Koji Nagafuji

Routine identification of Corynebacterium species can be challenging and may complicate investigation of suspected healthcare-associated transmission. We investigated a suspected cluster of blood culture isolates routinely identified as Corynebacterium jeikeium and retrospectively evaluated similarly identified isolates recovered at our hospital. After three patients in a hematology ward had blood cultures yielding C. jeikeium within approximately one month in 2024, pulsed-field gel electrophoresis (PFGE), environmental sampling, and follow-up surveillance were performed. We subsequently reviewed all blood culture isolates routinely identified as C. jeikeium from 2019 to 2025. Ten isolates from 10 unique patients underwent long-read whole-genome sequencing (WGS). Species identity was assessed by average nucleotide identity (ANI) against type-strain genomes, and genomic relatedness by core-genome phylogenetic and pairwise genome analyses. PFGE showed indistinguishable patterns for two cluster-associated isolates. No environmental isolate was identified as Corynebacterium spp., and no additional temporally associated cases were detected. WGS identified all 10 isolates as C. macclintockiae and did not support a single-clone transmission event; the two isolates with indistinguishable PFGE patterns were closely related but not genomically identical. However, direct or indirect transmission between the corresponding patients could not be excluded. These findings support integrating epidemiological investigation, accurate species identification, and high-resolution genomic analysis when evaluating suspected healthcare-associated transmission involving members of the C. jeikeium complex.

Quizartinib is a FMS‐like tyrosine kinase 3 (FLT3) inhibitor indicated for FLT3 internal tandem duplication ( FLT3 ‐ITD)–positive acute myeloid leukemia (AML). We aimed to evaluate quizartinib resistance mechanisms, in addition to efficacy and safety outcomes, in patients with relapsed or refractory FLT3 ‐ITD–positive AML. This multicenter, single‐arm study in Japan (jRCTs071200015) enrolled 18 patients between May 2020 and December 2022. Of these, 15 patients received oral quizartinib (up to 53 mg once daily) for up to 12 cycles of 28 days each, then were followed for 12 months. The primary endpoint was to evaluate the type and rate of quizartinib resistance mutations; secondary endpoints included composite complete remission (CRc) rate, overall response rate (ORR), hematopoietic stem cell transplantation (HSCT) rate, relapse‐free survival (RFS), overall survival (OS), and adverse events (AEs). Among seven evaluable patients, acquired mutations were detected in four patients ( NF1 [R2616X], CSF3R [Q754X], NRAS [G13R], and FLT3 [D835Y] in one patient each), while loss of FLT3 ‐ITD was observed in two patients. In efficacy analyses ( n = 15), CRc rate was 66.7% (95% confidence interval [CI], 38.4–88.2), ORR was 73.3% (44.9–92.2), and median OS was 13.6 months (5.4–not evaluable). Three patients (20.0%) received HSCT directly after quizartinib; in these patients, median RFS was 8.5 months (95% CI, 6.2–not evaluable). Grade ≥ 3 non‐hematologic AEs and grade 1 QT prolongation were each reported in three patients (20.0%). These data offer additional information on potential resistance mechanisms in patients with relapsed or refractory FLT3 ‐ITD–positive AML. Trial Registration: Japan Registry of Clinical Trials (jRCTs071200015).

Comparative data on alternative donor platforms in adolescent and young adult (AYA) allogeneic hematopoietic cell transplantation (HCT) are limited. We conducted a nationwide retrospective registry study in Japan comparing unrelated umbilical cord blood transplantation (UCBT), haploidentical transplantation without post-transplant cyclophosphamide (non-PTCy-haplo), and PTCy-based haploidentical transplantation (PTCy-haplo). The study included 458 patients aged 16-25 years (UCBT, n = 101; non-PTCy-haplo, n = 132; PTCy-haplo, n = 225). The main endpoints were overall survival (OS) and relapse-free survival (RFS); relapse, non-relapse mortality (NRM), graft-versus-host disease (GVHD), and engraftment were also evaluated. UCBT showed the most favorable survival. In multivariable analyses, non-PTCy-haplo was associated with inferior OS and RFS, higher NRM, and a higher incidence of grade II-IV acute GVHD than UCBT. PTCy-haplo was associated with inferior OS versus UCBT but showed no significant differences in RFS, relapse, NRM, acute GVHD, or chronic GVHD. Both haploidentical platforms showed faster neutrophil engraftment than UCBT, and PTCy-haplo also showed faster platelet engraftment. Sensitivity analyses restricted to malignant disease and stratified by conditioning intensity supported these findings. In this AYA cohort, UCBT was associated with the most favorable survival, non-PTCy-haplo showed consistently inferior outcomes, and PTCy-haplo remained a practical alternative when rapid donor availability and early hematopoietic recovery are prioritized.

Post-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.04–2.10; P = 0.031) and lower risk of non-relapse mortality (NRM) (HR, 0.19; 95% CI, 0.05–0.81; P = 0.024) than HID recipients. Multivariable analyses in the entire cohort before PSM confirmed these findings. Fatal infection was the primary cause of NRM in the HID group. This study is the first to demonstrate that, within a homogeneous Asian cohort, MD may have an advantage over HID in PTCy-based allo-HCT in facilitating neutrophil engraftment and reducing the risk of NRM.

Summary: Cord blood transplantation (CBT) is a valuable donor source for patients without human leukocyte antigen (HLA)‐matched donors. While CBT has a lower risk of graft‐versus‐host disease and requires less stringent histocompatibility, it is associated with a higher transplantation‐related mortality (TRM) compared to other donor sources. We hypothesized that assessing the immunogenicity of mismatched HLA could reveal non‐permissive mismatches contributing to increased TRM. We retrospectively analysed 1498 single‐unit CBT cases from 2000 to 2018 across eight Japanese institutions, evaluating the immunogenicity of mismatched HLA using the PIRCHE algorithm to examine binding affinities of HLA‐derived epitopes to donor or recipient HLA. Results indicated that Class I epitopes from mismatched recipient HLA‐B were significantly associated with poor outcomes due to higher TRM and lower neutrophil engraftment, particularly when presented on matched HLA class I. Notably, epitopes from HLA‐B exon 1 showed stronger prognostic significance, with HLA‐B alleles carrying M‐type leader peptides exhibiting higher affinity for these epitopes. Patients with a matched M‐type HLA‐B and Class I epitopes derived from mismatched HLA‐B exon 1 had worse outcomes. These findings suggest that immunogenicity‐informed donor selection could improve CBT outcomes.