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Abstract: The susceptibility of poly(ADP-ribose) polymerase-1 (Parp-1) knockout mice to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced liver carcinogenesis was analyzed. Twelve-week-old male Parp-1 +/+, Parp-1 +/− and Parp-1 −/− mice of the C57BL/6 congenic strain were fed a diet containing IQ at a concentration of 300ppm or a control diet for 60 weeks. Hepatocellular carcinomas were observed only in 1/19, 2/18 and 1/17 of the Parp-1 −/−, Parp-1 +/− and Parp-1 +/+ mice, respectively. Parp-1 deficiency did not affect the susceptibility of mice to carcinogenicity of IQ, which produces bulky DNA adducts that are repaired mainly through the nucleotide excision repair pathway. This result is in sharp contrast to the increased susceptibility of Parp-1 −/− mice to carcinogenesis induced by alkylating agents that produce DNA damage repaired mainly through base excision repair and DNA strand break repair pathways. [Copyright &y& Elsevier]

Abstract: To understand the wear mechanism of amorphous carbon nitride coatings (a-CN x ) sliding against SiC ball in water, the influence of tribological variables such as normal load (W) and sliding speed (V) on the friction coefficients (μ) and the specific wear rates (w s) was studied. The worn surfaces on disks and balls were observed by optical microscope (OM). The results indicate that the influence of the sliding speeds on the friction coefficients and the specific wear rates was more obvious than that of the normal loads. The friction coefficients and the specific wear rates decreased with an increase in the sliding speed, whereas with an increase in the normal loads, the friction coefficients and the specific wear rates fluctuated slightly. The specific wear rate of the a-CN x coatings was ten times larger than that of the SiC balls. When the sliding velocity was larger than 0.1 m/s, the friction coefficient of the a-CN x /SiC ball tribo-pair in water lubrication was smaller than 0.05 and the specific wear rates of the a-CN x coatings and the SiC balls all were at a lowest level of 10−8 and 10−9 mm3/Nm. Furthermore, the specific wear rates of a-CN x coatings and SiC balls increased linearly with friction coefficient (μ), while decreased linearly with the friction heat per unit time (μWV). To describe the friction and wear property of the a-CN x coatings sliding against SiC balls in water at the normal loads of 3∼15 N and the sliding speeds of 0.05∼0.5 m/s, the wear-mechanism map for the a-CN x /SiC tribo-pair in water was developed. [Copyright &y& Elsevier]

Abstract: Amorphous carbon-based coatings such as a-C, a-CN x and BCN coatings were deposited on SiC disks using ion beam assisted deposition (IBAD). The friction and wear property of these three carbon-based coatings against SiC balls were evaluated using a ball-on-disk tribo-meter in distilled water. The lowest mean steady-state friction coefficient of 0.015 was obtained for the a-CN x /SiC tribo-pair, while the largest mean steady-state friction coefficient of 0.09 was obtained for the a-BCN/SiC tribo-pair. Furthermore, BCN coating and SiC ball in a-BCN/SiC tribo-pair exhibited the largest specific wear rates, whereas the SiC ball had the lowest wear rate as sliding against a-CN x coatings. This indicated that the alloy elements such as N and B have different influences on the stability of the coatings in water, and thus affected the tribological property of carbon-based coatings in water. [Copyright &y& Elsevier]

Abstract: Boron carbon nitride (BCN) coatings were deposited on Si(100) wafers and Si3N4 disks by using ion beam assisted deposition from a boron carbide target. The BCN coatings were synthesized by the reaction between boron and carbon vapor as well as nitrogen ion simultaneously. The influence of deposition parameters such as ion acceleration voltage, ion acceleration current density and deposition ratio on the surface roughness and mechanical properties of the BCN coatings was investigated. The surface roughness was determined by using atomic force microscopy and the mechanical properties of the BCN coatings were evaluated by nano-indentation tests and friction tests in N2 gas. The composition and chemical bonding of the BCN coatings were analyzed by using X-ray photoelectron spectroscopy. The results showed that the lower deposition rate, the smaller surface roughness and higher nano-hardness the BCN coatings were. The BCN coating with the smoothest surface (R a = 0.25 nm and R P–V =2.8 nm) and the highest nanohardness of 33 GPa as well as excellent friction property were obtained at 0.5 nm/s and the nitrogen ions were generated at 2.0 kV and 60 μA/cm2, and the chemical composition of this BCN coating was 49 at.% B, 42 at.% C and 9 at.% N. Moreover, there were several bonding states such as B–N, B–C and C–N with B–C–N hybridization in this BCN coating. [Copyright &y& Elsevier]

Abstract: The amorphous carbon nitride coatings (a-CN x ) were deposited on Si3N4 disks using ion beam assisted deposition (IBAD), and their composition and chemical bonding were determined by X-ray photoelectron spectroscopy (XPS). The a-CN x coatings'' hardness was measured by nano-indentation and the friction and wear property of the a-CN x coatings sliding against Si3N4, SiC, Al2O3, SUS440C and SUJ2 balls in water were investigated by using ball-on-disk tribo-meter. The worn surfaces were observed using optical microscopy and analyzed by XPS. The results of XPS analysis showed that the a-CN x coatings contained 12 at.% nitrogen and the major chemical bonding was sp2 C=N and sp3C–N. The nano-hardness of the a-CN x coatings was 29 GPa, higher than those of balls. Among five kinds of tribo-systems, the lowest friction coefficient was obtained in the range of 0.01 to 0.02 for the tribo-systems with SiC and Si3N4 balls, the largest wear rate of the a-CN x coating of 1.77×10−7 mm3/Nm was obtained as sliding against Al2O3 ball, while the smallest wear rate of a-CN x coating of 1.44×10−8 mm3/Nm was gotten as sliding against Si3N4 ball. However, SUJ2 ball showed the highest wear rate of 7.0×10−7 mm3/Nm, whereas Al2O3 ball exhibited the lowest wear rate of ball of 3.55×10−9 mm3/Nm. The XPS analysis on the worn surface for the a-CN x coatings displayed that the nitrogen concentration decreased and the sp2-bonding-rich structure was formed after sliding tests in water. [Copyright &y& Elsevier]

