Extracellular Vesicles Derived from the Serum of Seriola quinqueradiata Induce Human Umbilical Vein Endothelial Cell Proliferation through Angiogenic Signaling.

Daily intake of extracellular vesicles (EVs) derived from fish (f-EVs) may contribute to health maintenance by reducing cardiovascular risk. However, their physicochemical and biological properties remain unclear. In this study, we compared the physical characteristics (size, zeta potential, and free fatty acid composition) and biological characteristics (cell proliferation) of f-EVs with those of EVs derived from mammals (m-EVs). In the physical characteristic analysis, f-EVs derived from Pagrus major (PMS-EVs) and Seriola quinqueradiata (SQS-EVs) had a negatively charged and a positively charged group and higher levels of unsaturated fatty acids, unlike m-EVs. In the biological characteristic analysis for f-EVs, SQS-EV enhanced the human umbilical vein endothelial cell proliferation via vascular endothelial growth factor receptor 2, fibroblast growth factor receptor 1, or platelet-derived growth factor ß. These data suggest that SQS-EVs have unique functions compared with other EVs. To the best of our knowledge, this is the first study to show that SQS-EVs act positively on human cells.

Feasibility and usefulness of recommended screenings at long-term follow-up clinics for hematopoietic cell transplant survivors.

PURPOSE: Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic. METHODS: We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions. RESULTS: Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers. CONCLUSIONS: Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.

Efficacy and Safety of 4-Weekly Docetaxel for Castration-Resistant Prostate Cancer.

We investigated the efficacy and safety profiles of 4-weekly docetaxel for castration-resistant prostate cancer. Patients treated with ≥2 courses of docetaxel chemotherapy (median, 70 mg/m2) between 2008 and 2018 were included. Among 125 Japanese men, 40 (32.0%) and 85 (68.0%) were treated with 3-weekly and 4-weekly regimens, respectively. In the 4-weekly regimen, the risks of progression, treatment failure, and any-cause mortality were comparable to those in the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. These data suggest that the 4-weekly regimen may be an acceptable option for selected patients.

Campylobacter fetus bacteremia and meningitis in an acute lymphoblastic leukemia patient undergoing maintenance therapy: a case report.

BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Characterization of Late Acute and Chronic Graft-Versus-Host Disease according to the 2014 National Institutes of Health Consensus Criteria in Japanese Patients.

To characterize the incidences and outcomes of late acute (LA) and chronic graft-versus-host disease (GVHD) in East Asians according to the 2014 National Institutes of Health criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involved sites at the onset of LA GVHD included the skin (71%), gut (13%), and liver (8%). The cumulative incidences of relapse, nonrelapse mortality (NRM), transition to chronic GVHD, and discontinued systemic treatment were 11%, 6%, 22%, and 46%, respectively, at 48 months after onset of LA GVHD. Cox models showed that prior acute GVHD was associated with NRM, and HCT from a female donor to a male patient, myeloablative conditioning, and low Karnofsky performance status were associated with a longer duration of systemic treatment after LA GVHD. The most frequently involved sites at the onset of chronic GVHD included the mouth (83%), liver (75%), skin (69%), and eyes (62%). Cox models showed that use of antithymocyte globulin in conditioning regimens was associated with a higher risk of discontinued systemic treatment after the onset of chronic GVHD. The cumulative incidences of relapse, NRM, and discontinued systemic treatment were 16%, 11%, and 41%, respectively, at 48 months after the onset of chronic GVHD. Our results suggested several potential differences between Japanese patients and those of other ethnicities. A direct comparison is needed to formally investigate ethnic differences.

Resolved versus Active Chronic Graft-versus-Host Disease: Impact on Post-Transplantation Quality of Life.

The aim of this study was to determine whether impaired quality of life (QOL) persisted among patients who experienced resolved chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Eligible participants were patients who were relapse-free for 3 years after allo-HCT who were age ≥16 years at the time of transplantation and age ≥20 years without relapse at the time of the survey. The Medical Outcomes Study's 36-Item Short-Form Survey (SF-36), the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and a visual analog scale (VAS) were administered to assess QOL. Physicians evaluated the current status of chronic GVHD at survey using National Institutes of Health (NIH) criteria, and pretransplantation characteristics and history of GVHD were extracted from the national transplant registry database. Patients without currently active GVHD but with a history of chronic GVHD were categorized as having "resolved GVHD." Of 1250 patients informed of the study, 1216 provided consent and 1130 were included in the final analysis. A total of 745 patients (66%) had currently active chronic GVHD, 149 (13%) had resolved chronic GVHD, and 236 (21%) never had chronic GVHD after allo-HCT. Multivariable analyses showed that compared with patients with resolved or no chronic GVHD, those with active chronic GVHD reported significantly poorer QOL. The QOL scores were similar in patients with resolved chronic GVHD and those without chronic GVHD. Greater between-group differences were observed in SF-36 Physical component and VAS scores in patients age ≥50 years, but the differences were not statistically significant. Our data indicate that only currently active chronic GVHD has a significant impact on physical, mental, and social QOL in allo-HCT survivors, whereas previous chronic GVHD does not impair QOL if it has been resolved.

