Risk Stratification Using DIPSS and Splenomegaly in Myelofibrosis Treated with Pre-Transplant JAK inhibitors.

The Dynamic International Prognostic Scoring System for primary myelofibrosis (DIPSS) has been reported to predict transplant outcomes in myelofibrosis (MF) patients. Recently, the pre-transplant use of JAK inhibitors has become common in clinical practice, but it is unclear whether DIPSS is also useful for predicting transplant outcomes for these patients. In this study, we compared the prognostic impact of DIPSS between MF patients with and without pre-transplant Ruxolitinib therapy.

Prevalence and outcome of VEXAS syndrome in unrelated hematopoietic cell transplantation for bone marrow failure.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) is a recently identified clonal disorder caused by somatic UBA1 mutations in hematopoietic stem cells, leading to bone marrow failure (BMF) and systemic inflammation. We screened 1771 patients with BMF who underwent unrelated hematopoietic cell transplantation in Japan between 1995 and 2020 using multitarget real-time PCR. The diagnoses included myelodysplastic syndrome (MDS, n = 1139), myeloproliferative neoplasms (n = 125), plasma cell neoplasms (n = 23), acquired BMF (n = 395), and congenital BMF (n = 89).

Machine Learning Algorithm to Explore Patients With Heterogeneous Treatment Effects of Clinically Significant CMV Infection and Non-Relapse Mortality After HSCT.

Introduction: Clinically significant cytomegalovirus infection (csCMVi) and non-relapse mortality (NRM) remain serious concerns after allogeneic hematopoietic stem cell transplantation (HSCT), but subpopulations with heterogeneous treatment effects (HTEs) is unclear. Although machine learning (ML) algorithms have recently been applied to HSCT, the methodology has not been well elucidated.

Methods: We developed a ML algorithm which combined weighting procedures and left-truncated and right-censored trees based on classification and regression tree algorithms to fit survival data with time-varying covariates and competing risks comprehensively.

Adjustment of low-dose ATG exposure improves outcomes in allogeneic hematopoietic stem cell transplantation: a prospective multicenter study.

Background Aims: Antithymocyte globulin (ATG) has been used to prevent the incidence of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Low-dose ATG can suppress GVHD without increasing the risk of infectious complications. However, the relationship between ATG exposure and transplant outcomes in low-dose settings remains unclear, particularly in terms of the effect of absolute lymphocyte count (ALC) on its pharmacokinetics.

Impact of graft-versus-host disease on outcomes of cord blood transplantation according to HLA disparity and its prophylaxis type.

This study evaluated the impact of acute graft-versus-host disease (aGVHD) on cord blood transplantation (CBT) outcomes based on human leukocyte antigen (HLA) disparity and GVHD prophylaxis type. Data from 4,196 adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome were analyzed. Patients were classified by HLA mismatch (8/8-6/8, 5/8, and 4/8-2/8) and further by GVHD prophylaxis type (methotrexate [MTX] or mycophenolate mofetil [MMF]).

Safety of hematopoietic stem cell donation from young related donors following the lowering of the age of legal adulthood in Japan.

The Japanese government's recent lowering of the legal adult age to 18 may prompt reconsideration of the minimum age for donors in the Japan Marrow Donor Program. To provide foundational data for decision-makers, this retrospective study analyzed the safety of hematopoietic stem cell donation among 1999 related donors aged 18 to 24 years, using data from the Japanese Data Center for Hematopoietic Cell Transplantation. Severe adverse events (SAEs) occurred in 1.

Classical and Late-Onset SOS/VOD After Allogeneic HSCT: A Japanese Transplant Registry Analysis.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to the 2016 European Society for Blood and Marrow Transplantation criteria, SOS/VOD is classified into classical SOS/VOD and late-onset SOS/VOD, but their similarities and differences remain unclear. Here we retrospectively investigated the incidence, risk factors, and impact on transplant outcomes of classical and late-onset SOS/VOD in 16 518 allo-HSCT recipients using the Japanese nationwide registry data.

Improved Transplant Outcomes With Alternative Donors in Myelofibrosis: A 20-Year Japanese Registry Analysis of Donor Sources and the Impact of Ruxolitinib.

This study of 308 myelofibrosis patients shows that in recent years (2013-2019), alternative donors (mismatched unrelated donors and cord blood) achieved survival rates comparable to HLA-matched donors-a significant improvement compared to earlier years (2000-2012) when outcomes differed substantially. Ruxolitinib showed significant benefits in older patients (≥ 57), particularly with mismatched unrelated donors. Cord blood transplantation outcomes improved with MMF-based GVHD prophylaxis.

Heterogeneity of Survival Benefit Conferred By Letermovir.

Variation in treatment effects based on individual patient characteristics-known as treatment effect heterogeneity or effect modification-has recently gained significant attention. A previous clinical trial and its post hoc analysis suggested that letermovir (LTV) may reduce mortality more in some patients than in others. We hypothesized that the survival benefit of LTV differs according to each patient's specific characteristics.