Softening-associated changes in a cold-water-soluble pectin, CWP3 of Japanese persimmon fruit are investigated by methylation analysis. Methylation analysis showed that rhamnose occurred as (1 → 2)- and (1 → 2,4)-linked residues in CWP3 (from fresh persimmon), newly solubilized CWP3 (fraction ‘a’ from sun-dried persimmon) and depolymerized CWP3 (fraction ‘b’ from sun-dried persimmon) as expected for the presence of ‘hairy’ regions. Solubilization of pectin into CWP3 occurred with higher proportions of (1 → 5)-linked arabinan side-chains and lower proportions of (1 → 3)/(1 → 6)-linked arabinogalactan side-chains compared to the respective side chains in CWP3 (fresh persimmon). During the sun-drying process, marked losses of (1 → 3,6)-linked galactose residues from CWP3 occurred, due to extensive degradation of main-chains of arabinogalactans. This implied losses of both types of sugars, arabinose (as terminal) and galactose from arabinogalactans in CWP3 of Japanese persimmon. During the sun-drying process, the molecular size distribution of CWP3 was affected due to degradation of arabinogalactan and arabinan side-chains. [Copyright &y& Elsevier]

Antioxidative compounds were isolated from the methanol extract of fresh rhizome of smaller galanga (Alpinia officinarum Hance). Seven phenylpropanoids (1–7) were obtained and their structures were elucidated by MS and NMR analyses. They comprised the two known compounds, (E)-p-coumaryl alcohol γ-O-methyl ether (1) and (E)-p-coumaryl alcohol (6); and the five novel compounds, stereoisomers of (4E)-1,5-bis(4-hydroxy-phenyl)-1-methoxy-2-(methoxymethyl)-4-pentene (2a and 2b), stereoisomers of (4E)-1,5-bis(4-hydroxyphenyl)-1-ethoxy-2-(methoxymethyl)-4-pentene (3a and 3b), (4E)-1,5-bis(4-hydroxy-phenyl)-1-[(2E)-3-(4-acetoxyphenyl)-2-propenoxy]-2-(methoxymethyl)-4-pentene (4), (4E)-1,5-bis(4-hydroxyphenyl)-2-(methoxymethyl)-4-penten-1-ol (5), and (4E)-1,5-bis(4-hydroxyphenyl)-2-(hydroxymethyl)-4-penten-1-ol (7). Compounds 1–7 were detected for the first time as constituents of galanga rhizomes and exhibited antioxidative activities against the autoxidation of methyl linoleate in bulk phase. [ABSTRACT FROM AUTHOR]

This is the second paper of a two-part report. In the first paper, empirical data on the wear particle generation in carbon nitride coatings subjected to repeated sliding contact with a spherical diamond counter-face is reported. The effect of coating thickness on the wear particle generation is also discussed in the first paper. In this paper, a simplified theoretical expression, combining the Coffin-Manson equation with the analytical solution of a proposed elastic perfectly-plastic indentation model, is introduced. The expression successfully correlates critical number of friction cycles for wear particle generation Nc to coating thickness h, contact pressure P and radius of spherical asperity on the tip of the diamond pin R. With this expression, the lifespan of sliding components can be predicted.The theoretical results computed for diamond pin with a specific asperity radius value of 250 nm were compared with the experimental results reported in the first paper. The theoretical model successfully predicts the maximum lifespan of a component, Nc, in repeated sliding applications. The influences of various contact pressures and asperity radii on the maximum lifespan were also assessed using the model. [Copyright &y& Elsevier]

Cold-water-soluble pectic polysaccharides (CWPs) from fresh and sun-dried Japanese persimmon (Diospyros kaki) were fractionated through DEAE-cellulose (phosphate form) column and in both cases, CWPs were separated into five fractions, CWP1, CWP2, CWP3, CWP4 and CWP5. Each CWP3 was subjected to gel filtration chromatography on a Sepharose CL-6B column. Gel filtration showed that solubilization of pectin as high-molecular-weight polymer into CWP3 and depolymerization of CWP3 occurred during the sun-drying process. CWP3 (fresh persimmon) contained galactose as the predominant neutral sugar, whereas arabinose was the predominant neutral sugar in newly solubilized CWP3. A low-molecular-weight fraction of CWP3 (sun-dried persimmon) represented mainly the rhamnogalacturonan backbone of ‘hairy’ regions. The molecular size distribution of CWP3 was affected due to degradation of side-chains. Loss of arabinose occurred at a slower rate than galactose from CWP3. The results imply a softening-associated modification of Japanese persimmon pectin during the sun-drying process. [Copyright &y& Elsevier]

As a source for hematopoietic stem cell transplantation (HSCT), cord blood transplantation from unrelated donors (UCBT) is now considered as an acceptable alternative to patients who need unrelated HSCT. To confirm the findings that mismatched UCBT is feasible, we discussed here the results for 477 patients with hematologic malignancies and non-malignancies who were subjected to UCBT coordinated by the Japanese Cord Blood Bank Network (JCBBN). From February 1997 to October 2001, 411 patients with malignancies and 66 with non-malignancies had UCBT through the cord blood bank in the JCBBN; 311 patients had HLA 0-1 mismatched UCBT; 165, had a 2-4 HLA mismatch. The Kaplan-Meier estimates for 3-year disease-free survival rate (DFS) were 35.2 ± 2.8% in malignant diseases, and 33.6 ± 7.2% in patients with non-malignant diseases. The HLA disparity had no effect on DFS, incidence of acute graft-versus-host disease, or engraftment. As reported previously, we also noted the importance of graft cell dose in determining survival in UCBT. Major advantages of UCBT include its rapid availability compared with unrelated donor bone marrow, and tolerance of an HLA mismatch at 2 loci, which will enable extension of the donor pool. This review outlines the latest UCBT progress, with emphasis on practical considerations in HLA-mismatched umbilical cord blood selection. [ABSTRACT FROM AUTHOR]

