International Journal of Hematology最新文献

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.

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.

Purpose: This study investigated the correlation between plasma biomarker levels and post-transplant complications of allo-HSCT in children. The biomarkers analyzed were sST2, REG3α, TNFR1, IL-6, and IL-8.

Methods: From January 1, 2019 to October 30, 2024, specimens from 157 patients were collected at aGVHD onset or when aGVHD was clinically presumed to be likely to occur.

Results: Patients with aGVHD and intestinal aGVHD had significantly elevated sST2 levels. Patients with grade III/IV aGVHD had significantly higher sST2 and REG3α levels than patients with grade I/II aGVHD. OS and NRM differed significantly between patients with high sST2 and REG3α indexes (sST2 ≥ 124,090 pg/ml and REG3α ≥ 17,176 pg/ml) and those with low sST2 and REG3α indexes (P < 0.05). Univariate logistic regression analysis indicated that aGVHD, SOS, and TA-TMA were correlated with elevated sST2 and REG3α levels. Multivariate logistic regression analysis indicated that grade III/IV aGVHD was significantly associated with elevated sST2 and REG3α levels (each P = 0.003).

Conclusions: Elevated sST2 and REG3α can reflect the occurrence and severity of aGVHD. Acute GVHD, SOS, and TA-TMA can all lead to fluctuations in sST2 and REG3α levels, and warrant further study.

Although several studies suggest that higher busulfan exposure is associated with neurotoxicity, research on the relevance of pharmacokinetic parameters is limited. The aim of this study was to explore the impact of busulfan area under the concentration-time curve (AUC) on the development of neurological complications in children and adolescents receiving busulfan-containing conditioning regimens. Patients aged 0-20 years who received a busulfan-based regimen at our hospital between June 2017 and May 2024 were analyzed. The primary outcome measure was the incidence of neurological complications within 7 days of starting busulfan. A total of 36 consecutive patients were analyzed. Median busulfan AUC across 96 h (AUC96) was 86.3 (interquartile range 73.6-100.8) mg × h/L. Overall, 13 (36%) patients developed neurological complications, including 2 patients with grade 3 seizures. The AUC96 cut-off value was set at 80.0 mg × h/L (sensitivity 85%, specificity 57%, area under the receiver-operating characteristic curve 0.71). A higher incidence of neurological complications was observed in the AUC96 > 80.0 mg × h/L group than in the AUC96 ≤ 80.0 mg × h/L group (50% vs. 14%, P = 0.033). These results suggest that a higher busulfan AUC96 may be associated with an increased risk of neurological complications.

Background: Hearing loss is a recognized permanent consequence (PC) of Langerhans cell histiocytosis (LCH). However, its characteristics and association with central nervous system (CNS)-related PCs remain unclear.

Procedure: This study retrospectively analyzed the data of 317 pediatric patients with multisystem or multifocal bone LCH enrolled in the Japan LCH Study Group -96 or -02 trial.

Results: Hearing loss was identified in nine patients (2.8%), a lower incidence than previously reported. It was significantly associated with ear lesions, but not with craniofacial bone involvement at the time of diagnosis. Detailed information was available for seven patients: Three had sensorineural hearing loss, and four had mixed-type hearing loss without hearing improvement. At the last follow-up, hearing loss was unilateral in six cases and bilateral in one, with severity ranging from moderate (n = 1) to severe (n = 2) and profound (n = 4). CNS-PCs were found in five patients and were significantly associated with hearing loss (p = 0.018). One patient without ear lesions developed progressive sensorineural hearing loss due to neurodegeneration (ND).

Conclusions: Patients with hearing loss should be closely monitored for CNS-PCs, and those with LCH-associated ND should be carefully monitored for the development of sensorineural hearing loss.

TAFRO syndrome is a rare systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. Its pathogenesis remains elusive, and its non-specific symptoms overlap with idiopathic multicentric Castleman disease, complicating its management. This report discusses two cases of TAFRO syndrome resistant to conventional treatments, including corticosteroids, tocilizumab, and rituximab. Both patients showed significant clinical improvement after treatment with ruxolitinib, a JAK-STAT pathway inhibitor. The first patient was a 55-year-old man who showed clinical improvement with ruxolitinib after the failure of multiple lines of treatment, including corticosteroids, tocilizumab, rituximab, and cyclosporin A. The second was another 55-year-old man who experienced disease relapse 18 months after initial treatment but responded rapidly to ruxolitinib. These cases highlight the potential role of ruxolitinib as a therapeutic option for refractory TAFRO syndrome. In addition, Epstein-Barr virus (EBV) DNA was detected in the serum of the first patient, making this the first report to demonstrate the effectiveness of ruxolitinib in EBV-associated TAFRO syndrome. These findings highlight the need for further studies to confirm the efficacy of ruxolitinib in such cases and elucidate the pathophysiological mechanisms underlying TAFRO syndrome, which could guide future therapeutic strategies.

Background: The CD3xCD20 bispecific antibody epcoritamab demonstrated deep, durable responses with manageable safety in relapsed/refractory (R/R) follicular lymphoma (FL) in EPCORE NHL-3 (phase 1/2; NCT04542824). This analysis evaluated 3-year follow-up outcomes in Japanese patients.

Methods: Adults with CD20 + FL and ≥ 2 prior lines of therapy (LOTs) received subcutaneous epcoritamab (0.16/0.8-mg step-up doses; 48-mg full doses) until disease progression or death. The primary endpoint was overall response rate (ORR).

Results: Twenty-one patients received epcoritamab (median age: 65 years; median prior LOTs: 4; 57.1% double refractory; 57.1% progressed within 24 months of any first-line treatment). At a median follow-up of 35 months, the ORR was 95.2% and the complete response (CR) rate was 76.2%. Median duration of response, duration of CR, progression-free survival, and overall survival were not reached. At 3 years, 66.7% and 93.3% of complete responders remained progression-free and alive, respectively. Minimal residual disease negativity was achieved in 88.9% (16/18) of evaluable patients. Common treatment-emergent adverse events included cytokine release syndrome (90.5%) and injection-site reaction (71.4%), all predominantly grade 1-2 and occurring in early treatment cycles, and none fatal.

Conclusions: Epcoritamab monotherapy provided durable long-term remission with favorable safety in Japanese patients with R/R FL over 3 years of follow-up.