International Journal of Hematology最新文献

The development of effective and safe therapies for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan remains a key focus of research. We conducted a phase 2, open-label, multicenter, non-comparative study to evaluate the safety and efficacy of fixed-duration venetoclax plus ibrutinib in 10 patients with previously untreated CLL/SLL (7 CLL/3 SLL). The primary endpoint was the rate of complete remission (CR)/CR with incomplete marrow recovery (CRi) assessed by the independent review committee (IRC). The median age was 72.5 (range 61-77) years. The IRC-assessed CR/CRi rate was 60.0% (95% confidence interval: 26.2-87.8%), exceeding the pre-specified efficacy threshold of 10% and meeting the primary endpoint. The median venetoclax treatment duration was 11.0 (range 2.1-17.7) months. At a median follow-up of 20.6 months, the secondary endpoints of median progression-free and overall survival were not estimated. The overall undetectable measurable residual disease rate was 60.0%. All patients experienced treatment-emergent adverse events (TEAEs), including 7 (70.0%) with grade 3/4 and 2 (20.0%) with serious TEAEs, respectively, and 1 discontinued venetoclax because of a TEAE (increased blood creatine phosphokinase). These findings suggest that venetoclax plus ibrutinib has a favorable benefit-risk profile with high efficacy and manageable safety.

Hematopoietic stem cell transplantation (HSCT) recipients are highly susceptible to viral infections, many of which are missed by conventional diagnostic tests owing to limited coverage and slow turnaround times. This single-center, prospective observational study evaluated a rapid multiplex PCR (mPCR) assay to detect 13 DNA viruses for diagnosis and management of post-HSCT viral infections. Between December 2020 and March 2025, 63 HSCT recipients with suspected viral infections underwent mPCR testing of blood (n = 51) or cerebrospinal fluid (CSF) (n = 12) in parallel with standard diagnostics. The mPCR results were reported within 24 h and integrated into clinical decision-making. The etiology was identified in 44 of 51 (86%) blood samples (30 infections) and 9 of 12 (75%) CSF samples (5 infections). mPCR provided the sole etiological diagnosis in 19 of 63 (30%) episodes: 15 of 51 (29%) blood and 4 of 12 (33%) CSF samples. mPCR enabled targeted treatment in 15 of 63 (24%) episodes: 11 of 51 (22%) blood and 4 of 12 (33%) CSF samples. Unexpected infections, such as varicella-zoster virus meningitis and human herpesvirus 7 encephalitis, were identified only by mPCR. Rapid mPCR provided timely, actionable diagnosis and directly influenced the clinical management of post-HSCT patients.

Although chimeric antigen receptor (CAR)-T cell therapies are highly effective for B-cell lymphoma, they frequently cause cytokine release syndrome (CRS). High-grade CRS is serious and may require intensive care, yet reliable early predictive markers remain elusive. To identify risk factors for high-grade CRS, we retrospectively analyzed B-cell lymphoma patients who received CD19 CAR-T cell therapy. Of 106 patients analyzed, CRS occurred in 93 (88%), Grade ≥ 2 CRS in 28 (26%), and Grade ≥ 3 CRS in 6 (6%). Reticulocyte counts at infusion were significantly lower in patients who developed Grade ≥ 2 CRS (1.85 vs. 2.80 × 10⁴/µL, p = 0.02). Multivariate analysis identified low reticulocyte count (< 15,000/µL; HR 2.21; 95% CI 1.01-4.86; p = 0.048), high metabolic tumor volume (> 100 mL), and use of axicabtagene ciloleucel as independent risk factors for Grade ≥ 2 CRS. Stratification by the reticulocyte cutoff showed higher 30-day cumulative incidence of CRS in patients with low counts, for both Grade ≥ 2 (42.9% vs. 19.7%, p = 0.012) and Grade ≥ 3 CRS (17.9% vs. 1.3%, p < 0.001). KyoTox-CRS, a risk-scoring system integrating these factors, effectively stratified these CRS risks. Early prediction of high-grade CRS based on the reticulocyte count at infusion may help to guide optimal risk-based management of CAR-T cell therapy.

Evidence regarding the efficacy and safety of DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) therapy for relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) is critically lacking. This retrospective study analyzed 78 patients with r/r DLBCL who received DeVIC therapy at a single institution. The overall response rate was 37.2%, comprising 21.8% complete and 15.4% partial responses. A total of 15 (19.2%) patients proceeded to transplantation or cellular therapy. The 3-year overall survival and progression-free survival were 28.2 and 18.0%, respectively. Multivariable analyses identified refractoriness to prior therapy and elevated serum lactate dehydrogenase (LDH) levels as significant predictors of poor response and survival. Decision tree models confirmed these findings, revealing that relapsed cases with low LDH had the most favorable outcomes. Hematological toxicities were frequent, with febrile neutropenia in 52.6% and infection-related mortality in 3.8% of patients. Those with central nervous system involvement had a dismal prognosis, underscoring the need for novel therapeutic approaches. These findings highlight the potential role of DeVIC therapy in selected patients with r/r DLBCL and provide insights into optimizing bridging strategies and subsequent immunocellular therapies.