An overhead rigid conductor line in a tunnel is free from the fear of disconnection because the contact wire is not tensioned, and it is superior in maintenance saving. In order to introduce this in open sections, we have developed “a long-span-type overhead rigid conductor line of catenary system.” This contact line structure consists of a contact wire of no tension attached to a supporter that has a small drag coefficient suspended from the messenger wire. We have now developed a “square supporter” to make the drag smaller and have put it to various tests with support point intervals of 50 and 10 m. As the testing results show, the contact loss is 1 to 2% at 130 km/h, and this overhead rigid conductor line can collect the current with a stability equal to that of the normal catenary system. © 2000 Scripta Technica, Electr Eng Jpn, 131(1): 94–102, 2000 [ABSTRACT FROM AUTHOR]

Lysosomal storage disorders and peroxisomal disorders are rare diseases caused by the accumulation of substrates of the metabolic pathway within lysosomes and peroxisomes, respectively. Owing to the rarity of these diseases, the prevalence of lysosomal storage disorders and peroxisomal disorders in Japan is unknown. Therefore, we conducted a nationwide survey to estimate the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. A nationwide survey was conducted following the "Manual of nationwide epidemiological survey for understanding patient number and clinical epidemiology of rare diseases (3rd version)". A questionnaire asking for detailed information, such as disease phenotypes and medical history, was created and sent to 504 institutions with doctors who have experience in treating patients with lysosomal storage disorders and peroxisomal disorders. Result A total of 303 completed questionnaires were collected from 504 institutions (response rate: 60.1%). The number of patients was estimated by calculating the rate/frequency of overlap. The estimated number of patients was 1658 (±264.8) for Fabry disease, 72 (±11.3) for mucopolysaccharidosis I, 275 (±49.9) for mucopolysaccharidosis II, 211 (±31.3) for Gaucher disease, 124 (±25.8) for Pompe disease, 83 (±44.3) for metachromatic leukodystrophy, 57 (±9.4) for Niemann-Pick type C, and 262 (±42.3) for adrenoleukodystrophy. In addition the birth prevalence was calculated using the estimated number of patients and birth year data for each disease, and was 1.25 for Fabry disease, 0.09 for mucopolysaccharidosis I, 0.38 for mucopolysaccharidosis II, 0.19 for Gaucher disease, 0.14 for Pompe disease, 0.16 for metachromatic leukodystrophy, 0.16 for Niemann-Pick type C, and 0.20 for adrenoleukodystrophy. Among the diseases analyzed, the disease with the highest prevalence was Fabry disease, followed by mucopolysaccharidosis II, adrenoleukodystrophy, Gaucher disease and metachromatic leukodystrophy. In particular, the high prevalence of mucopolysaccharidosis II and Gaucher disease type II was a feature characteristic of Japan. We estimated the number of patients with lysosomal storage disorders and peroxisomal disorders in Japan. The details of the age at diagnosis and treatment methods for each disease were clarified, and will be useful for the early diagnosis of these patients and to provide appropriate treatments. Furthermore, our results suggest that supportive care and the development of an environment that can provide optimal medical care is important in the future. [ABSTRACT FROM AUTHOR]

Phycobilisomes (PBSs), which are huge pigment-protein complexes displaying distinctive color variations, bind to photosystem cores for excitation-energy transfer. It is known that isolation of supercomplexes consisting of PBSs and photosystem I (PSI) or PBSs and photosystem II is challenging due to weak interactions between PBSs and the photosystem cores. In this study, we succeeded in purifying PSI-monomer-PBS and PSI-dimer-PBS supercomplexes from the cyanobacterium Anabaena sp. PCC 7120 grown under iron-deficient conditions by anion-exchange chromatography, followed by trehalose density gradient centrifugation. The absorption spectra of the two types of supercomplexes showed apparent bands originating from PBSs, and their fluorescence-emission spectra exhibited characteristic peaks of PBSs. Two-dimensional blue-native (BN)/SDS-PAGE of the two samples showed a band of CpcL, which is a linker protein of PBS, in addition to PsaA/B. Since interactions of PBSs with PSI are easily dissociated during BN-PAGE using thylakoids from this cyanobacterium grown under iron-replete conditions, it is suggested that iron deficiency for Anabaena induces tight association of CpcL with PSI, resulting in the formation of PSI-monomer-PBS and PSI-dimer-PBS supercomplexes. Based on these findings, we discuss interactions of PBSs with PSI in Anabaena. • PSI-PBS supercomplexes were purified from Anabaena grown under iron-deficient conditions. • CpcL, a linker protein of PBS, is bound to PSI monomers and dimers. • Iron deficiency may induce tight association of CpcL with PSI. [ABSTRACT FROM AUTHOR]

Retransplantation is the only curative treatment option for patients with acute lymphoblastic leukemia (ALL) that has relapsed after allogeneic hematopoietic cell transplantation (allo-HCT); however, data in this setting remain scant. Hence, this multicenter, retrospective study aims to determine outcome predictors after retransplantation in relapsed ALL. We examined 55 recipients who underwent multiple allo-HCTs during 2006–2018. The 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality rates were 35.9%, 29.1%, and 23.6%, respectively. We observed a trend of better outcome in Ph + ALL (n = 22) patients compared with non-Ph ALL (n = 33) patients; the 2-year PFS was 40.9% versus 21.2%, indicating a beneficial effect of more potent second- or third-generation tyrosine kinase inhibitors. Univariate analysis revealed that late relapse after the previous transplant was the only significant predictor of better transplant outcome among Ph + ALL patients, whereas factors related to prolonged OS/PFS in non-Ph ALL patients were late relapse after the previous transplant, longer duration from disease relapse/progression to second or more allo-HCT, disease status at the transplantation, and good performance status. Nevertheless, further investigations are warranted to determine whether novel molecular-targeted agents with higher efficacy and fewer toxicities could exceed conventional chemotherapies as a bridging strategy to next allo-HCT and improve the outcomes of non-Ph ALL patients. [ABSTRACT FROM AUTHOR]

