newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients. A total of 506 patients were enrolled between April 2010 and March 2013. Median age was 56 (range 18-92) years; 35% of patients were females.

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201.

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.

Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study.

The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR).

High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG.

High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063).

Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia.

Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17).

Long-term treatment with bosutinib in a phase 1/2 study in Japanese chronic myeloid leukemia patients resistant/intolerant to prior tyrosine kinase inhibitor treatment.

This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3‒372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively.

Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation.

Although therapeutic drug monitoring based on blood concentration has been widely implemented in transplant recipients treated with immunosuppressive agents, clinical adverse events such as rejection, infection or drug-induced toxicity caused by inappropriate dosage cannot be completely controlled. Development of an effective assay for optimized immunosuppression would be desirable, which can potentially lead to personalized medicine in renal transplantation. Cyclosporine (CSA) pharmacodynamic analysis using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based T cell proliferation assay was examined in 66 kidney transplant recipients before and after transplantation.

Comparative analysis of drug action on B-cell proliferation and differentiation for mycophenolic acid, everolimus, and prednisolone.

Background: Although more attention has been paid recently to B-cell immunity, assay for B-cell analysis has yet to be clinically applicable because, unlike T cell, a B-cell culture system has not been well established.

Methods: We attempted to develop an in vitro culture system for the proliferation and differentiation of peripheral B cells into plasma cells, and to analyze the action of everolimus (EVR), mycophenolic acid (MPA), and prednisolone (PRD).

Results: Using a three-step culture system, peripheral CD19 B cells could differentiate into plasma cells and produce IgG antibody.

Interstitial fluid shifts to plasma compartment during blood donation.

Background: A vasovagal reaction (VVR) occurs in 0.8% to 0.9% of voluntary blood donors in Japan.

[May-Hegglin anomaly--from genome research to clinical laboratory].

The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS) and Fechtner syndrome (FTNS), are rare disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like cytoplasmic inclusions in granulocytes. Epstein syndrome (EPS) is another autosomal dominant macrothrombocytopenia associated with Alport syndrome but without leukocyte inclusions. We previously mapped the locus for MHA on chromosome 22q12.

Expression of low-frequency Ala108Pro substitution in the platelet glycoprotein Ibbeta gene.

We determined the gene frequency of the glycoprotein (GP) Ibbeta Ala108Pro substitution. The Pro108 allele was not found in 208 healthy Japanese and 200 healthy Caucasians. In vitro expression studies showed surface expression of the GPIbbeta Pro108 variant, suggesting the possibility of the involvement of the substitution as an alloantigen.

Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations.

The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly, Sebastian syndrome, and Fechtner syndrome, are rare human disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like cytoplasmic inclusions in granulocytes. Epstein syndrome is another autosomal dominant macrothrombocytopenia associated with Alport syndrome but without leukocyte inclusions. These disorders are caused by mutations in the same gene, the MYH9, which encodes the nonmuscle myosin heavy chain-A (NMMHCA).

Epitope analysis of antibodies in Japanese to human cytomegalovirus phosphoprotein 150 with synthetic peptides.

Serological detection of antibodies specific to human cytomegalovirus (HCMV) is not reliable because the assay uses the whole HCMV protein fraction. Antigenic materials composed of well-characterized viral proteins are being tried for serodiagnosis in Europe. Epitopes of antibodies to HCMV phosphoprotein 150 (pp150) encoded by UL32 in Japanese individuals were investigated for comparison with the results in Europe.

Novel nonsense mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome.

Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder caused by quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX, and GPV, and the coordinated assembly of GPIbalpha, GPIbbeta, and GPIX is required for the efficient surface expression of a functional complex. We report here a novel nonsense mutation of the GPIbbeta gene associated with BSS.

Novel heterozygous missense mutation in the platelet glycoprotein Ib beta gene associated with isolated giant platelet disorder.

The glycoprotein (GP) Ib/IX/V complex plays an important role in primary hemostasis, serving as the platelet receptor for von Willebrand factor (vWF). Recent studies have shown that the phenotype caused by mutations in the subunits of the GPIb/IX complex spans a wide spectrum; from the normal phenotype, to isolated giant platelet disorders (GPD), and to the full-blown bleeding disorder, the Bernard-Soulier syndrome (BSS). We characterize here a novel missense mutation of the GPIb beta gene associated with isolated GPD.

Presence of Propionibacterium acnes in blood components.

Background: Sterility testing, as part of the QC of blood components at the Japanese Red Cross Aichi Blood Center between April 1998 and March 2000, showed that 10 of 5568 tested blood components (0.18%), all of which were RBC concentrates, were contaminated with bacteria. Nine isolates were Propionibacterium acnes and one was Staphylococcus capitis.

Homozygous Pro74-->Arg mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome.

Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX and GPV. We describe here the genetic basis of the disorder in a patient with BSS.

Detailed characterization of an anti-factor IX monoclonal antibody that neutralizes the prolonged ox brain prothrombin time of hemophilia B(M) by synthetic peptides.

In a previous study, we prepared a monoclonal antibody (MoAb) to coagulation factor IX (FIX), designated 65-10, which interfered with the activation of FIX by the activated factor XI/Ca(2+) and neutralized the prolonged ox brain prothrombin time of hemophilia B(M) [11,12]. The location of the epitope on the FIX for 65-10 MoAb is (168) Ile-Thr-Gln-Ser-Thr-Gln-Ser-Phe-Asn-Asp-Phe-Thr-Arg-Val-Val(182) [21]. In this paper, we studied in more detail an epitope on FIX using the systematic substitution of different amino acids at each residue of the epitope peptides and the influence of the epitope peptide on the prolonged ox brain prothrombin time of the hemophilia B(M) plasma of 65-10 MoAb.

Mapping of a gene for May-Hegglin anomaly to chromosome 22q.

May-Hegglin anomaly (MHA) is a rare autosomal dominant platelet disorder characterized by the triad of giant platelets, thrombocytopenia and leukocyte inclusions. Both the molecular and the genetic defects responsible for this disorder remain unknown. In order to map the gene responsible for MHA, we performed a genome-wide linkage study using highly polymorphic short tandem repeat markers in a single Japanese MHA family.

Platelet glycoprotein (GP) V polymorphisms in Japanese.

The glycoprotein (GP) V is a subunit of a platelet receptor for von Willebrand factor, the GPIb/IX/V complex. Recently, polymorphisms in the GPV gene, four involving amino acid changes and five silent, were identified. We developed an allele-specific restriction method to determine the gene frequencies of the non-synonymous substitutions in Japanese and Caucasians.

Clinical evaluation of repeat apheresis donors in Japan.

Background And Objectives: To ascertain the safety of repeat apheresis donation, hematological and biochemical tests were performed on 511 donors with a donation rate of over 6 times per year for a period of 12-19 months.

Materials And Methods: Repeat donors who had apheresis more than 6 times in the previous year were chosen. Data for the repeat donors at the start of the experiments were compared with those at the end of the study.