Quality of Life after Allogeneic Hematopoietic Cell Transplantation According to Affected Organ and Severity of Chronic Graft-versus-Host Disease.

Knowing the impact of chronic graft-versus-host disease (GVHD) on quality of life (QoL) after allogeneic hematopoietic stem cell transplantation (allo-HCT) by GVHD type and severity is critical for providing care to transplant survivors. We conducted a cross-sectional questionnaire study to examine the relationship between patient-reported QoL as measured by the Medical Outcomes Study 36-Item Short-Form Health Survey, Functional Assessment of Cancer Therapy-Bone Marrow Transplant, and visual analogue scale (VAS) and chronic GVHD defined by the National Institutes of Health (NIH) criteria. Recipients of allo-HCT for hematologic disease between 1995 and 2009 aged ≥ 16 years at transplant and ≥20 years at the time of the survey who were relapse-free were eligible. A total of 1140 pairs of patient and physician questionnaires were included in the analysis. By NIH global severity score, QoL scores in all aspects were significantly lower in patients with higher global and organ-specific severity grades, independent of background variables. Compared with patients without GVHD symptoms, those with mild symptoms had impaired physical and general QoL according to global severity score and organ-specific scores except for the genital tract. Mild symptoms in the lungs, gastrointestinal tract, and joints and fascia were associated with clinically meaningful deterioration of physical QoL. VAS scores provided by physicians were generally higher than those provided by patients. Differences between scores reported by patients and physicians were larger for patients with no or mild GVHD symptoms. Our findings based on more than 1000 long-term survivors after HCT enabled us to identify a target of care, informing survivorship care protocols to improve post-transplantation QoL.

Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia harboring trisomy 8.

Trisomy 8 (+8) is one of the most common cytogenetic abnormalities in adult patients with acute myeloid leukemia (AML). However, the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with AML harboring +8 remains unclear. To evaluate, the outcome and prognostic factors in patients with AML harboring +8 as the only chromosomal abnormality or in association with other abnormalities, we retrospectively analyzed the Japanese registration data of 631 adult patients with AML harboring +8 treated with allogeneic HSCT between 1990 and 2013. In total, 388 (61%) patients were not in remission at the time of HSCT. With a median follow-up of 38.5 months, the probability of overall survival and the cumulative incidence of relapse at 3 years were 40 and 34%, respectively. In the multivariate analysis, two or more additional cytogenetic abnormalities and not being in remission at the time of HSCT were significantly associated with a higher overall mortality and relapse. Nevertheless, no significant impact on the outcome was observed in cases with one cytogenetic abnormality in addition to +8. Although more than 60% of the patients received HSCT when not in remission, allogeneic HSCT offered a curative option for adult patients with AML harboring +8.

Field-induced superconducting phase of FeSe in the BCS-BEC cross-over.

Fermi systems in the cross-over regime between weakly coupled Bardeen-Cooper-Schrieffer (BCS) and strongly coupled Bose-Einstein-condensate (BEC) limits are among the most fascinating objects to study the behavior of an assembly of strongly interacting particles. The physics of this cross-over has been of considerable interest both in the fields of condensed matter and ultracold atoms. One of the most challenging issues in this regime is the effect of large spin imbalance on a Fermi system under magnetic fields. Although several exotic physical properties have been predicted theoretically, the experimental realization of such an unusual superconducting state has not been achieved so far. Here we show that pure single crystals of superconducting FeSe offer the possibility to enter the previously unexplored realm where the three energies, Fermi energy εF, superconducting gap Δ, and Zeeman energy, become comparable. Through the superfluid response, transport, thermoelectric response, and spectroscopic-imaging scanning tunneling microscopy, we demonstrate that εF of FeSe is extremely small, with the ratio Δ/εF ~ 1(~0.3) in the electron (hole) band. Moreover, thermal-conductivity measurements give evidence of a distinct phase line below the upper critical field, where the Zeeman energy becomes comparable to εF and Δ. The observation of this field-induced phase provides insights into previously poorly understood aspects of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime.

Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/µL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/µL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag.

Association of Cumulative Steroid Dose with Risk of Infection after Treatment for Severe Acute Graft-versus-Host Disease.

This study aimed to characterize the incidence and risk factors of invasive fungal disease, cytomegalovirus infection, other viral diseases, and gram-negative rod infection after glucocorticoid treatment for severe acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation and to elucidate the associations of cumulative steroid dose with the risks of individual infections. The study cohort included 91 consecutive patients who developed maximum grades III and IV acute GVHD at our center. The mean cumulative prednisolone-equivalent dose was 41 mg/kg during the first 4 weeks. The cumulative incidence rates of fungal disease, cytomegalovirus disease, other viral diseases, and gram-negative rod infection at 6 months after glucocorticoid treatment were remarkably high, at 14%, 21%, 28%, and 20%, respectively. GVHD within 26 days after transplantation and low lymphocyte count at GVHD treatment were associated with increased risks of several infections. Cumulative prednisolone-equivalent steroid doses ≥ 55 mg/kg during the first 4 weeks were associated with an increased risk of fungal disease (hazard ratio, 3.65; P = .03) and cumulative doses ≥ 23 mg/kg were associated with an increased risk of non-cytomegalovirus viral diseases (hazard ratio, 4.14; P = .02). Strategies to reduce the risk of infectious complications are needed, particularly for patients who have risk factors and those who receive high cumulative steroid doses.

Late Mortality and Causes of Death among Long-Term Survivors after Allogeneic Stem Cell Transplantation.

We sought to assess the late mortality risks and causes of death among long-term survivors of allogeneic hematopoietic stem cell transplantation (HCT). The cases of 11,047 relapse-free survivors of a first HCT at least 2 years after HCT were analyzed. Standardized mortality ratios (SMR) were calculated and specific causes of death were compared with those of the Japanese population. Among relapse-free survivors at 2 years, overall survival percentages at 10 and 15 years were 87% and 83%, respectively. The overall risk of mortality was significantly higher compared with that of the general population. The risk of mortality was significantly higher from infection (SMR = 57.0), new hematologic malignancies (SMR = 2.2), other new malignancies (SMR = 3.0), respiratory causes (SMR = 109.3), gastrointestinal causes (SMR = 3.8), liver dysfunction (SMR = 6.1), genitourinary dysfunction (SMR = 17.6), and external or accidental causes (SMR = 2.3). The overall annual mortality rate showed a steep decrease from 2 to 5 years after HCT; however, the decrease rate slowed after 10 years but was still higher than that of the general population at 20 years after HCT. SMRs in the earlier period of 2 to 4 years after HCT and 5 years or longer after HCT were 16.1 and 7.4, respectively. Long-term survivors after allogeneic HCT are at higher risk of mortality from various causes other than the underlying disease that led to HCT. Screening and preventive measures should be given a central role in reducing the morbidity and mortality of HCT recipients on long-term follow-up.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

Astrocytes Release Polyunsaturated Fatty Acids by Lipopolysaccharide Stimuli.

We previously reported that levels of long-chain fatty acids (FAs) including docosahexaenoic acids (DHA) increase in the hypothalamus of inflammatory pain model mice. However, the precise mechanisms underlying the increment of free fatty acids (FFAs) in the brain during inflammation remains unknown. In this study, we characterized FFAs released by inflammatory stimulation in rat primary cultured astrocytes, and tested the involvement of phospholipase A2 (PLA2) on these mechanisms. Lipopolysaccharide (LPS) stimulation significantly increased the levels of several FAs in the astrocytes. Under these conditions, mRNA expression of cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in LPS-treated group increased compared with the control group. Furthermore, in the culture media, the levels of DHA and arachidonic acid (ARA) significantly increased by LPS stimuli compared with those of a vehicle-treated control group whereas the levels of saturated FAs (SFAs), namely palmitic acid (PAM) and stearic acid (STA), did not change. In summary, our findings suggest that astrocytes specifically release DHA and ARA by inflammatory conditions. Therefore astrocytes might function as a regulatory factor of DHA and ARA in the brain.

Comparison of Outcomes for Pediatric Patients With Acute Myeloid Leukemia in Remission and Undergoing Allogeneic Hematopoietic Cell Transplantation With Myeloablative Conditioning Regimens Based on Either Intravenous Busulfan or Total Body Irradiation: A Report From the Japanese Society for Hematopoietic Cell Transplantation.

