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Key Clinical Message We report two male siblings with SDS. They have the same compound heterozygous mutations. Only one of the siblings acquired cytogenetic abnormality of i(7q) 2 years after diagnosis, became transfusion‐dependent, and underwent allogeneic hematopoietic stem cell transplantation. These cases indicate that i(7q) is associated with significant cytopenia in SDS patients.

Studies on the effect of cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 4F2 (CYP4F2) polymorphisms on warfarin maintenance dose in children are conflicting. We conducted a systematic review and meta-analysis to evaluate the effect of these polymorphisms on warfarin maintenance dose in children. We searched relevant literature using the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial libraries without any language restrictions from their inception to 23 July 2017. Dose differences are expressed as standardized mean difference (SMD) or mean difference (MD) with 95% confidence intervals (CI). This review was registered in the PROSPERO prospective register of systematic reviews (CRD42015016172). We included a total of nine studies (745 participants) in the meta-analysis. Patients with CYP2C9 *1/*2, *1/*3, *2/*2, *2/*3, or *3/*3 required a lower warfarin maintenance dose compared with patients with CYP2C9 *1/*1 (SMD = −0.610, 95% CI: −0.802 to −0.419, I2 = 0%). Patients with VKORC1-1639GA or AA required a lower warfarin maintenance dose compared with patients with VKORC1-1639GG (SMD = −0.666, 95% CI: −0.887 to −0.445, I2 = 33%). However, no associations were observed between CYP4F2 polymorphisms and warfarin maintenance dose (MD = 0.005 mg/kg/day, 95% CI: −0.006 to 0.015, I2 = 0%). These results were not affected by a sensitivity analysis. Our meta-analysis provides evidence that CYP2C9 and VKORC1 variant statuses affect warfarin maintenance dose in children, but not CYP4F2.

Peripheral blood stem cell transplantation (PBSCT) is being increasingly performed as an alternative to bone marrow transplantation (BMT); however, PBSCT has not been proven to have equivalent outcome to BMT. We conducted a meta-analysis to compare survival rates and treatment-related complications between PBSCT and BMT for pediatric hematologic malignancies. We searched Medline, Embase plus Embase classics, and the Cochrane Central Register of Controlled Trials for the terms "hematopoietic stem cell transplantation" AND "allogeneic transplantation" AND "children", including randomized controlled studies and cohort studies without language limitations. We identified 7 of 5368 studies for inclusion in our meta-analysis. The cohorts of these studies included a total of 4328 patients, 3185 who underwent BMT and 1143 who underwent PBSCT. Five-year overall survival was similar in the 2 groups (PBSCT, 56.2%; BMT, 63.5%; relative risk [RR], 1.17; 95% confidence interval [CI], .91 to 1.52), as was the 5-year event-free survival (PBSCT, 49.9%; BMT, 57.2%; RR, 1.14; 95% CI, .93 to 1.39). The incidences of nonrelapse mortality and chronic graft-versus-host disease were higher in the PBSCT group compared with the BMT group (RR, 1.73; 95% CI, 1.50 to 1.99 versus RR, 1.55; 95% CI, 1.18 to 2.03). This meta-analysis found insufficient evidence to conclude that peripheral blood stem cells are equivalent to bone marrow. The results indicate that bone marrow can still be a preferred donor source for pediatric hematologic malignancies.

