International Journal of Hematology最新文献

The epidemiology and clinical characteristics of familial myelodysplastic syndromes/acute myeloid leukemia (MDS/AML) remain poorly understood, particularly among Native Hawaiians and other Pacific Islanders (NHOPI). To investigate the real-world evidence in this area, we conducted a retrospective study at the Queen's Medical Center, Hawaii's largest tertiary referral hospital. This study is based solely on self-reported family histories and interviews, without germline genetic validation. Among 1686 MDS/AML patients who presented between January 2012 and July 2023, 12 (0.71%) had familial MDS/AML and 25 (1.48%) had a family history of unspecified leukemia. While no NHOPI were identified among patients with familial MDS/AML, 20% of patients with a family history of unspecified leukemia were NHOPI. The median age at diagnosis of familial MDS/AML was 70 years, and 50% of familial MDS patients had MDS with low blasts based on the WHO 2022 classification. The median overall survival (OS) time and 5-year OS rate for familial MDS were 12.7 years and 75.0%, respectively. In contrast, familial AML had a median OS time of 0.85 years and a 3-year OS rate of 33.3%. Our study provides new insights into familial MDS/AML in Hawaii's multiethnic population.

The epidemiology of febrile neutropenia (FN) remains poorly understood. Although the Diagnosis Procedure Combination (DPC) database offers valuable clinical information, it lacks FN-specific diagnostic codes. This study aimed to develop an algorithm to identify patients with FN using DPC data and to investigate the epidemiology of FN. Data from St. Luke's International Hospital were used to identify DPC-based FN cases in patients with hematological malignancies who underwent chemotherapy, blood culture collection, and antipseudomonal antibiotic therapy. True FN cases were confirmed through chart review, incorporating neutrophil counts and body temperature. The algorithm demonstrated a sensitivity of 79.6%, specificity of 94.1%, PPV of 81.9%, NPV of 93.2%, and an F-measure of 80.6%. A sensitivity analysis for 2015-2020 showed improved performance: sensitivity 98.9%, specificity 99.6%, PPV 82.4%, NPV 99.6%, and F-measure 89.9%. Among the 144,009 patients with hematological malignancies in the DPC database, 50,558 received chemotherapy, and 13,720 (27.1%) developed FN as indicated by the algorithm, with in-hospital mortality rates of 15.0%. Although 76.7% of patients with FN received guideline-recommended first-line antibiotics, 17.0% received carbapenem, suggesting a potential need for antimicrobial stewardship interventions. The algorithm represents a valuable tool for large-scale epidemiological studies and could help inform strategies for FN management in Japan.

Adult T-cell leukemia-lymphoma (ATL) is one of the most intractable peripheral T-cell neoplasms caused by human T-cell leukemia virus type I (HTLV-1) infection. Recently, the incidence of HTLV-1 infection and ATL has increased in non-endemic metropolitan areas in Japan. This retrospective study evaluated the clinical features and outcomes of patients with aggressive ATL aged 70 years or younger treated at a core hospital in Tokyo between 2004 and 2016. The median follow-up was 124.4 months for survivors. Among the 71 patients, 46 (64.8%) underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). The 3 year overall survival rate was 45.7% in allo-HSCT group versus 0% in non-allo-HSCT group. Patients who achieved complete/partial remission before allo-HSCT had a significantly better survival rate than those with stable/progressive disease (51.4% vs 27.3%). The 2 year cumulative incidence of relapse/progression and non-relapse mortality after allo-HSCT was 41.3% and 21.7%, respectively. In this study, a large percentage of patients underwent allo-HSCT and achieved favorable outcomes. As cases continue to rise in metropolitan areas, core hospitals will play a critical role in ATL treatment.

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.