International Journal of Hematology最新文献

Acquired pure red cell aplasia (PRCA) affects only the red blood cell lineage and responds to immunosuppressive therapy. Few reports describe the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory PRCA. This study investigated the outcomes of allo-HSCT for PRCA using Japanese nationwide registry data. Eight patients aged 16 years or older who underwent allo-HSCT for acquired PRCA were analyzed. Median ages at diagnosis of PRCA and HSCT were 39.5 (range 19-68) and 47.5 (range 21-68) years, respectively. Stem cell sources and donors were bone marrow (related, n = 2; unrelated, n = 3), umbilical cord blood (n = 2), and peripheral blood stem cells (related, n = 1). All patients achieved neutrophil engraftment with a median time to engraftment of 21 days. Four patients died within 3 months after HSCT; the causes of death were acute myocardial infarction, thrombotic microangiopathy, capillary leak syndrome, and bacterial pneumonia. The remaining four patients were alive and transfusion-independent at a median follow-up of 99.4 months (range 21-148). Allo-HSCT could be a curative treatment option for refractory PRCA. However, early post-transplant mortality is an obstacle, and thus, optimal transplant procedures should be carefully determined for each patient.

Talquetamab is the first G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody approved for relapsed/refractory multiple myeloma (RRMM). We report the first efficacy and safety results of talquetamab in Japanese patients enrolled as a separate cohort in the global MonumenTAL-1 study. Between July 2022 and December 2023, 36 patients were enrolled and received 0.4 mg/kg talquetamab weekly. Median follow-up was 13.4 months. The overall response rate was 77.8% (55.6% achieved complete response or better). Median time to first response was 1.2 months. Twelve-month duration of response, progression-free survival, and overall survival rates were 66.4%, 56.3%, and 74.1%, respectively. On-target, off-tumor adverse events (AEs), including taste-, skin- (non-rash), nail-, and rash-related AEs, were common (80.6%, 66.7%, 55.6%, and 36.1%, respectively) and mostly grade 1/2. Cytokine release syndrome occurred in 75.0% of patients; all events were grade 1/2. The rate of infection was 52.8%; the rate of grade 3/4 infection was 16.7% (one led to death [pneumonia]). One patient discontinued talquetamab and three patients died due to AEs. Results were generally consistent with the global MonumenTAL-1 population, demonstrating talquetamab as an important novel treatment for Japanese patients with RRMM. Clinical trial registration number: NCT03399799/NCT04634552.

Introduction: Busulfan (BU)- and thiotepa (TT)-containing regimens have been approved for autologous stem cell transplantation (ASCT) in central nervous system lymphoma (CNSL). However, optimal doses of these regimens remain unclear. This study retrospectively analyzed the efficacy and toxicity of the Bu2TT regimen.

Method: The study included 12 patients with CNSL who received Bu2TT (BU 3.2 mg/kg, days - 7 and - 6; TT 5 mg/kg, days - 5 and - 4) followed by ASCT at our institution after April 2020.

Results: Four patients were newly diagnosed (primary 3; secondary 1), and eight relapsed (primary 6; secondary 2). The median age was 62 years. Nine patients received high-dose MTX-based regimens as pre-transplant therapy. The other three received tirabrutinib, which was combined with localized radiotherapy (CyberKnife) in one patient. Disease status before ASCT was complete remission (CR) in 7 patients and partial remission in 5. Complications included febrile neutropenia (10/12 patients) and grade 3 anorexia (5/12 patients). Disease status after transplantation was CR in 10 patients and progressive disease in 2. OS and PFS rates at 2 years were 100% and 71%, respectively.

Conclusion: Our data suggest that Bu2TT had acceptable safety and efficacy. These results provide a rationale for further analyses in prospective multi-institutional trials.

