International Journal of Hematology最新文献

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.

Multiple myeloma is an incurable plasma cell malignancy. Its prognosis improved with the introduction of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, but outcomes for triple-class-exposed (TCE) myeloma remained poor. New therapeutic options including CAR-T cell therapy and bispecific antibodies have now further improved prognosis, even in TCE myeloma. While true cure remains challenging, functional cure, defined as long-term disease control through a favorable immune environment suppressing minimal residual disease (MRD), is currently considered a realistic therapeutic goal.

The diagnosis-to-treatment interval (DTI) has been identified as a prognostic factor in newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, its significance in relapsed or refractory DLBCL (R/R DLBCL) remains unclear. This study aimed to investigate the impact of DTI on survival outcomes in patients with R/R DLBCL. We reviewed the medical records of patients with R/R DLBCL who received second-line therapy. DTI at relapse or refractory disease (r/r DTI) was defined as the time from radiological diagnosis-to-treatment initiation, with a cut-off of 28 days. The primary endpoint was overall survival (OS). A total of 184 patients with R/R DLBCL were included. Patients with short r/r DTI had significantly worse OS than those with long r/r DTI (1-year OS: 50.4% vs. 79.5%; P < 0.001). Short r/r DTI was associated with adverse clinical features, including poor performance status, elevated lactate dehydrogenase levels, and high International Prognostic Index at relapse. Multivariate analysis demonstrated that short r/r DTI was independently associated with significantly inferior OS (HR 1.77; P = 0.043). In conclusion, DTI is an independent prognostic factor in R/R DLBCL and can be considered in patient selection for clinical trials.

Micafungin and other echinocandins are commonly used for the prophylaxis and empirical treatment of invasive fungal infections in neutropenic patients due to their broad-spectrum activity and favorable safety profile. Drug-induced hemolytic anemia (DIHA) is a rare condition, and micafungin-related cases are exceptionally uncommon. We describe a fatal case of intravascular hemolysis triggered by re-administration of micafungin in a patient receiving chemotherapy for peripheral T cell lymphoma. The patient experienced convulsions and shock within minutes of infusion of the drug, followed by severe hemolysis and disseminated intravascular coagulation. Subsequently, hemolytic mechanisms were evaluated using drug-adsorption and immune complex models. Additionally, we had sera from eight patients treated with micafungin between January 2019 and December 2022, including our index case, tested for anti-micafungin antibodies. Immune complex-mediated hemolysis was confirmed in the index case, supported by positive indirect antiglobulin tests and in vitro hemolysis. Anti-micafungin antibodies were only detected in this single patient, indicating an extremely rare immunologic reaction. Although rare, micafungin-induced DIHA can be life-threatening. Clinicians should remain vigilant, particularly when resuming or continuing administration of micafungin.

Peripheral T cell lymphomas (PTCLs) are a heterogeneous group of aggressive lymphomas with generally poor outcomes. CHOP or CHOP-like regimens have long been the standard frontline therapy; however, the addition of brentuximab vedotin has improved overall survival and established a new standard of care for CD30-positive PTCL. Despite this advance, the outcomes of relapsed or refractory (R/R) disease remain dismal. In recent years, multiple novel agents have been developed for the treatment of PTCL, particularly for R/R settings. Molecular profiling has refined disease classifications, identifying subtypes such as nodal T follicular helper (TFH) lymphoma, PTCL-GATA3, and PTCL-TBX21, which differ in their pathogenesis, prognosis, and potential therapeutic vulnerabilities. Epigenetic modulators, including histone deacetylase inhibitors and an EZH1/2 inhibitor, have demonstrated particularly high activity in TFH-derived subtypes, supporting the integration of biomarker-driven patient selection as a path toward precision medicine in PTCL. This review summarizes current insights into the genetic landscape, recent clinical advances in novel agents, and future perspectives on therapeutic stratification, highlighting the need to translate molecular insights into durable clinical benefits for patients with PTCL.

Purpose: Although Hodgkin and non-Hodgkin lymphoma are chemosensitive, 10-15% of patients develop refractory disease. With the increasing use of intensive chemotherapy, the role of radiotherapy (RT) in salvage settings has diminished. This study evaluated the efficacy of salvage RT in patients with refractory lymphoma.

Materials and methods: Forty-one adults with histologically confirmed Hodgkin or non-Hodgkin lymphoma and either primary refractory or relapsed/refractory disease treated between 2010 and 2022 were retrospectively analyzed. All patients received involved-site RT after systemic therapy.

Results: At a median follow-up of 67 months, 85% of patients showed a complete response to salvage RT and 10% showed a partial response. The 5- and 10-year disease-specific survival rates were 90 and 84%. All recurrences occurred within 5 years and outside the RT field.

Conclusion: Salvage RT achieved high response rates, durable survival, and minimal toxicity, supporting its role as a valuable treatment option in selected patients.