Pediatric patients with acute myeloid leukemia (AML) mainly receive myeloablative conditioning regimens based on busulfan (BU) or total body irradiation (TBI) before allogeneic hematopoietic cell transplantation (allo-HCT); however, the optimal conditioning regimen remains unclear. To identify which of these regimens is better for pediatric patients, we performed a retrospective analysis of nationwide registration data collected in Japan between 2006 and 2011 to assess the outcomes of patients receiving these regimens before a first allo-HCT. Myeloablative conditioning regimens based on i.v. BU (i.v. BU-MAC) (n = 69) or TBI (TBI-MAC) (n = 151) were compared in pediatric AML patients in first or second complete remission (CR1/CR2). The incidences of sinusoid obstruction syndrome, acute and chronic graft-versus-host disease, and early nonrelapse mortality (NRM) before day 100 were similar for both conditioning groups; however, the incidence of bacterial infection during the acute period was higher in the TBI-MAC group (P = .008). Both groups showed a similar incidence of NRM, and there was no significant difference in the incidence of relapse between the groups. Univariate and multivariate analyses revealed no significant differences in the 2-year relapse-free survival rates for the i.v. BU-MAC and TBI-MAC groups in the CR1/CR2 setting (71% versus 67%, P = .36; hazard ratio, .73; 95% CI, .43 to 1.24, respectively). TBI-MAC was no better than i.v. BU-MAC for pediatric AML patients in remission. Although this retrospective registry-based analysis has several limitations, i.v. BU-MAC warrants further evaluation in a prospective trial.

Donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene: detailed immunological function following add-back after haplo-identical transplantation.

BACKGROUND AIMS: Haplo-identical hematopoietic stem cell transplantation (HSCT) with add-back of donor lymphocytes expressing the herpes simplex virus thymidine kinase suicide gene (TK cells) is one of the most widely applied promising new gene therapy approaches. However, the immunological status of added-back TK cells after HSCT has yet to be well characterized. METHODS: We investigated TK cells through the use of flow cytometry, T-cell receptor (TCR) Vß repertoire spectratyping and linear amplification-mediated polymerase chain reaction followed by insertion site analysis in a patient enrolled in our clinical trial. RESULTS: A comparison of onset with remission of acute graft-versus-host disease confirmed that TK cells were predominantly eliminated and that proliferative CD8(+) non-TK cells were also depleted in response to ganciclovir administration. The TCR Vß-chain repertoire of both TK cells and non-TK cells markedly changed after administration of ganciclovir, and, whereas the TCR repertoire of non-TK cells returned to a normal spectratype long after transplantation, that of TK cells remained skewed. With the long-term prophylactic administration of acyclovir, TK cells oligoclonally expanded and the frequency of spliced variants of TK cells increased. Known cancer-associated genes were not evident near the oligoclonally expanded herpes simplex virus (HSV)-TK insertion sites. CONCLUSIONS: We demonstrate obvious differences in immunological status between TK cells and non-TK cells. In addition, we speculate that long-term prophylactic administration of acyclovir increases the risk of oligoclonal expansion of spliced forms of TK cells.

Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

Eph receptor A10 has a potential as a target for a prostate cancer therapy.

We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here.

Positive impact of chronic graft-versus-host disease on the outcome of patients with de novo myelodysplastic syndrome after allogeneic hematopoietic cell transplantation: a single-center analysis of 115 patients.

To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo-HCT at our center. Eighty one patients received reduced-intensity conditioning (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although the RIC group was significantly older and included more patients with poor cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between the two groups. In a multivariate analysis, covariates associated with a worse OS were the French-American-British stage of refractory anemia excess blasts in transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20% or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark analyses, we found that the presence of cGVHD significantly improved OS in high-risk patients or the RIC group. However, there was no difference in OS between those with and without cGVHD among low-risk MDS patients. These findings suggest that the graft-versus-leukemia effect may be more beneficial in high-risk patients who do not receive intensive preparative regimens.

Involvement of the long-chain fatty acid receptor GPR40 in depression-related behavior.

The functional role of brain G protein-coupled receptor 40 (GPR40) remains unclear. We investigated GPR40 signaling in depression-related behavior in mice via the forced swim test. A repeated but not a single intracerebroventricular administration of the GPR40 agonist, GW9508, reduced the duration of immobility behavior. Moreover, the levels of hippocampal non-esterified docosahexaenoic acid and arachidonic acid were decreased immediately after the forced swimming. These results suggested that brain GPR40 signaling may regulate depression-related behavior.