Central nervous system (CNS) involvement in plasma cell neoplasms is rare and associated with poor prognosis, and indications for cerebrospinal fluid (CSF) analysis remain undefined. We describe three cases: two with advanced-stage, high-risk cytogenetics, and one stage I case meeting criteria for plasma cell leukemia (PCL). In two patients, delayed CSF evaluation after neurological symptoms led to rapid deterioration, whereas early CSF analysis in an asymptomatic patient enabled timely diagnosis. One case worsened acutely after treatment with plerixafor. These findings suggest that CSF evaluation may merit consideration in high-risk patients, including those with PCL or before plerixafor administration.

Mantle cell lymphoma (MCL) associated with immunodeficiency or dysregulation (IDD) has not been linked to the use of JAK inhibitors (JAKi). While the development of lymphoma in patients receiving JAKi for rheumatoid arthritis and psoriatic arthritis (PsA) has been reported, no MCL patients have been reported. A 73-year-old man receiving methotrexate (MTX) for at least a 17-year history of PsA developed cervical lymphadenopathy. Biopsy revealed MCL, and lymphadenopathy resolved following cessation of MTX. Upadacitinib (UPA), a JAK-1 inhibitor, was initiated as an alternative treatment for PsA. While it was very effective, it also led to recurrent lymphadenopathy. Upon discontinuation of UPA, lymphadenopathy regressed. This pattern occurred a third time, ultimately leading to significant exacerbation. A second biopsy revealed histology associated with the pleomorphic variant of MCL. In situ hybridization for Epstein-Barr virus-encoded small RNA and immunohistochemistry for human herpesvirus 8 were negative. A FISH analysis detected the IGH::CCND1 fusion, confirming the diagnosis. The clinical staging was Ann Arbor stage Ⅱ, and the MCL International Prognostic Index indicated intermediate risk. Partial response was achieved with radiotherapy. Although JAKi and MCL are uncommon in the established IDD setting, their potential relationship warrants consideration.

Treatment-free remission (TFR) is an emerging goal for patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKI). However, long-term TFR durability in real-world settings remains understudied. The J-SKI study, a large observational study, was conducted to evaluate long-term TFR outcomes in Japanese patients with CML. This interim analysis included 795 eligible patients from the prospective (n = 283) and retrospective (n = 512) cohorts. With a median follow-up of 32 months (range 0.8-168) after TKI discontinuation, the 5-year TFR rate was 65.2% (95% confidence interval [CI]: 59.6-70.6%). Among patients who experienced molecular relapse, 99% (95% CI: 97-100%) regained a major molecular response after resuming TKI therapy, with no observed disease progression. Multivariate analysis identified the duration of deep molecular response (DMR) as the sole independent predictor of successful TFR, with each additional year of DMR reducing the relapse risk by 12.5% (HR: 0.875, p < 0.0001). A second TFR attempt was successful in 41% (95% CI: 22-59%) of the 32 patients. This study demonstrated that TKI discontinuation is a safe and feasible strategy in a real-world clinical setting. A sustained DMR is critical for TFR success, supporting its importance as a key therapeutic objective.

Aim and purpose: This study aimed to investigate the relationship between myeloma cell maturity, clinical profiles, and treatment outcomes in patients with multiple myeloma (MM).

Patients and methods: The J-CHARGE-MM database includes data from 1200 MM patients diagnosed between January 2011 and January 2023. Immunophenotyping by flow cytometry using antibodies against CD38, CD49e, and MPC-1 was used to evaluate myeloma cell maturity.

Results: Out of 969 patients evaluable for myeloma cell maturity, 115 were classified as mature type, 626 as intermediate type, and 228 as immature type. Patients with the immature type were more likely to have the IgG type and 1q21 gain/amplification. Treatment response and outcome analysis showed that patients with the immature type had lower response rates and worse time to next treatment (TTNT) with bortezomib-based therapy compared to those with the mature or intermediate type. Lenalidomide-based therapy partially mitigated the adverse impact of the immature type. However, daratumumab combination therapy showed higher response rates and better TTNT, which was almost equivalent between the mature/intermediate and immature types.

Conclusion: Stratifying patients with MM based on myeloma cell maturity provides meaningful information for choosing the best treatment strategy and improving patient outcomes.

Venetoclax (VEN) has emerged as a frontline therapy for older adults with acute myeloid leukemia (AML), yet its advantages over intensive chemotherapy (IC) remain uncertain. This single-center retrospective study compared the efficacy and safety of VEN-based regimens (n = 35) with IC (n = 54) in newly diagnosed patients with AML aged ≥ 65 years. No significant differences were found in the primary endpoints of median event-free survival (190.0 vs. 84.5 days, p = 0.20) or median overall survival (324 vs. 273 days, p = 0.30). However, the VEN group demonstrated a significantly higher overall response rate (71% vs. 48%, p = 0.03) and a more favorable safety profile. Notably, 30-day mortality was 0% in the VEN group compared to 16.7% in the IC group. Rates of Grade ≥ 3 cytopenias and febrile neutropenia were also significantly lower in the VEN group. These findings suggest that VEN-based regimens offer comparable survival with improved response rates and reduced early mortality, supporting their use as an effective and safer alternative to IC even for some IC-eligible older adults with AML, though these conclusions are drawn from a single-center, retrospective study.