Schizophyllum commune , a basidiomycete fungus, is a quite rare cause of invasive sinusitis for which no standard treatment has yet been established. We report herein a 59-year-old woman who developed S. commune rhinosinusitis after remission induction chemotherapy for her acute myeloid leukemia. No causative microorganisms were identified in the sinus lavage fluid culture, whereas nucleotide sequencing of the internal transcribed spacer region using endoscopic sinus biopsy specimen could confirm the pathogen as S. commune. Liposomal amphotericin B and voriconazole (VRCZ) treatment ameliorated both her clinical symptoms and laboratory findings. The patient was successfully treated with allogeneic stem cell transplantation, under continuous VRCZ administration, without aggravation of S. commune sinusitis. Molecular diagnosis and prompt intervention with suitable antifungal drugs may be crucial to manage this rare infectious complication. [ABSTRACT FROM AUTHOR]

• Hematopoietic cell transplantation is the only curative therapy for juvenile myelomonocytic leukemia. • Busulfan/fludarabine/melphalan seems to offer the best chance of long-term survival. • Chronic graft-versus-host disease correlates with improved survival by reducing relapse. • Treatment strategies enhancing graft-versus-leukemia effects may further improve outcome. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for juvenile myelomonocytic leukemia (JMML), but few large studies of HSCT for JMML exist. Using data from the Japan Society for Hematopoietic Cell Transplantation registry, we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011. The 5-year overall survival (OS) rate and cumulative incidence of relapse were 64% and 34%, respectively. A regimen of busulfan/fludarabine/melphalan was the most commonly used (59 patients) and provided the best outcomes; the 5-year OS rate reached 73%, and the cumulative incidences of relapse and transplantation-related mortality were 26% and 9%, respectively. In contrast, the use of the irradiation-based myeloablative regimen was the most significant risk factor for OS (hazard ratio [HR], 2.92; P =.004) in the multivariate model. In addition, chronic graft-versus-host disease (GVHD) was strongly associated with lower relapse (HR, 0.37; P =.029) and favorable survival (HR, 0.22; P =.006). The current study has shown that a significant proportion of children with JMML can be cured with HSCT, especially those receiving the busulfan/fludarabine/melphalan regimen. Based on the lower relapse and better survival observed in patients with chronic GVHD, additional treatment strategies that focus on enhancing graft-versus-leukemia effects may further improve survival. [ABSTRACT FROM AUTHOR]

• We assessed the effect of donor human T cell leukemia virus 1 serostatus on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HCT) in adult T cell leukemia-lymphoma. • There was no significant difference in overall survival or incidence of mortality. • This might aid the choice of appropriate and timely alternative donors for allo-HCT. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P =.61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P =.80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P =.66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P =.91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P =.66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed. [ABSTRACT FROM AUTHOR]

Plant tyrosine decarboxylase (TyrDC) is a group II pyridoxal 5′-phosphate (PLP)-dependent decarboxylase that mainly catalyzes the decarboxylation of tyrosine to tyramine. This is biologically important for diverting essential primary metabolites into secondary metabolic pathways. Intensive studies have characterized the effective of PLP-binding and the substrate specificity of mammalian 3,4-dihydroxyphenyl- l -alanine (Dopa) decarboxylases, a member of group II PLP-dependent decarboxylase. However, the characteristics of PLP binding and substrate specificity of plant TyrDCs remain unknown. In this study, we focus on the PLP binding manner, and determined the crystal structures of the apo and PLP binding form of type II TyrDC from Papaver somniferum (Ps TyrDCII and Ps TyrDCII-PLP). The structures showed that, unlike mammalian Dopa decarboxylase, the binding of PLP does not induce distinct conformational changes of Ps TyrDCII regarding the overall structure, but the PLP binding pocket displays conformational changes at Phe124, His203 and Thr262. Combining structural comparation and the obtained biochemical findings, it is demonstrated that Ps TyrDCII does not binds PLP tightly. Such characteristics of PLP binding may be required by its catalytic reaction and substrate binding. The activity of TyrDC probably regulated by the concentration of PLP in cells. Image 1 • Structures of apo and PLP-bind form of a plant TyrDC were determined. • For the first time to understand the PLP-binding characteristics of plant TyrDC. • Each DopaDC/TyrDC possesses its own PLP-binding manner. [ABSTRACT FROM AUTHOR]

• HLA-A, -B, -C, and -DRB1 allele mismatch effects were examined in 4050 cases of cord blood transplants. • Overall survival (OS) deteriorated in HLA 5-allele and higher mismatch in adult cord blood transplantation (CBT). • OS deteriorated in HLA 4-allele and higher mismatch in pediatric CBT. • In adult cases, 8/8 match mitigated severe acute graft-versus-host disease (GVHD) but increased the relapse rate. • In pediatric cases, 8/8 match and 1-allele mismatch mitigated acute GVHD. The impact of allele-level HLA mismatch on outcomes of cord blood transplantation has not been well established. We retrospectively analyzed the effects of HLA allele matching at HLA-A, -B, -C, and -DRB1 in cord blood transplantation for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome. In multivariate analysis, overall survival (OS) significantly deteriorated in the 4-allele or higher mismatch in pediatric cases (hazard ratio, 1.8 for 4/8 match [reference, 6/8 match] and 2.85 for 3-1/8 match) and the 5-allele or higher mismatch in adult cases (hazard ratio, 1.23 for 3-0/8 match). Incidence of grade Ⅲ to Ⅳ acute graft-versus-host disease was low in the 8/8 match and 1-allele mismatch in pediatric cases (hazard ratio, 0.19 for 8/8 match and 0.41 for 7/8 match) and the 8/8 match in adult cases (hazard ratio, 0.41 for 8/8 match). On the other hand, a higher incidence of relapse was noted in the 8/8 match in adults (hazard ratio, 1.53). The incidence of neutrophil and platelet engraftment decreased in the 3-allele or higher mismatch in adults. In subgroup analysis of graft-versus-host disease prophylaxis in adult cases, a deteriorating effect on OS of HLA 5-allele or higher mismatch was more significant in cases with calcineurin inhibitor with methotrexate than with mycophenolate mofetil. These results suggest that allele-level HLA mismatch affects the outcomes of cord blood transplantation. Information on HLA allele matching at HLA-A, -B, -C, and -DRB1 may be useful for cord blood unit selection. [ABSTRACT FROM AUTHOR]

