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Prolonged hematotoxicity is the most common long-term adverse event in chimeric antigen receptor T cell therapy (CAR-T). To evaluate the impact on prolonged cytopenia of inflammatory status after CAR T infusion, we performed a single-center retrospective study and analyzed patients with B cell lymphomas after CAR-T. Among 90 patients analyzed at 90 days after infusion, the cumulative incidence was 57.5% for prolonged neutropenia, 36.7% for anemia, and 49.8% for thrombocytopenia. Patients who experienced cytokine release syndrome (CRS) had significantly higher incidence and longer duration of prolonged cytopenia. In addition, we found that among patients with grade 1 CRS, those with a longer duration of CRS-related symptoms (>5 days; grade 1b in modified CRS grading [m-CRS]) had a significantly higher incidence and longer duration of prolonged cytopenia than those whose CRS-related symptoms resolved within 5 days (grade 1a m-CRS). Multivariate analysis revealed that a higher m-CRS grade (grade 1b or 2; hazard ratio [HR], 2.42), higher peak CRP (≥10 mg/dL; HR, 1.66), longer duration of elevated CRP (≥10 days; HR, 1.83), and a decrease in serum inorganic phosphorus concentration (≥30% from baseline; HR, 1.95) were associated with significantly higher cumulative incidence of prolonged neutropenia, as well as anemia and thrombocytopenia. Using these factors, we developed a new predictive scoring model for prolonged hematotoxicity, the KyoTox a-score, which can successfully stratify the incidence and duration of cytopenia independent of the existing model, CAR-HEMATOTOX, which is based on laboratory data at lymphodepletion. Thus, this newly developed post-CAR-T inflammation-dependent score is accurate and useful for predicting prolonged hematotoxicity., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The use of multiple antimicrobials is one of the major causes of post-transplantation AKI, owing to the potential nephrotoxicity of each agent and of drug-drug interactions (DDIs). No satisfactory reports on DDIs the field of allo-HSCT have been published. We performed a retrospective analysis to compare the incidence of AKI within 100 days post-transplantation. A total of 465 allo-HSCTs in 416 patients were analyzed, and the cumulative incidence of AKI was 40.0%. AKI was associated with significantly reduced overall survival (hazard ratio [HR], 2.66; 95% confidence interval [CI] 1.95 to 3.55; P < .01) and increased transplantation-related mortality (HR, 4.77, 95% CI, 2.90 to 7.88; P < .01). A higher incidence of AKI was significantly associated with the use of ciprofloxacin, cefepime, tazobactam/piperacillin, meropenem, vancomycin, liposomal amphotericin B, ganciclovir, and foscarnet. Among these drugs, combinations of vancomycin plus tazobactam/piperacillin (HR, 2.23; P = .09 for interaction), ganciclovir plus cefepime (HR, 5.93; P = .04), and ganciclovir plus meropenem (HR, 2.63; P = .12) synergistically increased the risk of AKI, whereas combinations involving teicoplanin did not. This is the first report dealing with DDIs after allo-HSCT, indicating that such combinations should be avoided to preserve renal function and reduce AKI-related morbidity and mortality., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The combination of calcineurin inhibitors and short-term methotrexate has been used as a standard graft-versus-host-disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. Mini-dose methotrexate (mini-MTX), consisting of 5 mg/m 2 /d on days 1, 3, 6, and 11, is occasionally selected as an alternative considering toxicity. The significance of day 11 administration remains unclear. We performed a retrospective study of 135 cases of unrelated bone marrow transplantation at our institute between 2006 and 2019 and compared the outcomes between day 11 MTX dose omitted (n = 72) and full-doses of mini-MTX (n = 63). In total cohort, the 4-year overall survival (OS) was 58.7 %, and the omitted group showed poor GVHD/relapse-free-survival (P = .01) with comparable OS (P = .11) and relapse-free survival (P = .11). Human leukocyte antigen (HLA) mismatch is a major risk factor for severe GVHD. We analyzed the impact of omitting day 11 MTX in 2 cohorts from HLA matched or mismatched donors. In both cohorts, the omitted group had a higher risk of severe acute and chronic GVHD. In conclusion, the omission of day 11 MTX was associated with a higher risk of severe GVHD. Therefore the omission of the day 11 dose is not recommended., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)