International Journal of Hematology最新文献

Outbreaks of measles and rubella occasionally occur, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients face an increased risk of mortality from measles. This retrospective observational study assessed immunological responses to MR vaccination and long-term changes in antibody titers in adult allo-HSCT recipients. The measles and rubella cohorts included 36 and 33 patients, respectively, who received MR vaccination between March 2010 and December 2023. MR vaccination significantly increased IgG titers against measles from 5.48 (± 3.61) at T0 (pre-vaccination) to 14.15 (± 10.31) at T1 (1 year post-vaccination) and against rubella from 3.90 (± 2.82) at T0 to 58.93 (± 44.46) at T1 (both p < 0.001). Multivariate analyses in the measles cohort showed that lower IgG antibody titers at T0 were significantly associated with high responder status (OR 0.57, 95% CI 0.35-0.96, p = 0.029). High responders had significant mean changes in IgG antibody titers from T0 to each time point from T1 to T5 (5 years post-vaccination) for both measles and rubella. The annual decline in IgG titers was predicted to be 2.14 (p = 0.002) for measles and 3.15 (p = 0.51) for rubella in high responders. Despite high antibody titers, these levels decline over time, emphasizing the importance of regular monitoring and potential revaccination.

De novo Ph-positive MDS with the micro BCR::ABL1 (e19a2/p230) transcript is rare. Here, we report a case of MDS with multilineage dysplasia in an 86-year-old woman. Reverse transcription polymerase chain reaction (RT-PCR) showed the following karyotype: 46, XX, t(9;22)(q34.1;q11.2), i(17)(q10) [20], and p230 BCR::ABL1. Targeted NGS at diagnosis revealed mutations in CSF3R, BCOR, SRSF2, and ASXL1. Low-dose dasatinib (20 mg/day) reduced BCR::ABL1 levels (FISH negative, RT-PCR positive), but had no effect on anemia, dysplasia, or transfusion frequency. At six months, panel results showed loss of all mutations except ASXL1, as well as clearance of Ph-positive subclones. However, an ASXL1 founder clone persisted. Post-treatment chromosome analysis was not feasible because of poor cell growth. Serial genomics suggested that Ph positivity was a late/secondary event on a pre-existing ASXL1-mutant background. In Ph-positive de novo MDS, BCR::ABL1 transcript responses alone may not reflect disease control when an adverse founder clone persists. Integrating panel-based NGS with fusion transcript monitoring may improve therapeutic decision-making and prognostic assessment.

Arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) has been shown to be effective in both adult and pediatric patients with acute promyelocytic leukemia (APL). Addition of ATO to conventional chemotherapy could lead to a reduction in the doses of cytotoxic agents, but the long-term safety of ATO is not fully understood, especially in children. The Japan Children's Cancer Group conducted a risk-stratified prospective study to investigate safety and efficacy of ATO in children with newly diagnosed APL by replacing all three intensification phases with ATO. The 3-year event-free survival and overall survival rates in 27 children were 96.3% (95% CI 76.5%-99.5%) and 100% (95% CI 87.2%-100%), respectively. Prolonged QTc interval or other cardiac conduction disorders of any grade were observed in 20 out of the 63 intensification cycles. The durations of leukocytopenia, neutropenia, and G-CSF treatment were significantly shorter in this study than in a previous Japanese study that used conventional cytotoxic chemotherapy. Furthermore, no cardiac, metabolic, renal, cutaneous, or neurological symptoms were reported for up to 5 years after completion of the protocol therapy. The JPLSG AML-P13 study demonstrated excellent outcomes and safety of ATO in children with APL.

Immune checkpoint inhibitors (CPIs) targeting PD-1, such as nivolumab and pembrolizumab, have become integral to the treatment of relapsed or refractory classical Hodgkin lymphoma (cHL), frequently serving as a bridge to autologous stem cell transplantation (ASCT). However, recent reports suggest that CPI exposure prior to ASCT may increase the risk of engraftment syndrome (ES), an inflammatory complication that emerges during neutrophil recovery. We present three cases of cHL treated by ASCT was performed following anti PD-1-based salvage therapy. Two of the three patients developed ES, with one case requiring high-dose corticosteroid pulse therapy due to severe respiratory symptoms. We examined lymphocyte counts and the interval between the final CPI dose and transplantation as potential contributing factors. While lymphocyte counts did not correlate with ES severity, the patient with the highest ES severity had the shortest CPI-to-transplant interval. These findings suggest that recent CPI exposure may contribute to ES, possibly via prolonged immune activation. As CPIs become more widely used in pre-ASCT regimens, clinicians should remain alert to the potential for delayed inflammatory toxicities and consider the timing of transplantation when planning post-CPI management strategies.

Objective: Central nervous system (CNS) prophylaxis is recommended for patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk of CNS relapse. This study aimed to determine the impact of CNS prophylaxis on CNS relapse rates and overall survival (OS) in this patient population, as well as the optimal method for CNS prophylaxis.

Methods: This was a retrospective analysis of 178 patients with DLBCL at high risk of CNS relapse who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) or its derivatives with (N = 60) or without (N = 118) CNS prophylaxis.

Results: The 2-year CNS relapse rate was 17.6% in the all-prophylaxis group (HD-MTX 17.4%, IT 48.1%, and HD-MTX + IT 6.2%) and 13.0% in the non-prophylaxis group, with no significant difference between groups. However, HD-MTX + IT decreased the risk of CNS relapse. After a median follow-up of 72.8 months, HD-MTX + IT addition significantly improved the 5-year OS (HD-MTX 73.5%, IT 44.4%, HD-MTX + IT 93.2%; non-prophylaxis group 58.0%; p = 0.013). This advantage was maintained in the multivariate analysis (hazard ratio: 0.160; 95% confidence interval: 0.039-0.663; p = 0.012).

Conclusions: CNS prophylaxis with HD-MTX + IT improved the prognosis of patients with DLBCL at high risk of CNS relapse.

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.