Glecaprevir (GLE)/pibrentasvir (PIB) 300 mg/120 mg once daily (Mavyret/Maviret) is an all‐oral, pangenotypic, interferon‐ and ribavirin‐free combination regimen approved for the treatment of chronic hepatitis C virus (HCV) infection. The objective of the current analyses was to characterize the pharmacokinetics (PK) of GLE/PIB in HCV‐infected Japanese patients. Data from 332 subjects enrolled in 2 Japan phase 3 trials, CERTAIN‐1 and CERTAIN‐2, were used in the analyses. Pharmacokinetics of GLE/PIB were characterized using a nonlinear mixed‐effects modeling. The analyses evaluated the impact of covariates (concomitant medications and demographic and clinical covariates such as renal impairment, effect of cirrhotic status) on GLE/PIB PK. GLE and PIB PK were described by 1‐ and 2‐compartment models, respectively. Presence of cirrhosis, age, and body weight were identified as significant covariates on GLE/PIB PK. A trend toward higher GLE and PIB exposures in older patients and higher PIB exposures in heavier patients was observed; however, these increases were not considered clinically meaningful. GLE and PIB exposures were higher in HCV‐infected subjects with cirrhosis (Child‐Pugh A; GLE area under the plasma concentration–time curve was 160% higher, and PIB area under the plasma concentration–time curve was 21% higher) compared to subjects without cirrhosis. Renal function (including subjects with end‐stage renal disease with dialysis) had no impact on GLE or PIB exposures. The GLE/PIB dose was well tolerated in the Japanese population, and no dose adjustment is needed for the evaluated intrinsic and extrinsic factors. [ABSTRACT FROM AUTHOR]

Eisenia hydrolysis‐enhancing protein (EHEP), which is a novel protein that has been identified in Aplysia kurodai, protects β‐glucosidases from phlorotannin inhibition to facilitate the production of glucose from the laminarin abundant in brown algae. Hence, EHEP has attracted attention for its potential applications in producing biofuel from brown algae. In this study, EHEP was purified from the natural digestive fluid of A. kurodai and was crystallized using the sitting‐drop vapor‐diffusion method. Native and SAD (single‐wavelength anomalous diffraction) data sets were successfully collected at resolutions of 1.20 and 2.48 Å using wavelengths of 1.0 and 2.1 Å, respectively, from crystals obtained in initial screening. The crystals belonged to space group P212121 and contained one EHEP molecule in the asymmetric unit. All 20 S‐atom sites in EHEP were located and the phases were determined by the SAD method using the S atoms in the natural protein as anomalous scatterers (native‐SAD). After phase improvement, interpretable electron densities were obtained and 58% of the model was automatically built. [ABSTRACT FROM AUTHOR]

• Hematopoietic stem cell transplantation (HSCT) recipients exhibited low seropositivity for measles, rubella, mumps, and varicella zoster virus. • History of chronic graft-versus-host disease (GVHD) was associated with a high seropositivity rate for measles. • Nineteen of 32 HSCT recipients seronegative for measles became seropositive after vaccination. • Thirty percent of 20 HSCT recipients seronegative for rubella became seropositive after vaccination. • History of cGVHD was associated with seroconversion after vaccination. Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (n = 74), autologous HSCT (auto-HSCT) (n = 39), or chemotherapy (n = 93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients. [ABSTRACT FROM AUTHOR]

• Mortality was higher in adolescent and young adults with acute lymphoblastic leukemia (ALL) than in children with ALL. • Infection was the most common cause of treatment-related death among adolescents. • Relapse rates were similar in adolescents and young adults compared with children. • There was no difference in outcomes for older adolescents treated at pediatric centers and those treated at adult centers. Hematologic stem cell transplantation (HSCT) is the most potent consolidation therapy for high-risk acute lymphoblastic leukemia (ALL), but their outcomes and complications in adolescent and young adult (AYA) patients remain unclear. We compared outcomes after HSCT for ALL among children (age 1 to 9 years; n = 607), adolescents (age 10 to 19 years; n = 783), and young adults (age 20 to 29 years old, n = 603), based on Japanese nationwide registry data. The 5-year overall survival (OS) rate among AYA patients was worse than that of children, at 64% (95% confidence interval [CI], 60% to 68%). In the AYA, the 5-year treatment-related mortality (TRM) after HSCT was 19% (95% CI, 16% to 22%), significantly higher than that in younger patients. The most common cause of TRM in the AYA was infection. The relapse rate was not different across the 3 age groups. When focusing on older adolescents (age 15 to 19 years), there was no difference in outcomes between those treated in pediatric centers and those treated in adult centers. In conclusion, the AYA had a greater risk of nonrelapse death than younger patients, and infection was the most common cause. Further optimization is required for HSCT in AYAs with ALL. [ABSTRACT FROM AUTHOR]

The article presents case study of a 70-year-old woman cytotoxic T lymphocytes and immune deficiency in adult T cell leukemia and lymphoma. It mentions that Individuals infected with human T lymphotropic virustype 1 (HTLV-1) are susceptible to opportunistic infections with other pathogens. It presents information on precise mechanism of immune modulation in HTLV-1- positive patients.