Recent advancements in the treatment of multiple myeloma have significantly improved patient outcomes, primarily due to the introduction of various therapeutic modalities. This review focuses on three BCMA-targeted therapies: anti-BCMA CAR-T cell therapy, bispecific antibody (BsAb) therapy, and antibody-drug conjugate (ADC) therapy. BCMA, a membrane-bound protein predominantly expressed on myeloma cells, presents a promising target due to its limited expression in normal tissues, minimizing off-target toxicity. We explore the characteristics, efficacy, and safety profiles of these therapies, highlighting the differences in overall response rates and potential adverse effects. Anti-BCMA CAR-T therapies, such as idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), exhibit varying response rates and durability, with cilta-cel showing a plateau phase suggesting potential long-term remission. In contrast, BsAb therapies like teclistamab and elranatamab provide off-the-shelf treatment options but may lead to T-cell exhaustion. ADC therapy, represented by belantamab mafodotin, poses unique challenges, particularly concerning ocular toxicity. Furthermore, treatment sequencing is critical, as prior exposure to one therapy can influence the efficacy of subsequent treatments. This review emphasizes the necessity of assessing BCMA expression and T-cell exhaustion before initiating therapy, and advocates for carefully constructed treatment regimens to optimize outcomes for patients with multiple myeloma.

The European LeukemiaNet recommendations for the management of chronic myeloid leukemia (CML) consider achievement of major molecular response (MMR) within 12 months to be an optimal response (OR). However, no currently available tool can predict treatment response at diagnosis. This study aimed to develop a predictive scoring tool for OR and subsequent deep molecular response (DMR) using peripheral blood parameters at diagnosis. A retrospective analysis was conducted in 535 patients with CML from the CML Cooperative Study Group database. Patients were categorized into OR (MMR within 12 months; n = 355) and non-OR groups (MMR after 13 months; n = 180). Logistic regression analysis identified white blood cell count, platelet count, eosinophil percentage, and imatinib use as significant predictors of OR. These variables were used to construct a novel score. The score was significantly higher in the non-OR group and showed superior predictive accuracy for OR compared with existing prognostic scores. Furthermore, lower scores correlated with higher rates of DMR achievement. Notably, the score effectively predicted OR achievement among patients with low/intermediate ELTS risk treated with imatinib. This new scoring tool may facilitate individualized treatment selection in CML, guiding upfront tyrosine kinase inhibitor selection and advancing precision medicine.

Acute graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation. Traditional risk stratification based on clinical symptoms provides only modest prognostic accuracy for treatment response and long-term outcomes. Several biomarkers have shown promise in improving predictive and prognostic precision. Biomarker-guided strategies can identify high-risk patients before extensive target organ damage occurs and low-risk patients who may benefit from lower-intensity treatment, thereby reducing GVHD-related organ injury and adverse effects such as infection and disease relapse. These approaches have facilitated more personalized treatment, with some studies reporting reduced infection rates and improved GVHD-related outcomes in appropriately selected populations. Biomarker-driven clinical trial designs represent a promising framework for developing risk-adapted GVHD management strategies; however, continued validation and refinement of biomarker algorithms is essential to optimize patient outcomes.

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.

Neutropenic patients with hematological malignancies are at high risk for infectious complications. Whether associated lymphopenia or hypogammaglobulinemia further increase this risk and affect outcome remains unclear. This retrospective single-center study included 321 patients hospitalized with lymphoma or leukemia and severe neutropenia whose serum immunoglobulin levels were measured. Overall, 60% of patients had isolated lymphopenia, 9% isolated hypogammaglobulinemia, 24% both, and 7% none. There was no correlation between absolute lymphocyte count and IgG. Severe lymphopenia was not associated with infection or mortality. Hypogammaglobulinemia was more prevalent in lymphoid leukemias and lymphomas. A multivariate logistic regression analysis adjusting for age, underlying hematological malignancy, absolute neutrophil and lymphocyte counts, and duration of neutropenia and lymphopenia showed that hypogammaglobulinemia was associated with infection (OR 1.85, 95% CI 1.07-3.26, p = 0.03), pneumonia (OR 2.04, 95% CI 1.13-3.72, p = 0.02), and sepsis or septic shock (OR 2.43, 95% CI 1.26-4.72, p = 0.01). This indicates a need for further investigation into the role of immunoglobulin replacement therapy in this setting.