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Discusses a study that examined hepatic veno-occlusive disease after stem cell transplantation in Japan. Method of the study; Results and discussion; Conclusion.

Background: Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years., Methods and Results: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; P =0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; P =0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; P =0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; P =0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; P =0.036) at 8 years., Conclusions: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.

Purpose: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup., Study Design: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials., Methods: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891)., Results: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept., Conclusion: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort., (© 2024. The Author(s).)

Purpose: To evaluate efficacy, durability, and safety of faricimab in Japanese patients with diabetic macular edema (DME)., Study Design: Subgroup analysis of 2 global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 trials (YOSEMITE, NCT03622580; RHINE, NCT03622593)., Methods: Patients with DME were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W through week 100. Primary endpoint was best-corrected visual acuity (BCVA) change from baseline at 1 year, averaged over weeks 48, 52, and 56. This is the first time 1-year outcomes between Japanese patients (only enrolled into YOSEMITE) and the pooled YOSEMITE/RHINE cohort (N = 1891) have been compared., Results: The YOSEMITE Japan subgroup included 60 patients randomized to faricimab Q8W (n = 21), faricimab PTI (n = 19), or aflibercept Q8W (n = 20). Consistent with global results, the adjusted mean (95.04% confidence interval) BCVA change at 1 year in the Japan subgroup was comparable with faricimab Q8W (+11.1 [7.6-14.6] letters), faricimab PTI (+8.1 [4.4-11.7] letters), and aflibercept Q8W (+6.9 [3.3-10.5] letters). At week 52, 13 (72%) patients in the faricimab PTI arm achieved ≥ Q12W dosing, including 7 (39%) patients receiving Q16W dosing. Anatomic improvements with faricimab were generally consistent between the Japan subgroup and pooled YOSEMITE/RHINE cohort. Faricimab was well tolerated; no new or unexpected safety signals were identified., Conclusion: Consistent with global results, faricimab up to Q16W offered durable vision gains and improved anatomic and disease-specific outcomes among Japanese patients with DME., (© 2023. Japanese Ophthalmological Society.)

Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12 568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DRβ1 plays a key role in the susceptibility to CD (presence of serine being protective, P = 3.6 × 10-67, OR = 0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C*12:02, HLA-B*52:01 and HLA-DRB1*1502 (P = 1.2 × 10-28, OR = 4.01 [3.14-5.12]).

Objectives: Our aim was to assess midterm safety and clinical outcomes of intracoronary infusion of cardiosphere-derived cells (CDCs) after staged palliation in patients with hypoplastic left heart syndrome (HLHS)., Methods: In this prospective, controlled study, 14 consecutive patients with HLHS who were undergoing 2- or 3-stage surgical palliations were assigned to receive intracoronary CDC infusion 1 month after cardiac surgery (n = 7), followed by 7 patients allocated to a control group with standard care alone. The primary end point was to assess procedural feasibility and safety; the secondary end point was to evaluate cardiac function and heart failure status through 36-month follow-up., Results: No complications, including tumor formation, were reported within 36 months after CDC infusion. Echocardiography showed significantly greater improvement in right ventricular ejection fraction (RVEF) in infants receiving CDCs than in controls at 36 months (+8.0% ± 4.7% vs +2.2% ± 4.3%; P = .03). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P = .04), lower incidence of unplanned catheter interventions (P = .04), and higher weight-for-age z score (P = .02) at 36 months relative to controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 36 months were negatively correlated with age, weight-for-age z score, and RVEF at CDC infusion., Conclusions: Intracoronary CDC infusion after staged procedure in patients with HLHS is safe and improves RVEF, which persists during 36-month follow-up. This therapeutic strategy may enhance somatic growth and reduce incidence of heart failure., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function., Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome., Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007)., Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT01273857., (© 2014 American Heart Association, Inc.)

This study was performed to assess the probability of finding HLA-matched donors for Korean and Japanese patients from unrelated marrow donor registries of both countries. A simulation study of donor search was carried out using the donor pools of the Korean Marrow Donor Program (KMDP) with 10,244 and the Japan Marrow Donor Program UMDP) with 53,411 HLA-A, -B, -DR typed donors. The records of a total of 184 actual Korean patients and 1,302 simulated Japanese patients were searched and A, B, DR-matched donors were found for 28% of Korean and 76% of Japanese patients from the KMDP and JMDP pools, respectively. Of those patients who could not find matched donors in the registry of their own country, 30% of Koreans could find matched donors in the JMDP and 10% of Japanese in the KMDP pools. It can be concluded that future international collaboration between Korea and Japan would be very effective for unrelated bone marrow transplantations.

The fusion gene (se(fus)) is a null allele of the secretor type alpha (1, 2) fucosyltransferase gene (FUT2) and was first found in a Japanese population. It has not yet been reported in any other ethnic population. In the present study, we investigated the distribution of the fusion gene of the FUT2 locus in five populations from three ethnic groups in East Asia. The fusion gene was found in two additional Japanese populations with a high frequency (0.0551 in Okinawa and 0.0792 in Akita) and, for the first time outside Japan, in a Korean population, at a very low frequency (0.0063 in Seoul). In contrast, we found no fusion gene in two Chinese populations. These findings showed that the FUT2 fusion gene was ubiquitous in Japanese, but was rare in neighboring populations, suggesting that the FUT2 fusion gene had emerged from within the Japanese. Additionally, a new null allele with a C-to-T substitution at nucleotide 658 was found in one individual native of southern China.

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.