This study examined changes in practice patterns and outcomes of allogeneic hematopoietic cell transplantation (HCT) over the past 20 years. Data were analyzed from a Japanese nationwide registry of consecutive adult patients with acute myeloid leukemia who underwent allogeneic HCT between 2001 and 2020. The study population included 17,553 patients, of whom 6653 underwent allogeneic HCT in 2001–2010 and 10,900 in 2011–2020. Patients in the later period were older, were more likely to be in first complete remission, and more frequently received umbilical cord blood transplantation. After adjusting for major covariates, the 2011–2020 cohort had lower risks of overall mortality (hazard ratio [HR], 0.84; 95
BACKGROUND:Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) are associated with poor prognosis, but the impact relative to de novo AML remains controversial. We investigated clinical and genetic features in a multicenter Japanese cohort before CPX-351 approval. METHODS:We retrospectively analyzed 294 patients with newly diagnosed AML registered in the Hokkaido Leukemia Net between 2022 and 2023. Propensity score matching was used to adjust baseline variables. Genetic profiles were assessed in 160 matched patients. RESULTS:In the matched cohort, sAML/AML-MRC did not show inferior overall survival compared with non-sAML/non-AML-MRC (P = 0.90). Adverse karyotypes were the predominant determinant among sAML/AML-MRC. Among sAML/AML-MRC patients, adverse karyotypes were associated with poorer survival than those without adverse karyotypes (P = 0.0075). In contrast, non-sAML/non-AML-MRC groups did not affect survival regardless of adverse karyotypes (P = 0.51). Among 65 patients with ELN 2017 adverse-risk, those with TP53 mutations had markedly shorter survival than those with TP53 wild-type (P = 0.018). CONCLUSIONS:sAML/AML-MRC with an adverse karyotype had a dismal outcome. These findings provide a benchmark for risk stratification in the pre- CPX-351 era.
High-grade B-cell lymphoma with 11q-aberration (HGBCL-11q) is a rare pediatric non-Hodgkin lymphoma. This study assessed outcome in 90 children with HGBCL-11q. With survival rates ≥95%, patients with HGBCL-11q and no predisposition are candidates for deescalated therapy in future prospective trials.
Combination therapy with novel agents is the standard initial treatment for transplant-eligible patients with newly diagnosed multiple myeloma. However, the benefit of additional induction therapy for insufficient response remains unclear. This multicenter prospective study investigated response-adapted intensification with lenalidomide and dexamethasone (LenDex) after cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients who did not achieve a very good partial response (VGPR) or better, followed by autologous stem cell transplantation (ASCT) and lenalidomide maintenance. Sixty-three patients were enrolled at 10 centers between March 2014 and December 2017. Of the 63 patients, 44 underwent ASCT. Six patients (9.5
We recently demonstrated early administration of calcineurin inhibitors (CNIs) after murine allogeneic hematopoietic cell transplantation (allo-HCT) inhibits terminal exhaustion of donor T cells and hampers tolerance induction. However, the role of CNIs in regulating T-cell exhaustion in clinical allo-HCT remains to be clarified. It also remains to be elucidated why posttransplant cyclophosphamide (PTCy) could reduce chronic graft-versus-host disease (cGVHD), despite the administration of CNIs. In this study, we explored the impact of CNIs on donor T-cell exhaustion after PTCy-based haploidentical HCT. In mice, early administration of cyclosporine before PTCy preserved a population of Ly6C⁺ donor T cells with less exhausted characteristics, as has been shown in non-PTCy allo-HCT. In single-cell analysis of clinical samples from patients undergoing HLA-haploidentical peripheral blood stem cell transplantation with PTCy (PTCy-haplo-PBSCT), early administration of tacrolimus prior to PTCy promoted the expansion of effector-like CD8+ intermediate exhausted T cells (Tex-int) and CD4⁺ cytotoxic T cells (CTLs), with the former enriched for both effector- and exhaustion-associated and the latter for effector- and CD4⁺ CTL-specific gene signatures. These subsets retained high responsiveness to TCR stimulation and PD-1 blockade, and their expansion on day 28 predicted subsequent cGVHD. In contrast, delaying tacrolimus administration on day 5 after PTCy-haplo-PBSCT significantly reduced the expansion of these effector-like T cells. These findings indicate early CNI exposure favors the persistence of incompletely exhausted and clonally expanded donor T cells with pathogenic potential. Tex-int and CD4⁺ CTLs may serve as prognostic biomarkers of cGVHD risk and as promising targets for preemptive therapy of cGVHD.
