Hematopoietic Cell Transplantation for Severe Combined Immunodeficiency Patients: a Japanese Retrospective Study.

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).

One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors.

The Worldwide Network of Blood and Marrow Transplantation (WBMT) pursues the mission of promoting hematopoietic cell transplantation (HCT) for instance by evaluating activities through member societies, national registries and individual centers. In 2016, 82,718 first HCT were reported by 1,662 HCT teams in 86 of the 195 World Health Organization member states representing a global increase of 6.2% in autologous HCT and 7.

Difference in outcomes following allogeneic hematopoietic cell transplantation for patients with acute myeloid leukemia and myelodysplastic syndromes.

To evaluate whether outcomes following allogeneic hematopoietic cell transplantation differ according to disease type, a three-way comparison for patients with de novo acute myeloid leukemia (AML) ( = 3318), AML evolving from myelodysplastic syndromes (MDS) ( = 208), and MDS with excess blasts (MDS-EB) ( = 994) was performed. The 5-year probabilities of overall survival (OS) for de novo AML, AML evolving from MDS, and MDS-EB were 60%, 42%, and 41% ( < 0.001), respectively.

Newly proposed threshold and validation of white blood cell count at diagnosis for Philadelphia chromosome-positive acute lymphoblastic leukemia: risk assessment of relapse in patients with negative minimal residual disease at transplantation-a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSTCT.

White blood cell count (WBC) at diagnosis is the conventional prognostic factor in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Nevertheless, little is known about the impact of WBC at diagnosis considering the minimal residual disease (MRD) status at allogeneic hematopoietic cell transplantation (HCT). We evaluated adult patients with Ph ALL who achieved negative-MRD and received HCT in first complete remission between 2006 and 2018.

Optimal treatment for Philadelphia-negative acute lymphoblastic leukemia in first remission in the era of high-intensity chemotherapy.

The optimal treatment for Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) has not been established in the high-intensity chemotherapy era. The outcomes of patients with Ph-negative ALL who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched related or unrelated donor in CR1 (HSCT-MRD group and HSCT-MUD group) were obtained from a Japanese registry database. Patients aged 16-24 years and 25-65 years were analyzed separately, and their outcomes were compared to those of patients who continued high-intensity chemotherapy in CR1 in studies (202U group and 202O group) by the Japan Adult Leukemia Study Group (JALSG).

Prognostic value of measurable residual disease at allogeneic transplantation for adults with core binding factor acute myeloid leukemia in complete remission.

Pretransplant measurable residual disease (MRD) has been shown to be associated with relapse incidence following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). However, it remains less clear whether pretransplant MRD status affects transplant outcomes in core binding factor AML (CBF-AML). We retrospectively evaluated the effect of pretransplant MRD, which was measured by a polymerase chain reaction of RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcripts, on transplant outcomes for a cohort of 959 adult patients with t(8;21) or inv(16) AML treated by allogeneic HCT during complete remission (CR), between 2000 and 2018.

Cord blood index predicts engraftment and early non-relapse mortality in adult patients with single-unit cord blood transplantation.

How to select optimal cord blood (CB) remains an important clinical question. We developed and validated an index of CB engraftment, the cord blood index (CBI), which uses three weighted variables representing cell doses and HLA mismatches. We modeled the neutrophil engraftment time with competing events by random survival forests for competing risks as a function of the predictors: total nucleated cells, CD34, colony-forming units for granulocytes/macrophages, and the number of HLA mismatches at the antigen and allele levels.

NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir.

Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15.

Residual disease is a strong prognostic marker in patients with acute lymphoblastic leukaemia with chemotherapy-refractory or relapsed disease prior to allogeneic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is one of the curative treatment options for acute lymphoblastic leukaemia (ALL). However, the outcomes in patients transplanted without complete remission (non-CR) have not yet been fully reported, and detailed analyses are required to identify subgroups in which optimal prognosis is expected and to optimize pre-transplant therapeutic strategies. Hence, we performed a multicentred retrospective cohort study including a total of 663 adult ALL patients transplanted at non-CR status; the median bone marrow (BM) blast counts at HSCT was 13·2%, and 203 patients (30·6%) were treated at primary induction failure status.

Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type.

Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source.

Experimental Design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia ( = 6,548) between 2007 and 2017 using a Japanese database.

Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome in adolescent and young adult patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curable treatment option for adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS). The study aim was to evaluate epidemiological data and identify prognostic factors for AYA patients with MDS undergoing allogeneic HSCT. Here, 645 patients were selected from patients enrolled in a multicenter prospective registry for HSCT from 2000 to 2015.

Pretransplantation Red Blood Cell and Platelet Transfusion Burden in De Novo Myelodysplastic Syndrome Undergoing Allogeneic Transplantation.

Most patients of myelodysplastic syndrome (MDS) require red blood cell (RBC) or platelet transfusion during their disease courses, which could cause an increased risk of iron overload and alloimmunization. However, it remains less clear whether pretransplantation RBC or platelet transfusion burden affects transplant outcomes in patients with MDS. The objective was to examine the significance of pretransplantation RBC and platelet transfusion burden on transplant outcomes after allogeneic HCT for adults with de novo MDS.

Impact of the combination of donor age and HLA disparity on the outcomes of unrelated bone marrow transplantation.

Impact of donor age considering HLA disparity on hematopoietic cell transplantation (HCT) outcomes has not been fully evaluated. We evaluated 8486 patients who received unrelated bone marrow transplantation (UR-BMT) from 8/8 or 7/8 HLA-matched donors. Compared to 8/8 HLA-matched younger donors (<40 years), 8/8 HLA-matched older donors (subdistribution hazard ratio [SHR], 1.

Allogeneic hematopoietic stem cell transplantation for adult patients with B-cell acute lymphoblastic leukemia with high hyperdiploidy: a retrospective nationwide study.

We compared the transplant outcomes of adult patients with B-cell acute lymphoblastic leukemia characterized by high hyperdiploidy (HeH; 51-65 chromosomes) ( = 29) and those with a normal karyotype ( = 87) by propensity score-matched analysis. There were no significant differences among groups in 3-year probabilities of overall survival (OS, 63.5% vs.

Off-the-shelf bone marrow-derived mesenchymal stem cell treatment for acute graft-versus-host disease: real-world evidence.

Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016.

[Clinical features of tuberculosis among allogeneic hematopoietic stem cell transplantation recipients].

The incidence of tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is 10-40 times higher than that in the general population, which ranges from 0.1% to 5.5%.

Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors.

Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.

Prognostic factors in salvage transplantation for graft failure following allogeneic hematopoietic stem cell transplantation.

Although graft failure (GF) is a fatal complication after allogeneic stem cell transplantation (SCT), no mortality risk assessments after salvage SCT have been reported. We developed a comprehensive prognostic scoring system consisting of patient and comorbidity factors with 470 patients as a training cohort out of 940; these patients underwent salvage SCT for GF. The multivariate analysis demonstrated that older age, poorer performance status, a continuation of antimicrobial treatment, and severe organ dysfunction were independently associated with worse overall survival (OS) and non-relapse mortality (NRM).

Effect of high-dose chemotherapy plus stem cell rescue on the survival of patients with neuroblastoma modified by MYCN gene gain/amplification and remission status: a nationwide registration study in Japan.

In high-risk neuroblastoma, the presence of an MYCN gain/amplification (MYCN-GA) is not always a risk factor of cancer-specific death. We herein examined the effect modification of high-dose chemotherapy with autologous hematopoietic stem cell rescue (HDC-autoSCR) in terms of the interaction between MYCN status and remission status (complete remission or very good partial remission [CR/VGPR] vs. partial remission or less [≤PR]).

In ovo electroporation of chicken limb bud ectoderm: Electroporation to chick limb ectoderm: Electroporation to chick limb ectoderm.

Background: Deciphering how ectodermal tissues form, and how they maintain their integrity, is crucial for understanding epidermal development and pathogenesis. However, lack of simple and rapid gene manipulation techniques limits genetic studies to elucidate mechanisms underlying these events.

Results: Here we describe an easy method for electroporation of chick limb bud ectoderm enabling gene manipulation during ectoderm development and wound healing.

Repeated mutation of a developmental enhancer contributed to human thermoregulatory evolution.

Humans sweat to cool their bodies and have by far the highest eccrine sweat gland density among primates. Humans' high eccrine gland density has long been recognized as a hallmark human evolutionary adaptation, but its genetic basis has been unknown. In humans, expression of the () transcription factor correlates with the onset of eccrine gland formation.