Sodium-glucose cotransporter 1 (SGLT1) is the primary transporter for glucose absorption from digested nutrients in the gastrointestinal tract. Intestinal SGLT1 inhibition reduces post-prandial hyperglycemia and enhances the increase of plasma glucagon-like peptide-1 (GLP-1) levels. SGL5213 is a novel and potent intestinal SGLT1 inhibitor. This study characterizes the pharmacological profiles of SGL5213 in rodents. Orally administered SGL5213 was hardly absorbed and its distribution was restricted to the gastrointestinal lumen. SGL5213 significantly improved post-prandial hyperglycemia in streptozotocin (STZ)-induced diabetic rats at doses of 1 mg/kg or more. After the oral administration of starch, SGL5213 increased the amount of residual glucose in the small intestine at 1–3 h and in the cecum and colon at 3–9 h by inhibiting glucose absorption and allowing the unabsorbed glucose to be delivered into the lower-gastrointestinal tract. In the vehicle group, the plasma total GLP-1 (tGLP-1) and tGLP-2 levels increased at 15 min and the plasma total glucose-dependent insulinotropic polypeptide (tGIP) level increased at 1 h after meal loading. SGL5213 at doses of 0.1 mg/kg or more enabled the plasma levels of tGLP-1 and tGLP-2 to be retained for a period of 1–6 h, compared with the vehicle group. In contrast, SGL5213 at doses of 0.3 mg/kg or more suppressed the plasma tGIP elevation after meal loading. This study demonstrated for the first time that an intestinal SGLT1 inhibitor enhanced post-prandial plasma GLP-2 secretion. These results suggest that SGL5213 might exhibit a useful pharmacological efficacy through the physiological actions of GLP-1 and GLP-2. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) is a single-stranded RNA virus which is thought to be involved in the onset of B cell lymphoma. HCV-positive diffuse large B cell lymphoma (DLBCL) has been reported to clinically manifest in extranodal lesions (e.g., in the liver, spleen, and stomach). Here, we investigated HCV-positive and -negative primary splenic DLBCL (p-spDLBCL) and non-primary splenic DLBCL (ordinary DLBCL). Furthermore, to examine HCV lymphomagenesis, RNA in situ hybridization (ISH), RT-PCR (reverse-transcription polymerase chain reaction), and NS3 immunostaining of HCV viral nonstructural proteins were performed. HCV-positive p-spDLBCL patients presented fewer B symptoms (asymptomatic) and better performance status, with elevated presence of splenic macronodular lesions and more germinal center B cell (GCB) sub-group cases than HCV-negative p-spDLBCL patients. However, HCV-positive ordinary DLBCL patients were found to have more non-GCB sub-group cases than HCV-negative ordinary DLBCL patients. HCV-positive DLBCL patients showed 20.6% (7/34) NS3 positivity, 16.7% (1/6) HCV-RNA in situ positivity, and 22.2% (2/9) detection of HCV-RNA in tumor tissue by RT-PCR. Splenic samples were found to have a higher frequency of HCV detection than lymph node samples, thus suggesting that HCV may be closely related to lymphomagenesis, especially in splenic lymphoma. [ABSTRACT FROM AUTHOR]

The article discusses the study which identifies whether CD34-positive cells or total nucleated cells is the important method for the selection of cord blood units for haematopoietic cell transplantation. It states that cell doses should be considered when selecting cord blood units for transplantation as well as human leucocyte antigen matching.

The article informs on a phase II study conducted for evaluating whether the addition of mogamulizumab, a defucosylated humanised anti-CCR4 antibody, to mLSG15 increases efficacy in patients with newly-diagnosed aggressive adult T cell leukaemia-lymphoma (ATL). It examines its impact on allogeneic haematopoietic stem cell transplantation; and no differences were found in the survival between the mLSG15+mogamulizumab and mLSG15 arms in patients with newly diagnosed aggressive ATL.

Highlights • Bloodstream infection was documented in 13.6% of allogeneic transplant recipients. • Enteric bacteria/fungi were major (58%) causes of this infectious complication. • Bloodstream infection correlated with gastrointestinal graft-versus-host disease. • Patients with bloodstream infection showed an inferior prognosis. Abstract Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the postengraftment period (PE-BSI) after allo-HSCT. Forty-three of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: Gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accounted for 54.8%, 35.5%, and 9.7% of the isolates. Multivariate analysis revealed methylprednisolone use for graft-versus-host disease (GVHD) prophylaxis (odds ratio [OR], 6.49; 95% confidence interval [CI], 1.49 to 28.2; P =.013) and acute gastrointestinal GVHD (GI-GVHD) (OR, 8.82; 95% CI, 3.99 to 19.5; P <.0001) as risk factors for developing PE-BSI. This finding suggested that GI-GVHD increases the risk of bacterial translocation and subsequent septicemia. Moreover, among patients with GI-GVHD, insufficient response to corticosteroids, presumably related to an intestinal dysbiosis, significantly correlated with this complication. Patients with PE-BSI presented worse outcome compared with those without (3-year overall survival, 47.0% versus 18.6%; P <.001). Close microbiologic monitoring for BSIs and minimizing intestinal dysbiosis may be crucial to break the vicious cycle between GI-GVHD and bacteremia and to improve transplant outcomes especially in patients who require additional immunosuppressants. [ABSTRACT FROM AUTHOR]

The article discusses a study focusing on paediatric B-cell precursor acute lymphoblastic leukaemia (B-ALL) and clinical significance of adaptor protein SH2B3 (LNK) expression in it. Topics discussed include the determination of SH2B3 mRNA expression level in the study; the frequency of IKZF1 deletion in the patients under study; and the rate of event-free survival (EFS) in patients under study.

