High serum levels of total carotene, comprising alpha- and beta-carotenes and lycopene, may reduce the risk for cardiovascular disease mortality among the Japanese population.

Graft-versus-host disease (GVHD) occasionally leads to morbidity and mortality but is thought to reduce the risk of relapses in patients with a hematological malignancy. However, information on the effect of GVHD in pediatric leukemia is limited. Using a nationwide registry, we retrospectively analyzed 1526 children who underwent allogeneic stem cell transplantation for leukemia. Grades 0-I acute GVHD were associated with a higher relapse rate at three years after transplantation, at 25.4 and 24.3%, respectively, than grades II, III, or IV acute GVHD at 18.9%, 21.2%, and 2.6%, respectively. In contrast, the overall survival curve of the grades 0 and I GVHD groups (79.0% and 79.5%, respectively) approximated that of the grade II GVHD group (76.3%), and the probability of survival was worst in the severe GVHD groups (66.9% for grade III and 42.5% for grade IV). Chronic GVHD also reduced the relapse risk but conferred no survival advantage. Acute lymphoblastic leukemia was more sensitive to acute GVHD than acute myeloid leukemia (AML) while AML was more sensitive to chronic GVHD. Our study reproduced the preventive effects of GVHD against pediatric leukemia relapses but failed to demonstrate a significant survival advantage.

Background: Lansoprazole, amoxicillin, and clarithromycin are commonly used drugs for eradication of Helicobacter pylori (H. pylori). A few studies reported that the eradication rate was influenced by the functional polymorphism of CYP2C19, whose product metabolizes proton pomp inhibitors including lansoprazole. Methods: This study examined the eradication rate among 67 participants in the polymorphism study who visited Daiko Medical Center, Nagoya University from July 2004 to October 2005. The participants aged 20 to 69 years were classified into three group according to CYP2C19 genotype; rapid metabolizers (RM) with *1*1 genotype, intermediate metabolizers (IM) with *1*2 or *1*3 genotype, and poor metabolizers (PM) with *2*2, *2*3, or *3*3 genotype. For the genotype classification, G681A (681G for *1 and 681A for *2) and G636A (636G for *1 and 636A for *3) were genotyped by PCR with confronting two-pair primers (PCR-CTPP). They were also genotyped for IL-1B T-31C and TNF-A T-1031C by a duplex PCR-CTPP. Results: The eradication rate was 70.0% for RM, 93.9% for IM, and 85.7% for PM. The difference in the rate between RM and IM+PM was statistically significant (p=0.025). The eradication rate was highest for those with IL-1B -31CC; the p value was marginal among the whole subjects (χ 2 =3.78, p=0.05) and not significant among the RM group (χ 2 =1.60, p=0.21). The genotypes of TNF-A T-1031C had no associations with the eradication rate. But among the RM group, the odd ratio (OR) of the TNF-A CT for the eradication rate relative to TT was marginally reduced (OR=0.05, 95% confidence interval, 0.002-1.19). Conclusions:The present study confirmed the low eradication rate for RM. The reproduced finding provides evidence that the CYP2C19 genotype is useful to predict the success of the treatment. For the RM group, alternative regimens expected to be with a higher eradication rate will be recommended, especially to those with the TNF-A -1031C allele.

We analyzed the outcomes of 61 patients with hematologic malignancies who underwent double-unit cord blood transplantation (dCBT) after myeloablative conditioning performed as part of a prospective multicenter phase II study. The conditioning regimen for dCBT included total body irradiation, cyclophosphamide, and granulocyte colony-stimulating factor combined with cytosine arabinoside for myeloid malignancies and with total body irradiation and cyclophosphamide for lymphoid malignancies. The cumulative incidence of neutrophil engraftment after dCBT was 85% (95% confidence interval [CI], 73%-92%). All 51 of the patients who engrafted had complete chimerism derived from a single donor by day +60. Only the degree of HLA disparity in the host-versus-graft direction had an impact on unit dominance. The cumulative incidence of grade II-IV acute graft-versus-host disease was 25% (95% CI, 15%-37%), and that of chronic graft-versus-host disease was 32% (95% CI, 20%-44%). The 1-year cumulative incidence of relapse was 23% (95% CI, 13%-34%), and that of transplantation-related mortality was 28% (95% CI, 17%-39%). With a median follow-up of 41 months, event-free survival was 48% (90% CI, 37%-58%) at 1 year and 46% (90% CI, 35%-56%) at 3 years. Event-free survival at 3 years was 67% (95% CI, 46%-81%) for patients with standard risk and 29% (95% CI, 15%-45%) for those with advanced risk. This study suggests that dCBT after myeloablative conditioning is a promising alternative for adults and large children with hematologic malignancies who need stem cell transplantation but lack a suitable adult donor or an adequate single-unit cord blood graft.

Purpose Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. Methods A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974-2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). Results The 10-year overall survival (OS) of the patients who received HCT in 2006-2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006-2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). ConclusionWe showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID.