International Journal of Hematology最新文献

Cytogenetic abnormalities are associated with poor prognosis in systemic light chain (AL) amyloidosis, but evidence on treatment options that might overcome this adverse impact remains limited. In this study, we investigated whether the combination of bortezomib and autologous stem cell transplantation (ASCT) could overcome the adverse prognosis of AL amyloidosis with cytogenetic abnormalities. The study included 134 patients. The 52 patients treated with a bortezomib-based regimen and ASCT were defined as Group A, and the 82 patients who received a bortezomib-based regimen without ASCT were defined as Group B. Cytogenetic abnormalities were present in 73 patients, and included IgH rearrangement (71.2%), + 1q21 (46.6%), del13q (37%), and del17p (6.8%). Hematological response and overall survival (OS) were better in Group A than in Group B, especially among patients with cytogenetic abnormalities. Within Group A, there was no difference in hematological response, progression-free survival (PFS), or OS between patients with and without cytogenetic abnormalities. Within Group B, IgH rearrangement was associated with inferior hematological response and OS. In conclusion, our study demonstrated that a bortezomib-based regimen combined with ASCT can overcome the adverse prognosis of AL amyloidosis with cytogenetic abnormalities.

Background: In Japan, multiagent chemotherapy comprising anthracycline and cytarabine is commonly used as post-remission consolidation therapy for acute myeloid leukemia. Meanwhile, intermediate-dose cytarabine (ID-AC) is typically utilized in Western countries. However, data comparing these two regimens are limited. The current study retrospectively analyzed the outcomes of multiagent chemotherapy and ID-AC as consolidation therapy in patients at our institution.

Methods: Seventy-one patients were included in the multiagent chemotherapy group and 46 in the ID-AC group.

Results: Two-year overall survival rates did not differ significantly between the multiagent chemotherapy and ID-AC groups (56.0% vs. 69.2%; P = 0.169). Similarly, 2-year disease-free survival with data censored at the time of allogeneic stem cell transplantation did not significantly differ between groups (14.1% vs. 33.5%; P = 0.268). The ID-AC group had a significantly lower incidence of febrile neutropenia than the multiagent chemotherapy group. Further, the ID-AC group had a significantly shorter duration of neutropenia and length of hospital stay than the multiagent chemotherapy group.

Conclusion: ID-AC had comparable efficacy and a more favorable safety profile than multiagent chemotherapy as consolidation therapy for acute myeloid leukemia.

Background: Relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) exhibits substantial clinical heterogeneity, with different outcomes based on disease burden and anatomical distribution. However, the prognostic implications of multi-site involvement at first R/R remain unclear.

Methods: We retrospectively analyzed data from 81 patients with DLBCL who experienced first R/R after initial treatment at our institution. We assessed clinical variables at first R/R-including involved sites and disease dissemination patterns, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group performance status (ECOG PS)-for associations with progression-free survival (PFS) and overall survival (OS).

Results: Multi-site involvement (≥ 2 sites) at first R/R was significantly associated with shorter PFS and OS, independent of nodal or extranodal status. In multivariable analysis, multi-site involvement at first R/R remained a strong prognostic factor for both PFS and OS, along with IPI at first R/R for PFS, and ECOG PS > 1, elevated LDH, and age > 80 years for OS. None of these relapse-specific prognostic factors were significant at initial diagnosis.

Conclusion: Multi-site disease at first R/R represents an adverse prognostic feature in DLBCL. These findings underscore the importance of considering disease distribution when evaluating prognosis and planning treatment strategies for R/R cases.

Objective: To verify the clinical benefit of ropeginterferon alfa-2b (ropegIFN) and evaluate its cost-effectiveness compared with hydroxycarbamide or ruxolitinib for patients with polycythemia vera (PV) under the National Health Insurance (NHI) system in Japan.

Methods: The cost-effectiveness of ropegIFN compared with hydroxycarbamide or ruxolitinib was evaluated for patients with PV requiring cytoreductive therapy (without prior cytoreductive therapy) and resistant or intolerant to hydroxycarbamide. According to previous reports, patients with PV who achieve a molecular response with a JAK2V617F allele burden < 10% tend to maintain hematologic responses even after discontinuing interferon treatment. Therefore, in these analyses, patients who achieved a molecular response with JAK2V617F burden < 10% discontinued ropegIFN treatment.

Results: Compared with hydroxycarbamide, ropegIFN yielded an incremental effectiveness of 0.440 quality-adjusted life years (QALYs), indicating a higher QALY gain. The incremental costs were 128,001,730 yen, and the incremental cost-effectiveness ratio (ICER) was 291,092,030 yen/QALY. Compared with ruxolitinib, the incremental effectiveness of ropegIFN was 1.278 QALYs, while the total costs were reduced by 18,025,182 yen, which resulted in a dominant ICER.

Conclusions: These results suggest that ropegIFN may be cost-effective compared with ruxolitinib in patients with PV who are resistant or intolerant to hydroxycarbamide under the NHI system in Japan.

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.

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.