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 10 4 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P  < .001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P  = .14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P  = .96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P  = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD. [ABSTRACT FROM AUTHOR]

Background: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1).Methods: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12).Results: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis.Conclusions: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan. [ABSTRACT FROM AUTHOR]

Background: The once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan.Methods: CERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks. The primary efficacy endpoint was non-inferiority of G/P compared to OBV/PTV/r by assessing SVR at post-treatment week 12 (SVR12) among non-cirrhotic patients without the NS5A Y93H polymorphism.Results: SVR12 was achieved by 128/129 (99.2%; one patient lost to follow-up) non-cirrhotic patients in the 8-week G/P Arm (including 23/23 patients with the NS5A Y93H polymorphism) and 52/52 (100%) patients in the 12-week OBV/PTV/r Arm. No patients from the G/P Arm prematurely discontinued the study drug or experienced a treatment-emergent serious adverse event (TESAE). Three patients from the OBV/PTV/r Arm experienced five TESAEs and one of these patients discontinued the study drug due to TESAEs. All 38 (100%) patients with compensated cirrhosis achieved SVR12; in this group, no TESAEs were reported and one patient discontinued treatment due to an AE.Conclusions: CERTAIN-1 study results demonstrate high efficacy and favorable tolerability of G/P in GT1-infected Japanese patients including those with the NS5A Y93H polymorphism, with no virologic failures observed. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P  = .008), U-CB (HR, 3.80; 95% CI, 2.07 to 6.95; P  < .001), or HLA-mismatched related donor grafts (HR, 6.18; 95% CI, 2.70 to 14.15; P  < .001). Mortality after the relapse or progression of CMML did not significantly differ among the 4 types of donor source. Transplantation-related mortality was highest in recipients of U-CB (HR, 3.32; 95% CI, 1.33 to 8.26; P  = .010). In patients with CMML, allo-HSCT using an alternative donor may contribute to durable remission; however, further improvements in transplantation-related mortality are required for this type of transplantation. [ABSTRACT FROM AUTHOR]

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense . In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil–based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P  = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P  = .05) and better 4-year OS (55.6% versus 20%; P  = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. [ABSTRACT FROM AUTHOR]

Few reports have focused on adolescent and young adult (AYA) patients with acute myeloid leukemia (AML) treated with hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis based on data obtained from a Japanese nationwide registration database to compare HSCT outcomes in AYA patients with AML with those in children with AML. An analysis of the 2973 patients with de novo AML who received allogeneic HSCT from 1990 to 2013 showed inferior 5-year overall survival (OS) (54% versus 58%, P  <   .01) and increased treatment-related mortality (TRM) (16% versus 13%, P  = .02) in AYA patients. Multivariate analysis for both OS and TRM showed a significant negative impact on AYAs. However, the negative impact of older age lost its significance in an additional analysis focusing on 1407 recent transplant recipients with high-resolution HLA typing (2000 to 2013). Finally, we analyzed the impact of transplantation center type on HSCT outcomes in 317 adolescent patients (15 to 18 years old) and found no difference in outcomes between patients treated at a pediatric or an adult hospital. Higher age was a strong predictive factor for inferior OS resulting from increased TRM, which can be eliminated with better donor selection using high-resolution HLA typing. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib ( n = 37), nilotinib ( n = 30) or dasatinib ( n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment. [ABSTRACT FROM AUTHOR]

Objectives T-cell prolymphocytic leukemia (T- PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified ( PTCL- NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T- PLL and PTCL- NOS. Methods We analyzed 15 T- PLL and 91 PTCL- NOS patients and also compared clinical features between T- PLL and PTCL- NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. Results T-PLL cells were smaller in size than those of PTCL- NOS with leukemic presentation ( P=.0068); moreover, PTCL- NOS cells with leukemic presentation were smaller than those of PTCL- NOS without leukemic presentation ( P=.0017). Immunophenotypic patterns in T- PLL and PTCL- NOS were similar. Five-year overall survival rates of T- PLL and all PTCL- NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T- PLL and PTCL- NOS with leukemic presentation had essentially equivalent characteristics. Conclusion T-PLL and PTCL- NOS may share common biological and clinical characteristics in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Anthracyclines are used to treat childhood acute lymphoblastic leukemia (ALL). Even when administered at low doses, these agents are reported to cause progressive cardiac dysfunction. We conducted a clinical trial comparing the toxicities of two anthracyclines, pirarubicin (THP) and daunorubicin (DNR), in the treatment of childhood ALL. The results from our study that relate to acute and late toxicities are reported here. Methods: 276 children with B-ALL were enrolled in the trial from April 1997 to March 2002 and were randomly assigned to receive a regimen including either THP (25 mg/m × 11) or DNR (30 mg/m × 11). Acute toxicity was prospectively assessed based on the National Cancer Institute Common Toxicity Criteria. Acute hematological toxicity was also examined via some parameters. Patients with event-free survival of >5 years were retrospectively surveyed for cardiac function at 5 and 10 years and at the most recent assessment more than 10 years from the onset of ALL. Results: Acute hematological toxicity in the early phase was more significant in the THP arm. Based on ultrasound cardiography, cardiac function was impaired in both groups during the follow-up period, but there was no significant difference between the groups except for a greater decline in fractional shortening on ultrasound cardiography in the DNR arm. Conclusions: While acute hematological toxicity was more significant in the THP arm, THP also appeared to be less cardiotoxic. However, the evaluation of late cardiotoxicity was limited because only a few subjects were followed beyond 10 years after ALL onset. Considering that the THP regimen produced an EFS rate comparable with that of the DNR regimen, the efficacy and toxicity of THP at reduced doses should be studied in order to identify potentially safer regimens. [ABSTRACT FROM AUTHOR]

