Cytokine release syndrome (CRS) remains a major toxicity of chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL), and robust pre-infusion predictors are needed for risk-adapted management. We retrospectively analysed LBCL patients in the Japanese nationwide registry who underwent CD19 CAR-T-cell therapy between 2019 and 2024. Among 900 patients (median age 62 years), cumulative incidences of CRS within 30 days after infusion were 75.0% for any grade, 20.8% for grade ≥ 2 and 14.0% for grade ≥ 3. In multivariable analysis, lower estimated glomerular filtration rate (eGFR) (adjusted hazard ratio [aHR] 1.108 per 10 mL/min per 1.73 m2 decrease; 95% confidence interval [CI] 1.015-1.209; p = 0.022), higher ferritin (aHR 1.006 per 100 ng/mL; 95% CI 1.001-1.010; p = 0.016), C-reactive protein (CRP) (aHR 1.142 per mg/dL; 95% CI 1.091-1.195; p < 0.001) and lactate dehydrogenase (LDH) (aHR 1.073 per 100 U/L; 95% CI 1.008-1.142; p = 0.028) independently predicted grade ≥ 2 CRS. We then built a four-factor CRS pre-infusion risk evaluation model, cytokine release syndrome-pre-infusion risk evaluation (CRS-PRE), that stratified grade ≥ 2 CRS risk into low, intermediate and high groups with incidences of 2.8%, 26.0% and 50.0% respectively. Decreased eGFR, a surrogate of host renal reserve, with elevated ferritin, CRP and LDH emerged as predictors of high-grade CRS. The CRS-PRE may facilitate risk-adapted monitoring and intervention in clinical practice.
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.
CD34+ cell dose is believed to impact the outcomes of allogeneic peripheral blood stem cell transplantation (PBSCT), yet the optimal dose remains unclear. We retrospectively reviewed 2407 adult patients with acute myeloid leukaemia who underwent their first related PBSCT between 2000 and 2019. The median infused CD34+ cell dose was 3.67 × 106/kg. Patients were divided into three groups based on infused CD34+ cell dose: low (1.0-2.0 × 106/kg), intermediate (2.0-4.0 × 106/kg) and high (4.0-10.0 × 106/kg) groups. The 5-year overall survival rates were 37.2%, 40.2% and 37.4% in the low, intermediate and high groups respectively (p = 0.176). Although the high-group patients experienced faster neutrophil engraftment, cumulative incidences of infection and primary engraftment failure were comparable across groups. Platelet engraftment was significantly delayed in the low group, with 21.7% failing to engraft at day 100, compared to 14.6% and 13.4% in the intermediate and high groups (p < 0.001). Furthermore, the incidence of secondary graft failure was significantly higher in the low group. In conclusion, a CD34+ cell dose >2.0 × 106/kg improves platelet engraftment and reduces the risk of secondary graft failure but does not confer additional long-term benefits.
BACKGROUND:Subsequent neoplasms (SN) are serious late complications after umbilical cord blood transplantation (UCBT). However, population-based comparisons of the incidence and outcomes of SN between Japan and Europe are lacking. OBJECTIVES:To compare the incidence, types, and outcomes of subsequent neoplasms after unrelated UCBT between Japan and Europe. METHODS:We conducted a retrospective registry-based study using data from the Japanese Society for Transplantation and Cellular Therapy/Japanese Data Center for Hematopoietic Cell Transplantation and Eurocord/European Society for Blood and Marrow Transplantation. Patients who underwent unrelated UCBT between 1998 and 2018 and later developed SN were included in this study. Patients with Fanconi anemia, Diamond-Blackfan anemia, solid tumors as the primary disease, or those who received combined grafts were excluded. Overall survival (OS) was assessed using the Kaplan-Meier method. RESULTS:Among 16,241 (Japan) and 10,358 (Europe) UCBT recipients, 527 (3.2%) and 232 (2.2%) developed SN. The incidence of donor-derived acute leukemia/myelodysplastic syndrome (AL/MDS) was higher in Japan (58%) than in Europe (13%). Solid tumor types differed, with upper gastrointestinal cancers being more frequently observed in Japan (20% versus 5%), while skin (14% versus 8%), thyroid (14% versus 4%), and soft tissue tumors (9% versus 1%) were more common in Europe. Five-year OS after post-transplant lymphoproliferative disorder was significantly higher in Japan than in Europe (48% versus 23%, P < .001), whereas after solid tumors and AL/MDS, it was comparable between the two groups. CONCLUSIONS:Marked regional differences exist in SN type and prognosis after UCBT. The observed variations in donor-derived leukemia and solid tumor types underscore the importance of tailored region-specific surveillance strategies for long-term post-transplant care.
This study aimed to identify patient groups in which myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens induced superior progression-free survival (PFS) in patients with acute myeloid leukemia (AML) in complete remission (CR) using a machine-learning approach. Our study included 3273 patients aged 40–69 with AML in CR. The patients were divided into training (N = 2020) and validation cohorts (N = 1253). We employed a machine learning-based group identification model in the training cohort. Subsequently, in the validation cohort, we estimated the impact of the optimal conditioning group compared with the non-optimal conditioning group on PFS using an inverse probability weight analysis. The developed model was consistent with the eight factors and combinations, and the high score suggested that RIC was more appropriate than MAC. In the validation cohort, 127 patients with high scores and who received RIC and 769 patients with low scores and who received MAC were categorized into the optimal conditioning group (896, 71.5
