Dasatinib is superior to imatinib in adult Ph + ALL: a propensity score-matched analysis of pooled JALSG trial data.

This study compared dasatinib and imatinib in adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). Using pooled data from three JALSG prospective trials (Ph + ALL202, Ph + ALL208, Ph + ALL213), we analyzed outcomes for 206 patients aged 15-64 years treated with dasatinib (n = 74) or imatinib (n = 132) in combination with chemotherapy. We applied propensity score matching (1:1) and inverse probability of treatment weighting to minimize selection bias and balance baseline characteristics.

Intravenous umbilical cord-derived mesenchymal stromal cell therapy may improve overall survival in Japanese patients with idiopathic pneumonia syndrome after hematopoietic stem cell transplantation: a multicenter, single-arm, phase II trial.

Idiopathic pneumonia syndrome (IPS) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has a poor prognosis. Although IPS is often treated with steroids, the disease can become resistant to or dependent on steroid treatment, and there is no effective cure for patients with refractory or steroid-dependent IPS. This multicenter, open-label, single-arm, phase II clinical trial investigated the efficacy and safety of HLC-001 (allogeneic umbilical cord-derived mesenchymal stromal cells) in patients with progressive steroid-dependent or refractory IPS after HSCT.

Daratumumab (anti-CD38)- and elotuzumab (anti-SLAMF7)-based treatments for refractory POEMS syndrome: a single-center case series.

Objectives: The survival and neurological prognosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome have been substantially improved by peripheral blood stem cell transplantation and immunomodulating agents since the 2000s. However, some patients with POEMS syndrome are refractory to these treatments. This study aimed to evaluate the efficacy and safety of monoclonal antibody therapy with daratumumab (anti-cluster of differentiation 38) and elotuzumab (anti signaling lymphocytic activation molecule family member 7) for POEMS syndrome.

Clinical outcomes of Japanese patients treated with out-of-specification tisagenlecleucel in a phase 3b trial.

Background: The final manufactured tisagenlecleucel product should meet the commercial product release specifications to ensure the quality in terms of safety, purity, identity, and potency. However, it may occasionally fail to meet these specifications due to the nature of patient-derived cells with variable properties as starting material and the complex manufacturing process. The final product that does not meet at least one of the commercial release specifications is referred to as "out-of-specification" (OOS).

Regulation of H3K4me3 breadth and MYC expression by the SETD1B catalytic domain in MLL-rearranged leukemia.

Histone H3 lysine 4 trimethylation (H3K4me3) is abundant in mixed-lineage leukemia-rearranged (MLL-r) acute myeloid leukemia (AML) cells; however, the responsible enzymes and their roles remain unclear. This study aimed to identify the modifier responsible for high H3K4me3 modification in MLL-r leukemia and its downstream targets essential for the cell proliferation. Here, we performed a CRISPR-tiling screen against known H3K4 methylation modifiers in an MLL-r AML model.

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.

Prognostic impact of TET2 mutations in patients with acute myeloid leukemia: HM-SCREEN-Japan 01 and 02 study.

Ten-eleven translocation-2 (TET2) gene mutations are observed in 12-20% of adult patients with acute myeloid leukemia (AML). The prognostic impact of TET2 mutations in patients with AML and myelodysplastic syndromes has been reported in several studies; however, their results remain controversial. Therefore, we aimed to analyze the prevalence and significance of TET2 mutations in patients with AML.

Increased Non-Relapse Mortality in Older People With Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine and Myeloablative Dose of Busulfan-Based Regimen.

Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included.

Clinical Impact of Osteolytic Bone Lesions in POEMS Syndrome: A Single-Center Experience of 114 Patients.

POEMS syndrome is a multisystemic disease associated with monoclonal plasma cell disorders. Although the presence of bone lesions is included in the diagnostic criteria, their precise manifestations remain unknown. Here, we retrospectively analyzed the bone lesions in patients with POEMS syndrome and evaluated their clinical features.

SARS-CoV-2 infection-induced immune thrombocytopenia in a patient with orthotopic heart transplantation: A case report and literature review.

Unlabelled: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet counts with increased risk of bleeding. In particular, ITP induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been increasingly reported. Since immunosuppressive regimens in organ transplantation are often the primary cause of increased risk of infection, ITP following solid organ transplantation has occasionally been observed.

A practice-oriented genome-profiling study for acute myeloid leukemia using the novel HANDLE system: HM-screen-JAPAN02.

HM-SCREEN-Japan is a multicenter collaborative project in Japan to evaluate the clinical utility of a cancer genome panel in the treatment of acute myeloid leukemia (AML). The HM-SCREEN-JAPAN02 study used the Amoy Myeloid Panel with the HANDLE system, which enables efficient and rapid sequencing, as the genomic testing kit. The Amoy Myeloid Panel targets 53 genes with established clinical significance or high prevalence.