Background A nationwide, multicenter and observational study was retrospectively conducted to evaluate the clinical utility of Cepharanthin ( CEP) for pediatric patients with chronic immune thrombocytopenia ( ITP). Methods Clinical and laboratory data for 46 Japanese patients aged <16 years who were diagnosed as having chronic ITP in 14 hospitals during 2001-2011, and were treated with CEP for >12 months, were analyzed. Results Median daily CEP dose was 1 mg/kg (range, 0.12-2 mg/kg). Median platelet count prior to CEP was 20.5 × 109/L ( IQR, 8.3-53.0 × 109/L), and then significantly increased to 58.5 × 109/L ( IQR, 22.8-115.0 × 109/L) and 69.0 × 109/L ( IQR, 23.0-134.0 × 109/L) at 12 and 24 months of treatment, respectively. No life-threatening bleeds or moderate-severe adverse events were reported. Of 38 patients who received both corticosteroids ( CS) and CEP, 17 patients (45%) were weaned from CS, and 15 patients (39%) attained the reduced dose of CS. The duration from the start of CEP to the stopping of CS was a median of 413 days (range, 49-1734 days) in patients who were weaned from CS. Conclusions CEP alone or combined with CS was useful for the management of pediatric chronic ITPs. [ABSTRACT FROM AUTHOR]

We assessed the clinical utility of next-generation sequencing ( NGS)-based monitoring of minimal residual disease ( MRD) in a uniformly treated cohort of 79 patients with paediatric B-cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre- (4-5 months) and post- (24 months) maintenance therapy time points, and at relapse. We identified leukaemia-specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4-5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561-21·6), P < 0·001], at 4-5 months [ RR (95% CI) = 10·24 (3·374-31·06), P < 0·001], and at 24 months [ RR (95% CI) = 19·26 (4·974-74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia-free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS- MRD for patients with B-cell ALL. [ABSTRACT FROM AUTHOR]

Background: Impaired glucose tolerance (IGT) patients are known to have a high risk of cardiovascular events and their prognosis has been reported to be poor. The present study aimed to compare coronary plaque characteristics among coronary artery disease (CAD) patients with normal glucose tolerance (NGT), those with IGT, and those with diabetes mellitus (DM) by using optical coherence tomography (OCT). Methods: The present study included 101 coronary artery disease patients (mean age, 67.9 ± 10.4 years; 82.4% male). OCT was performed for target and non-target vessels during percutaneous coronary intervention. The patients were divided into the following 3 groups: the NGT, IGT, and DM groups. Results: A total of 136 non-target residual plaques were found in 101 patients (27, 30, and 44 in the NGT, IGT, and DM groups, respectively). The size of the lipid core expressed as the mean angle of the lipid arc was significantly greater in the IGT and DM groups than in the NGT group (163.0 ± 58.7°, 170.1 ± 59.3°, and 130.9 ± 37.7°, respectively, P < 0.05). The fibrous cap covering the lipid core was significantly thinner in the IGT group than in the NGT group (77.0 ± 23.4 μm vs. 105.6 ± 47.0 μm, P = 0.040). Conclusion: The coronary plaques in CAD patients are more vulnerable when having IGT compared to those with NGT, and similar to those with DM. This finding may explain the high risk of cardiovascular events in CAD patients with IGT. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best therapeutic option for childhood high-risk acute leukemia. However, which donor source is optimal for children lacking an identical sibling remains unclear. To evaluate the clinical impact of donor source on allo-HSCT in childhood acute leukemia, we analyzed data from 577 children who underwent allo-HSCT after a myeloablative regimen during first or second complete remission from 2005 to 2012, using registry data of the Japan Society for Hematopoietic Cell Transplantation, and we compared outcomes of 7/8 to 8/8 HLA allelic–matched unrelated bone marrow transplantation (UR-BMT, n = 218) and 4/6 to 6/6 HLA allelic–matched unrelated cord blood transplantation (UR-CBT, n = 200) to those of HLA-identical related bone marrow transplantation (ID-BMT, n = 159). The median follow-up of survivors was 40.0 months. Three-year overall survival (OS) and leukemia-free survival (LFS) rates for ID-BMT, UR-BMT, and UR-CBT were 74.8% and 69.0%, 75.0% and 69.6%, and 71.8% and 63.8%, respectively. The multivariate analysis demonstrated that OS and LFS for the 3 groups are comparable, although UR-CBT carries a greater risk of nonrelapse mortality (hazard ratio, 2.20; P  = .03, compared to ID-BMT) in the myeloablative setting for childhood high-risk acute leukemia. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to assess the efficacies of the myocardial T1 value and the extracellular volume fraction (ECV) for determining the severity of myocardial fibrosis in patients with non-ischemic cardiomyopathy. Materials and methods Myocardial fibrosis is considered the most important indicator of cardiac damage associated with non-ischemic cardiomyopathy. Recently, modified Look-Locker inversion recovery imaging (MOLLI) has been used for T1 mapping and measurement of the ECV for the assessment of myocardial fibrosis. The present study included 22 patients (mean age, 61.5 ± 12.7; 21 male) with non-ischemic heart failure. Motion corrected myocardial T1 mapping was automatically performed using a MOLLI sequence, and the ECV was estimated from the pre- and post-contrast blood and myocardial T1 values corrected for the hematocrit level. All endomyocardial biopsy specimens were obtained from the inferoposterior left ventricular wall. The percentage of myocardial fibrosis (%F) was determined after Elastica Masson-Goldner staining as follows: (fibrosis area/[fibrosis area + myocardial area]) × 100. Results No correlation was noted between the %F and the pre- (r = 0.290, p = 0.191) or post-contrast T1 values (r = − 0.190, p = 0.398); however, a significant correlation was noted between the %F and ECV (r = 0.750, p < 0.001). Conclusions In this study, the ECV reflected the extent of myocardial fibrosis, but the pre- and post-contrast T1 values did not. The ECV may be used to estimate the severity of myocardial fibrosis in patients with non-ischemic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P  = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. [ABSTRACT FROM AUTHOR]