International Journal of Hematology最新文献

Because primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) is rare, key clinical questions, including the best treatment strategy and the validity of watchful waiting (WW), remain unresolved. Although radiotherapy (RT) is the standard treatment for localized POAML, it is commonly associated with acute and late toxicities. Overall, 128 patients with localized POAML diagnosed and managed at our institution between 1998 and 2015 were retrospectively analyzed. Forty-two patients were initially managed with WW, and 86 received immediate RT. During a median follow-up of 7.2 years (range 0.1-18.4), no patients died of lymphoma progression. Seven patients in the WW group experienced disease progression at the primary site. In the RT group, almost all patients (97.7%) achieved a complete response after RT; however, 12 patients relapsed. Histological transformation occurred in one patient in each group. The 10-year cumulative incidence of progression was 24.9% (95% CI, 12.6-45.7%) with WW and 13.1% (95% CI, 6.9-23.9%) with RT (p = 0.27). The rate of freedom from systemic therapy at 10 years was 89.7 and 94.8%, respectively (p = 0.67). This observational study suggests that WW is an acceptable treatment option for selected patients with localized POAML, with no significant differences in long-term outcomes compared with RT.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-dependent intravascular hemolysis and thrombosis as well as bone marrow failure. Complement dysregulation occurs as a result of defective cell surface expression of two glycosylphosphatidylinositol (GPI)-anchored complement regulators, decay-accelerating factor/CD55 and CD59, caused by somatic mutation of the phosphatidylinositol glycan anchor biosynthesis class A gene (PIGA). Somatic loss-of-function mutation of PIGA generates GPI-anchor-defective hematopoietic stem cell clones, the expansion of which results in large numbers of abnormal erythrocytes, platelets, and other blood cells. The clonal expansion of PIGA mutant hematopoietic stem cells is thought to be mediated by an autoimmune mechanism that suppresses or eliminates normal hematopoietic stem cells while sparing GPI-defective stem cell clones under bone marrow failure environments, the acquisition of a growth phenotype, or both of these mechanisms. This review examines current knowledge and views about the clonal expansion mechanism.

Graft-versus-host disease (GVHD) remains a major barrier to successful allogeneic hematopoietic stem cell transplantation, and its prevention requires not only suppression of early alloimmune responses but also the rational design of post-transplant immune reconstitution. The pathophysiology of GVHD has traditionally been understood based on Billingham's classical three criteria and a subsequent cytokine storm-driven, multistep model that emphasizes early tissue injury. In recent years, however, emerging concepts-including disruption of tissue tolerance in target organs and the layered reconstitution of donor T cells after transplantation, characterized by dynamic changes in fitness and exhaustion-have led to a refinement of these classical frameworks. This review summarizes recent advances, focusing on two key aspects: (1) updated local pathophysiological mechanisms, including injury to tissue stem cells and impaired regenerative capacity in target organs, disruption of the gut microbiota-metabolic network, and damage to the bone marrow hematopoietic niche; and (2) the mechanistic links between immune reconstitution and the development of acute and chronic GVHD, based on recent studies of donor T cell clonal dynamics. These insights support a shift from a unidimensional, immunosuppression-centered approach toward a novel, multidimensional therapeutic strategy that integrates organ protection, hematopoietic niche repair, and precise control of immune reconstitution.

Tumor-associated bronchiolitis obliterans (BO) is a major cause of death and is frequently complicated by paraneoplastic pemphigoid (PNP). In this study, three cases of follicular lymphoma (FL) with BO were retrospectively analyzed. All cases were complicated by PNP. All patients achieved a tumor response with anti-CD20 monoclonal antibody-containing treatment, and two patients showed clinical improvement in PNP. However, BO continued to progress, and two of the three patients developed pulmonary infections.

Relapsed/refractory multiple myeloma (RRMM) with extramedullary disease (EMD) is associated with poor prognosis and limited response to standard therapies. Elranatamab, a bispecific antibody targeting BCMA and CD3, has demonstrated clinical activity in triple-class-exposed (TCE) RRMM but remains less effective in patients with EMD. We report a case of a 67-year-old woman with TCE RRMM and aggressive EMD that progressed after two cycles of elranatamab. Following the addition of Juzentaihoto (JTT), a traditional Japanese herbal medicine, rapid symptom improvement, tumor regression, and disappearance of M-protein on immunofixation were observed. Moreover, after JTT initiation, lymphocyte and CD4-CD8bright cell counts increased rapidly and robustly, suggesting that JTT may enhance the elranatamab-induced antitumor immune response via these cells. To our knowledge, this is the first in vivo report indicating that JTT increases CD4-CD8bright lymphocyte counts in humans. JTT may enhance the efficacy of T cell-redirecting immunotherapies in RRMM by promoting cytotoxic T cell expansion. These findings warrant further investigation into the use of JTT as an adjunct to improve outcomes in patients with EMD.

