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Background Mantle cell lymphoma is considered an aggressive B‐cell lymphoma. The optimal induction regimen remains controversial as no randomized controlled trial has compared the efficacy of different induction therapies. Method Herein, we performed a retrospective analysis of the clinical characteristics of 10 patients who received induction treatment consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) and rituximab, bendamustine, and cytarabine (R‐BAC) at Toranomon Hospital between November 2016 and February 2022. Result Although one patient discontinued R‐BAC therapy due to a rash, the other nine completed the scheduled chemotherapy. All patients achieved complete response, underwent high‐dose chemotherapy and autologous stem cell transplantation, and maintained complete remission with a median follow‐up of 15 months. Hematological adverse events (AEs) occurred in all patients; however, none developed documented infection. There were also no fatal non‐hematological AEs specific to R‐BAC. Conclusion R‐CHOP/R‐BAC may be a good induction therapy for transplant‐eligible patients with mantle cell lymphoma.

The autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell product, lisocabtagene maraleucel (liso‐cel), is administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This analysis assessed safety and efficacy of liso‐cel in Japanese patients with relapsed or refractory (R/R) aggressive large B‐cell lymphoma (LBCL) in Cohort 3 of TRANSCEND WORLD (NCT03484702). Liso‐cel (100 × 106 total CAR+ T cells) was administered 2–7 days after lymphodepletion. The primary efficacy endpoint was objective response rate (ORR; Lugano 2014 criteria) assessed by an independent review committee. Fourteen patients were enrolled; 10 received liso‐cel infusion (median time to liso‐cel availability, 23 days) and were evaluable at data cutoff (median follow‐up, 12.5 months). Grade ≥ 3 treatment‐emergent adverse events were neutropenia (90%), leukopenia (80%), anemia (70%), and thrombocytopenia (70%). All‐grade cytokine release syndrome (CRS) was observed in 50% of patients, though no grade ≥3 CRS events were reported. Grade 1 neurological events occurred in 1 patient but were resolved without any intervention. Prolonged cytopenia (grade ≥ 3 at day 29) was reported for 60% of patients. The ORR was 70%, and complete response rate was 50%. The median duration of response was 9.1 months (95% confidence interval [CI], 2.1—not reached), and overall survival was 14.7 months (95% CI, 1.7—not reached). One patient diagnosed with central nervous system involvement after screening but before liso‐cel infusion, responded to liso‐cel. Liso‐cel demonstrated meaningful efficacy and a manageable safety profile in Japanese patients with R/R LBCL. This analysis assessed safety and efficacy of lisocabtagene maraleucel (liso‐cel), an autologous CD‐19‐directed CAR T‐cell product, in Japanese patients with R/R aggressive LBCL in Cohort 3 of TRANSCEND WORLD (NCT03484702). Liso‐cel demonstrated meaningful efficacy and a manageable safety profile in Japanese patients with R/R LBCL. We also report the first case of a patient who was diagnosed with secondary CNS lymphoma and achieved a response following treatment with liso‐cel.

Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0–46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40–2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14–2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5– + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17–53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.

Invasive fungal infections (IFIs) are associated with considerable morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Despite that epidemiology of IFIs has changed notably by evolution in transplantation procedures as well as preventative strategies, the attributable mortality still remains high, mainly because of delayed initiation of treatment due to its diagnostic difficulty. Hence high-resolution computed tomography and non-culture based adjunctive diagnostic tests such as enzyme-linked immunosorbent assay for galactomannan and (1,3)-β- d -glucan have been incorporated into clinical practice, and global antifungal prophylaxis has been applied particularly to high-risk patients. Newer mold-active agents with higher efficacy and lower toxicity are currently being introduced as prophylaxis, and the combination of these agents are being evaluated as salvage therapy. This review summarizes recent advances in the diagnosis and management of IFIs in HSCT recipients. Further improvement of clinical outcome will be achieved by optimizing diagnostic, prophylactic and therapeutic approach based on individual patient’s risk and situation.

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one of the standard treatments for relapsed/refractory (r/r) non-Hodgkin lymphoma, but benefits across large B-cell lymphoma (LBCL) and nodal peripheral T-cell lymphoma (PTCL) subtypes remain unclear. This single-center retrospective study evaluated outcomes after the first allo-HSCT in 92 adults with r/r aggressive lymphoma (59 and 33 patients with LBCLs and PTCLs, respectively) treated during 2011–2023. The patients’ median age was 51 years; 58.7% had active disease at transplant, and 77.2% received cord blood grafts. With a median follow-up of 7.6 years among survivors, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 31.6% and 27.9%, respectively. Furthermore, the non-relapse mortality (NRM) and relapse/progression rates were 30.8% and 41.3%, respectively. Compared with patients with LBCLs, those with PTCLs showed superior 5-year outcomes (OS: 47.7% vs. 22.4%, P  = 0.03; PFS: 39.7% vs. 21.0%, P  = 0.04) and lower relapse rates (26.9% vs. 49.5%, P  = 0.02), with similar NRM and acute graft-versus-host disease rates. Multivariable models showed that PTCL histology was an independent predictor of improved OS and PFS. These findings suggest that allo-HSCT confers greater long-term benefits in patients with PTCL, supporting its role as an effective option in this subgroup.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2 years after transplantation, and followed them for up to 10 years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19 + B cells was faster after U-CBT than after U-BMT in the first 5 years after transplantation. Although CD4 + T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5 years post-transplantation.

Acquired point mutations in the ABL1 gene are widely recognized as a cause of Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia (Ph + B-ALL) that is resistant to tyrosine kinase inhibitors, whereas there are few reports about other types of the ABL1 mutation. Here, we report 2 cases of Ph + B-ALL gaining a partial deletion type mutation of the ABL1 gene (Δ184-274 mutation), which resulted in truncation of the ABL1 molecule and loss of kinase activity. In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation. This is a case report of a truncated ABL1 mutation in 2 patients with Ph + B-ALL.