Background Despite its shortcomings, warfarin is still the most commonly prescribed anticoagulant to prevent thromboembolism in children. In adults, numerous studies confirmed the robust relationship between warfarin maintenance doses and single nucleotide polymorphisms of cytochrome P450 2C9 (CYP2C9), vitamin K epoxide reductase (VKORC1), and cytochrome P450 4F2 (CYP4F2). However, their effect in children still remains to be determined. The primary objective of the present systematic review and meta-analysis is to assess the effect of genotypes of CYP2C9, VKORC1, and CYP4F2 on warfarin maintenance dose in children. Methods/design A comprehensive literature review search using the OVID platform will be conducted by a specialized librarian, without language restrictions (i.e., MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials), and all abstracts will be reviewed by two authors. Data abstraction from each eligible study will be extracted individually by two authors (MT and TK), and disagreements will be resolved through discussion with a third person (SI). Critical appraisal of the included analysis of the primary objective will follow the Newcastle–Ottawa Scale, in addition to the Strengthening the Reporting of Genetic Association study (STREGA) statement, and data reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. For the meta-analysis, the presence vs. absence of each genetic polymorphism will be pursued, respectively, using a random effect model with effect size expressed as a mean difference plus 95 % confidence interval. Discussion Our study will provide a comprehensive systematic review and meta-analysis on the potential effects of CYP2C9, VKORC1, or CYP4F2 on the warfarin maintenance dose in children, exploring the feasibility of the development of pharmacogenetic-guided warfarin dosing algorithm for children on oral vitamin K antagonists. Systematic review registration The review has been registered with PROSPERO (registration number CRD42015016172). Electronic supplementary material The online version of this article (doi:10.1186/s13643-016-0280-y) contains supplementary material, which is available to authorized users.

Background: As a source of cells for hematopoietic cell transplantation (HCT), peripheral blood stem cells (PBSC) have become a major alternative to bone marrow, the most common source of cells. A meta-analysis showed that the use of PBSC in adults is not superior with respect to overall survival, and the incidence of chronic graft-versus-host disease (GVHD) is more frequent after PBSC transplantation (PBSCT) than after bone marrow transplantation (BMT). Furthermore, several studies suggested that PBSCT in children results in poor overall survival compared with BMT, and the benefit of PBSCT is controversial. To elucidate this question, we conducted a systematic review and meta-analysis to compare the survival rate and treatment related complications of pediatric patients receiving PBSCT with those receiving BMT. Methods: Based on the pre-defined protocol, MEDLINE, EMBASE plus EMBASE classics, Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform Search Portal and Clinical Trials.gov records were searched from inception through July 25, 2018 with no language restriction. The search terms included "hematopoietic stem cell transplantation" AND "allogeneic transplantation" AND "children". We included randomized control studies or cohort studies. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate study quality. The primary outcome was to evaluate five-year overall survival after HCT. Secondary outcomes were five-year event-free survival after HCT, non-relapse mortality, the incidence of acute and chronic GVHD, and time to platelet and neutrophil engraftment. We performed meta-analyses using random effect models with risk ratios (RR) and a 95% confidence interval (CI). Heterogeneity was assessed using the I-squared statistic and chi-squared test. Publication bias was assessed with funnel plots. Results: We identified a total of 5,248 relevant studies. Seven cohort studies with a total of 4,328 patients (BMT group 3,185 patients and PBSCT group 1,143 patients) were included in the present study. There was no significant difference between PBSCT and BMT for five-year overall survival (RR: 1.17, 95% CI: 0.91-1.52, heterogeneity I2=69%, p=0.22) and five year event free survival (RR: 1.14, 95% CI: 0.93-1.39, heterogeneity I2=57%, p=0.05), respectively. The risk of chronic GVHD in the PBSCT group was higher than those in the BMT group (RR: 1.65, 95% CI: 1.18-2.03, heterogeneity I2=75%, p=0.002). The risk of non-relapse mortality with PBSCT was higher than with BMT (RR: 1.73, 95% CI: 1.50-1.99, heterogeneity I2=0%, p Conclusions: This meta-analysis did not show significant difference in overall survival or relapse between PBSCT and BMT for pediatric hematological malignancy. However, a higher risk of chronic GVHD and transplantation related mortality was associated with PBSCT. Table. Table. Disclosures No relevant conflicts of interest to declare.

Crizotinib treatment for refractory pediatric acute myeloid leukemia with RAN-binding protein 2-anaplastic lymphoma kinase fusion gene

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