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
The C-reactive protein/albumin ratio (CAR), an inflammatory marker, is a useful biomarker for pancreatic cancer. Although disease status is not constant, many inflammatory markers are only classified at the start of treatment. Therefore, biomarker analysis that considers the changes in inflammatory markers during treatment is desirable. We aimed to investigate whether time-dependent changes in the CAR during nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) administration can predict the prognosis of patients with unresectable or recurrent pancreatic cancer (urPC). CAR was measured in 150 participants of the NAPOLEON-2 study, an observational study involving patients with pancreatic cancer receiving NFF, and the patients were stratified by CAR. The CAR at NFF initiation was defined as CAR(1), while the minimum CAR before/throughout NFF administration was defined as CAR(min). Overall survival (OS) of patients in all groups was analyzed. Significant differences in OS between the CAR(1) < 0.54 and ≥ 0.54 groups and between the CAR(min) < 0.54 and ≥ 0.54 groups were observed. The OS was significantly better in the group with CAR(min)/CAR(1) < 0.5 than in the group with CAR(min)/CAR(1) ≥ 0.5. Dynamic changes in CAR were a clinically significant biomarker that considers not only the disease status at the start of treatment but also the response to treatment. CAR monitoring would help understand the disease status and thereby aid patients and physicians alike.
Using data from a nationwide Japanese registry, we evaluated the impact of the total body irradiation (TBI) dose in reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with acute myeloid leukemia (AML). Adults undergoing their first allo-HCT with RIC between 2010 and 2021 were classified into three groups: non-TBI, low-TBI (2 to < 4 Gy), or moderate-TBI (4-8 Gy). Outcomes were analyzed separately for patients in complete remission (CR, n = 1949) and those in the non-CR group (n = 1484). Non-TBI was associated with higher overall mortality than low-TBI (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56 in CR; HR, 1.19; 95% CI, 1.00-1.42 in non-CR). Moderate-TBI showed no significant difference in overall mortality compared to low-TBI (HR, 0.96; 95% CI, 0.80-1.15 in CR; HR, 0.89; 95% CI, 0.77-1.05 in non-CR). Among patients in the CR group with matched sibling donors, moderate-TBI reduced overall mortality (HR, 0.33; 95% CI, 0.17-0.64) and relapse (HR, 0.29; 95% CI, 0.12-0.69). In cord blood transplantation, non-TBI increased relapse in CR (HR, 2.73; 95% CI, 1.48-5.06) and overall mortality in non-CR (HR, 1.62; 95% CI, 1.19-2.19). In haploidentical transplants, non-TBI increased relapse (HR, 5.52; 95% CI, 1.72-17.72 in CR; HR, 1.54; 95% CI, 1.04-2.30 in non-CR). The incidence of secondary primary malignancies did not differ according to the use or dose of TBI. In conclusion, adding low- or moderate-TBI to RIC may improve disease control and survival without increasing non-relapse mortality.
OBJECTIVES:The Klebsiella oxytoca complex inhabits diverse environments, including the human gut, and frequently causes opportunistic infections. This species complex carries the intrinsic β-lactamase gene blaOXY, which confers resistance to ampicillin, and may acquire resistance to other antimicrobials, such as carbapenems, through mobile antimicrobial resistance genes or chromosomal mutations. A subset of the K. oxytoca complex produces cytotoxins associated with antibiotic-associated hemorrhagic colitis. However, the epidemiological and genomic data from Japan are limited. In this study, we aimed to characterize the genomic and phenotypic features of K. oxytoca complex collected nationwide in Japan within the scope of a national antimicrobial resistance surveillance (JARBS) program. METHODS:A total of 46 K. oxytoca complex isolates were obtained through the JARBS program targeting third-generation cephalosporin-resistant and carbapenem-nonsusceptible Enterobacterales in Japan. Whole-genome sequencing, antimicrobial susceptibility testing, plasmid analysis, and cell culture- and mass spectrometry-based cytotoxin detection were performed to investigate antimicrobial resistance and toxin production. RESULTS:Our analyses of clinical isolates revealed diverse genotypes and potential plasmid-mediated mechanisms for blaIMP acquisition. Phenotypic assays revealed multidrug resistance and cytotoxin production in a subset of isolates, and the corresponding genomic determinants were identified. Notably, we identified a multidrug-resistant, cytotoxin-producing lineage belonging to sequence type (ST) 176 that has disseminated across multiple regions of Japan. CONCLUSIONS:This study provides the first nationwide integrated genomic and phenotypic analysis of the K. oxytoca complex in Japan. The spread of the multidrug-resistant, cytotoxin-producing ST176 lineage represents a previously unrecognized high-risk linage in Japan, underscoring the need for continued genomic surveillance.
Despite recent advances, data on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients aged ≥70 years remain limited. We identified prognostic factors and developed a risk score to guide transplant eligibility. Using the Japanese Transplant Registry Unified Management Program, we retrospectively analyzed 929 patients aged ≥70 years who underwent their first allo-HSCT for hematologic malignancies between 2000 and 2022. Prognostic factors were identified by multivariate Cox regression to construct a scoring system. The median patient age was 71 years (range, 70-88), with acute myeloid leukemia being the most common disease. The 2-year overall survival (OS) rate was 34.2%. Multivariate analysis identified age ≥75 years, ATL, lymphoma, high disease risk, hematopoietic cell transplant-specific comorbidity index ≥5, and performance status ≥2 as adverse factors. Using the hazard ratio-based scoring system derived from multivariate analysis, patients were stratified into low- (0), intermediate-1- (1), intermediate-2- (2-3), and high-risk (4-5) groups, with 2-year OS rates of 57.1%, 35.0%, 18.3%, and 2.5%, respectively (p < 0.01). We identified prognostic factors and developed a scoring system stratifying survival in patients aged ≥70 years, potentially facilitating the selection of older candidates most likely to benefit from allo-HSCT.
