International Journal of Hematology最新文献

Chronic myeloid leukemia (CML) is characterized by the BCR::ABL1 fusion gene, resulting from Philadelphia (Ph) chromosome rearrangements that generate abnormal t (9; 22)(q34;q11) translocations. The most common fusion variants are e13a2 and e14a2. We diagnosed a case of CML with the rare e8a2 fusion variant using real-time quantitative PCR and sequencing. Although the e8a2 variant is increasingly reported in CML, comprehensive retrospective analyses remain scarce. Through a systematic review of published e8a2 BCR::ABL1 cases, we summarized the classification, treatment outcomes, and prognostic characteristics associated with this rare genotype. This analysis aims to provide additional evidence to facilitate improved diagnosis and therapeutic strategies for e8a2-positive CML patients.

Measurable residual disease (MRD), defined as the persistence of minimal levels of leukemic cells following therapeutic intervention, serves as a pivotal prognostic biomarker in patients with chronic lymphocytic leukemia (CLL). We conducted a multicenter, cross-sectional study to assess MRD in Japanese patients with relapsed or refractory CLL. All patients received venetoclax-based therapy for 24 months. MRD in peripheral blood (PB) and bone marrow was assessed by multicolor flow cytometry using surface markers, including kappa and lambda light chains of surface immunoglobulins. The primary and secondary outcomes were the proportions of patients who achieved undetectable MRD (uMRD, < 10^-4 CLL cells) and low-MRD (< 10^-2 and ≥ 10^-4 CLL cells) after 24 months of venetoclax treatment. From June 2023 to December 2024, 60 patients were enrolled, and 51 were analyzed. The median age was 78 years, and 68.6% were male. Thirty-four of 51 patients (66.7%) achieved uMRD, and 8 (15.7%) achieved low-MRD in PB after at least 24 months of venetoclax treatment. Assessment of MRD in PB by flow cytometry is helpful for evaluating treatment response, informing clinical decision-making, and predicting long-term outcomes in clinical practice. Further analyses are warranted to investigate the use of MRD in treatment decision-making and prognostication.Kindly check the inserted city in affiliations 5 and 9.The city names were corrrected.

IMiDs (immunomodulatory drugs from the thalidomide class) enhance hemoglobin F (HbF) production but are not yet approved for sickle cell disease (SCD). Here, we describe a case of severe SCD and multiple myeloma (MM) in which over 6 years of treatment with IMiDs and hydroxyurea led to sustained remission of SCD.

CYCS encodes somatic cytochrome c, which plays a central role in the electron transport chain and oxidative phosphorylation. We report nine cases of autosomal dominant, non-syndromic CYCS-related thrombocytopenia in three Japanese families. Patients showed no or mild bleeding tendency, with preserved platelet size and morphology, and without other abnormalities in blood cell lineages. Using targeted gene sequencing for congenital thrombocytopenia, we identified pathogenic missense variants in CYCS, shared by all affected individuals in each family. Two were previously reported: c.274A > G,p.(Arg92Gly) and c.309C > T,p.(Thr103Ile); one was novel: c.212A > C,p.(Asn71Thr). Genetic testing should be considered in unexplained familial thrombocytopenia.

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.