The impact of the SARS-CoV-2 pandemic on umbilical cord blood transplantation in Japan: insights from an interrupted time series analysis.

The SARS-CoV-2 pandemic disrupted healthcare systems worldwide, particularly affecting hematopoietic stem cell transplantation (HSCT) activities. Understanding the impact of the SARS-CoV-2 pandemic on transplant practices, especially in Japan, where cord blood transplantation (CBT) is prevalent, is crucial. A total of 40,444 allogeneic HSCT cases in Japan between 2011 and 2021 were examined using an interrupted time series analysis to assess the impact of COVID-19 on CBT utilization.

Improved post-transplant outcomes for elderly acute myeloid leukemia patients conditioned with FLU/BU4 rather than conventional MAC regimens.

It is uncertain whether FLU/BU4 regimens, classified as myeloablative conditioning (MAC), improve prognosis compared to conventional MAC regimens (conv-MAC) such as CY/TBI and BU/CY. We compared FLU/BU4 with conv-MAC among 6551 patients (FLU/BU4 905, conv-MAC 5646), including acute myeloid leukemia (AML) patients aged 16-59 who received a first allogeneic transplantation from the Japanese nationwide registry. The primary endpoint was overall survival (OS), while secondary endpoints were treatment-related mortality (TRM) and relapse at 3 years.

Clinical effects of granulocyte colony-stimulating factor administration and the timing of its initiation on allogeneic hematopoietic cell transplantation outcomes for myelodysplastic syndrome.

Granulocyte colony-stimulating factor (G-CSF) accelerates neutrophil recovery after allogeneic hematopoietic cell transplantation (HCT). However, the optimal use of G-CSF and the timing of its initiation after allogeneic HCT for myelodysplastic syndrome (MDS) according to graft type have not been determined. This retrospective study aimed to investigate the effects of using G-CSF administration and the timing of its initiation on transplant outcomes in adult patients with MDS undergoing allogeneic HCT.

Impact of haplo-donor age on transplant outcomes: a comparative analysis of haploidentical vs cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-matched donors is the gold standard. However, haploidentical stem cell transplantation using posttransplant cyclophosphamide (PTCY-haplo) and cord blood transplants (CBTs) are alternatives when HLA-matched donors are not available. Using Japanese registry data, we evaluated the impact of haploidentical donor age on posttransplant outcomes by comparing PTCY-haplo and CBT.

Adverse Impact of Pre-Transplant Liver Dysfunction in Allogeneic Hematopoietic Cell Transplantation.

Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (n = 503).

HLA-matched related peripheral blood stem cell and bone marrow transplantation with RIC regimens yield comparable outcomes for adult AML.

Introduction: Understanding differences in clinical outcomes between PBSCT and BMT is important, and this study compared outcomes of HLA-matched related PBSCT and BMT using reduced-intensity conditioning (RIC) in adult acute myeloid leukemia (AML) patients.

Methods: Data from 402 patients who underwent either PBSCT ( = 294) or BMT ( = 108) between 2000 and 2022 were analyzed using the Japanese nationwide registry database. The primary endpoint was overall survival (OS), and secondary endpoints included disease-free survival (DFS), non-relapse mortality (NRM), and GVHD.

Myeloablative conditioning in cord blood transplantation for acute myeloid leukemia patients is efficacious only until age 55.

Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity conditioning (RIC), rather than myeloablative conditioning (MAC) regimens allowed elderly patients to be treated safely. However, appropriate intensities of conditioning regimens are still unclear, especially for middle-aged patients. To compare outcomes after RIC and MAC regimens, we analyzed AML patients aged 16 years or older in the Japanese registry database, who underwent single cord unit CBT between 2010-2019.

Post-transplant TKIs for Ph+ ALL: practices to date and clinical significance.

Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022.

Impacts of donor age and HLA mismatch on HCT outcomes differ according to the donor CMV serostatus in unrelated allo-HCT.

In unrelated allogeneic hematopoietic cell transplantation (allo-HCT), older and/or HLA-mismatched donors are known risk factors for survival outcomes. In healthy individuals, cytomegalovirus (CMV) seropositivity is associated with impaired adaptive immune systems. We assessed whether the adverse effects of donor risk factors are influenced by the donor CMV serostatus.

Machine learning evaluation of intensified conditioning on haematopoietic stem cell transplantation in adult acute lymphoblastic leukemia patients.

Background: The advantage of intensified myeloablative conditioning (MAC) over standard MAC has not been determined in haematopoietic stem cell transplantation (HSCT) for adult acute lymphoblastic leukemia (ALL) patients.

Methods: To evaluate heterogeneous effects of intensified MAC among individuals, we analyzed the registry database of adult ALL patients between 2000 and 2021. After propensity score matching, we applied a machine-learning Bayesian causal forest algorithm to develop a prediction model of individualized treatment effect (ITE) of intensified MAC on reduction in overall mortality at 1 year after HSCT.

Different impacts of granulocyte colony-stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type.

We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT.

Reappraising the prognostic relevance of cytogenetic risk in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation.

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.