Although novel therapeutic agents, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, have markedly improved outcomes in multiple myeloma (MM), the disease remains incurable and is associated with various causes of death. However, comprehensive analyses of mortality patterns, particularly early mortality, are still limited. In this study, we focused on patients who died within one year of treatment initiation (1-year group), based on data from the J-CHARGE-MM database showing that 146 out of 461 total deaths (31.7%) occurred within the first year. The most common cause of death was disease progression (43.2%), followed by infection (primarily pneumonia and sepsis), which frequently occurred within the first few months of induction therapy. Cardiac-associated events, such as heart failure and cardiac amyloidosis (including suspected cases), accounted for 14.4% of deaths, and sudden death for 7.5%. Multivariate analysis revealed that early mortality was significantly associated with age ≥ 65 years, elevated serum lactate dehydrogenase (LDH), elevated serum C-reactive protein (CRP), and poor performance status (PS ≥ 3), compared with later deaths. These findings support that early mortality in MM may be reduced through comprehensive cardiac evaluation and proactive infection prevention strategies, particularly in elderly patients with elevated CRP, elevated LDH, or poor PS.

Introduction: The real-world data on treatment and outcome of hemophilia patients using extended half-life products in developing countries remain scarce. This is largely due to delayed diagnosis, poor joint outcomes, increased morbidity, and limited access to prophylaxis and newer products for treatment and prevention.

Aim: To analyze the response to extended half-life factor (EHL) prophylaxis in patients with severe hemophilia A and B with advanced arthropathy.

Methods: Patients with severe hemophilia A and B who received EHL factor concentrates for prophylaxis at our center were included in this analysis. Data collected included bleed frequency, joint involvement, annualized bleed rate (ABR), number of hospital visits, and Hemophilia Joint Health Score (HJHS) prior to prophylaxis. Breakthrough bleeds while on prophylaxis were also recorded.

Results: A total of 31 patients were started on EHL prophylaxis and followed up for a period ranging from 4 to 91 weeks. A reduction in the bleeding rate was noticed in all with significant reversal of target joints. Additionally, patients remained bleed-free during rehabilitation following joint surgery as well as psoas bleed-related compression neuropathy.

Conclusion: EHL prophylaxis appears to be an effective strategy even for patients with baseline target joints with significant arthropathy, thus reducing the extent of disability in these patients.

Background: Extramedullary plasmacytoma is a rare tumor, that primarily occurs in the head and neck region. We report a case series on head and neck extramedullary plasmacytoma treated with radiation therapy to provide insights regarding clinical outcomes.

Materials and methods: This was a retrospective study on radiation therapy outcomes in patients with head and neck extramedullary plasmacytoma treated between January 2010 and December 2024. The treatment course was evaluated, in terms of local tumor control rates and treatment-related toxicities.

Results: A total of 200 plasmacytoma patients were screened, and 6 patients with extramedullary disease were included in the study. The most common site of occurrence was the larynx. Radiation therapy was administered at a dose of 45-50 Gy in 20-25 fractions. At a mean follow-up of 8 years, overall survival and disease-free survival were 8 and 7 years, respectively. A local control rate of 83% was achieved through radiation therapy alone. One of six patients progressed to multiple myeloma at 3 months; and all patients were alive as of the last follow-up.

Conclusion: In head and neck extramedullary plasmacytoma, radiation offers excellent local control with acceptable toxicities while also preserving organ function.

Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) has a poor prognosis, particularly in patients ineligible for autologous stem cell transplantation or cellular immunotherapy. This study evaluated the effectiveness of polatuzumab vedotin combined with rituximab and bendamustine (PBR) therapy in comparison to conventional chemotherapy in patients with R/R DLBCL. Of 86 patients with first relapse or primary refractory DLBCL, 32 received PBR in any subsequent line, while 54 received conventional chemotherapy alone. For comparison, 32 baseline-matched patients were selected from these 54 and defined as the conventional chemotherapy group. The median overall survival (OS) for all patients was 17.3 months (range, 1.5-85.7 months), with the PBR-treated group showing significantly improved outcomes (median OS 19.7 vs. 15.8 months, P = 0.025). Univariate and multivariate analyses identified PBR as a favorable prognostic factor for OS. In the second-line setting, 41.2% of patients who received PBR were ≥ 80 years, compared with just 11.1% of those who received salvage regimens. Despite this older age distribution, the PBR group showed a trend toward favorable progression-free survival. These results suggest that PBR therapy is more effective and tolerable than conventional chemotherapy in patients with R/R DLBCL.