Nelarabine-combined chemotherapy improves outcome of T-cell acute lymphoblastic leukemia but shows more severe neurotoxicity: JALSG T-ALL213-O.

We investigated the effectiveness and safety of nelarabine (NEL)-combined chemotherapy for newly diagnosed adult T-cell acute lymphoblastic leukemia (T-ALL) patients. We conducted a phase II trial, T-ALL213-O, where adult T-ALL patients aged 25 to 64 were treated by a regimen based on that used in our previous study, ALL202-O. The main modifications from ALL202-O to T-ALL213-O were as follows: (1) NEL-combined chemotherapy, instead of consolidation (C)1, was used for non-complete remission (CR) patients after induction therapy (IND)1 as IND2; (2) NEL treatments were inserted into C3 and C5 on day 29.

Outcome of donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation in relapsed myelodysplastic syndrome.

Background Aims: Allogeneic hematopoietic stem cell transplantation (HSCT) improves outcomes for myelodysplastic syndrome (MDS) patients, but relapse rates remain high, and postrelapse treatment options are limited. Therefore, this study aimed to identify the factors contributing to the response to donor lymphocyte infusion (DLI) in relapsed MDS patients post-HSCT.

Methods: This study included 107 patients with relapsed and DLI-treated MDS who underwent their first HSCT between 2002 and 2022 and were registered in the Transplant Registry Unified Program.

Clinical impact of airflow obstruction after allogeneic hematopoietic stem cell transplantation.

Criteria for airflow obstruction (AFO) at one year after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pulmonary function tests (PFTs) are more stringent than the bronchiolitis obliterans syndrome (BOS) criteria of the National Institutes of Health. This single-center, retrospective cohort study evaluated the clinical impact of the AFO criteria at any time after transplantation. In 132 patients who underwent allo-HSCT from 2006 to 2016, the 2-year cumulative incidence of AFO was 35.

Allogeneic stem cell transplant with TBI-based myeloablative conditioning in adolescents and young adults with Philadelphia chromosome-negative ALL treated with pediatric protocols.

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs.

Efficacy and safety of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies inhibiting human factor VIII (hFVIII). This phase II/III open-label study evaluated the safety and efficacy of recombinant porcine factor VIII (rpFVIII, susoctocog alfa) in adults with AHA and severe bleeding episodes in Japan (NCT04580407). The initial rpFVIII dose was 200 U/kg, with subsequent doses based on clinical measures including plasma FVIII activity.

Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.

Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.

A Higher Neutrophil Count Is Associated with Favorable Achievement of Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Who Received Second Generation Tyrosine Kinase Inhibitor as Frontline Treatment.

Background: ABL1 tyrosine kinase inhibitor discontinuation securely became among the therapeutic goal for chronic myeloid leukemia chronic phase patients (CML-CP). To establish successful prognostic factors for treatment-free remission (TFR), it is necessary to diagnose the patients with high-risk molecular relapse, however, a biomarker for the achievement of TFR has not been completely elucidated. Recent investigations have determined that neutrophils function crucially in cancer immunology.

Survival impact of response within the first year in a multicenter prospective observational study of chronic GVHD in a Japanese cohort.

A prospective multicenter observational study of organ response was conducted in patients with chronic GVHD diagnosed by the NIH criteria. When response was assessed at 12 months (12 M) in 118 patients, 74.6% were classified as responders and 25.

Nilotinib vs dasatinib in achieving MR4.5 for de novo chronic myeloid leukemia: the randomized JALSG CML212 study.

Deep molecular response (DMR) is a prerequite for treatment-free remission (TFR) in chronic myeloid leukemia in chronic phase (CML-CP). The JALSG (Japan Adult Leukemia Study Group) conducted a prospective randomized phase 3 CML212 study for de novo CML-CP to compare the cumulative achievement of molecular response 4.5 (MR4.

Superiority of BM over PBSC for recipients with pre-transplant lung dysfunction in HLA-matched allogeneic HCT.

Background Aims: Pre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction.

Methods: We analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs.

Metabolic reprogramming regulated by TRAF6 contributes to the leukemia progression.

TNF receptor associated factor 6 (TRAF6) is an E3 ubiquitin ligase that has been implicated in myeloid malignancies. Although altered TRAF6 expression is observed in human acute myeloid leukemia (AML), its role in the AML pathogenesis remains elusive. In this study, we showed that the loss of TRAF6 in AML cells significantly impairs leukemic function in vitro and in vivo, indicating its functional importance in AML subsets.