International Journal of Hematology最新文献

Iron absorption after the administration of oral iron preparations following a meal is generally reduced compared with fasting. The aim of this study was to investigate the effect of food on iron absorption following ferric citrate hydrate administration in patients with iron deficiency anemia. A randomized, open-label, two-cohort, two-period, single-dose crossover study was conducted to assess the effect of food on iron absorption when 500 mg ferric citrate hydrate (approximately 120 mg of ferric iron) was administered under fasted and fed (immediately after a meal) conditions. Twelve patients aged 20-45 years with iron deficiency anemia (hemoglobin: male 8.0-13.0 g/dL, female 8.0-12.0 g/dL; serum ferritin < 12 ng/mL; transferrin saturation ≤ 16%), participated. The maximum serum iron concentration change was defined as ΔC_max, and the area under the serum iron concentration change versus time curve from baseline to 24 h after administration as ΔAUC_0-24. Serum iron levels increased regardless of fasting or fed conditions, and the ΔC_max and ΔAUC_0-24 values were 39% and 29% higher, respectively, under fed versus fasting conditions. No adverse events were reported. In conclusion, food had no notable effect on iron absorption following ferric citrate hydrate administration in patients with iron deficiency anemia.

Quizartinib is an oral, once-daily, highly potent and selective second-generation, type II FMS-like tyrosine kinase 3 (FLT3) inhibitor, approved for the treatment of newly diagnosed and relapsed/refractory (R/R) FLT3-internal tandem duplication (ITD)-positive acute myeloid leukemia (AML). This descriptive, observational post-marketing surveillance (PMS) investigated the safety of quizartinib in patients with R/R FLT3-ITD-positive AML who initiated quizartinib between October 2019 and December 2021 in Japan. The safety analysis dataset included 126 patients (mean age 60.4 years) who consented to data publication. Eighty patients (63.5%) had previously received another FLT3 inhibitor. The median treatment duration was 71.0 days. Adverse drug reactions (ADRs) occurred in 68 patients (54.0%); grade ≥ 3 and serious ADRs occurred in 44 (34.9%) and 20 (15.9%) patients, respectively. QT interval prolongation occurred in 18/124 patients (14.5%), and the first event typically occurred < 30 days, but sometimes ≥ 150 days, after quizartinib initiation; none of these patients experienced clinical symptoms associated with the ADR. This PMS showed that the safety profile of quizartinib in routine clinical practice in Japanese patients with R/R FLT3-ITD-positive AML did not differ from the known safety profile of quizartinib. QT interval prolongation was manageable with current risk minimization measures.

Background: Massive gastrointestinal (GI), intraperitoneal, and pelvic hemorrhage in inherited bleeding disorders (IBDs) is rare but potentially life-threatening. Pediatric data remain limited.

Methods: We retrospectively reviewed patients ≤ 18 years with hemophilia A/B, von Willebrand disease (VWD), or rare bleeding disorders admitted with massive abdominal hemorrhage (September 2017-August 2025). Massive GI bleeding was defined as overt bleeding with estimated loss > 70 mL/kg/day or bleeding resulting in shock or transfusion. Intraperitoneal and pelvic hemorrhage required imaging confirmation. Demographics, interventions, and outcomes were analyzed and compared with the pediatric IBD cohort.

Results: Of 788 pediatric IBD patients, 10 (1.2%) developed massive abdominal hemorrhage: GI (n = 5), intraperitoneal (n = 3), and pelvic hematoma (n = 2). The GI bleeding cohort was older than the pediatric IBD cohort (median 16 vs. 8 years, p < 0.001). Diagnoses included hemophilia A (n = 4; 75% inhibitor-positive), hemophilia B (n = 1), VWD (n = 4), and Glanzmann thrombasthenia (n = 1). Seven required transfusions; four met massive transfusion criteria. Endoscopy identified a bleeding source in 80% of GI bleeds. Diagnostic delays were longer for intraperitoneal hemorrhage than for GI bleeds (p < 0.05).

Conclusions: Massive abdominal haemorrhage causes significant morbidity. Early imaging, endoscopy, and aggressive hemostatic therapy resulted in 100% survival. Improved access to prophylaxis may prevent such events.

Myeloproliferative neoplasms (MPNs) are clonal hematologic disorders characterized by proliferation of one or more myeloid lineages. Data from large-scale prospective studies in Japan remain limited. We conducted a multicenter, prospective observational study (MPN-15) for the Japanese Society of Hematology to assess clinical characteristics, mutation profiles, risk stratification, and treatment patterns of patients diagnosed with polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic primary myelofibrosis (pre-PMF), and fibrotic PMF after 2016. A total of 1252 patients were enrolled (PV: 323; ET: 726; MF: 203). JAK2V617F mutations were detected in 96.8% of PV patients and approximately 60% of patients with other subtypes; CALR and MPL mutations were more common in ET, pre-PMF, and fibrotic PMF. Chromosomal abnormalities and symptom burden were highest in fibrotic PMF. Thrombotic and survival risk stratification revealed that most patients with PV and ET were high risk. Use of ruxolitinib was reported in 14% of PV and 34% of fibrotic PMF patients, with no serious adverse events. This study represents the first large-scale prospective MPN registry in Japan. Ongoing follow-up will provide critical insights into long-term outcomes and therapeutic optimization in the Japanese population.

Historically, patients with T-cell acute lymphoblastic leukemia (ALL) had poorer outcomes than those with B-cell ALL. However, with intensive chemotherapy regimens, outcomes for both groups have become similar. From 2002 to 2008, the Japan Association of Childhood Leukemia Study (JACLS) conducted the prospective ALL-02 study, using a unique protocol for T-ALL (T-02). All T-ALL patients received the same induction therapy, and those who had < 25% bone marrow blasts at day 15 and achieved complete remission (CR) after induction continued on the T-02 protocol. Of the 107 T-ALL patients enrolled, 98 (91.6%) achieved CR after induction. Among 79 patients continuing on the T-02 protocol, the 2-year event-free survival (EFS), the study's primary outcome, was 70.9%, with a cumulative incidence of relapse of 29.1% and no observed nonrelapse mortality. Univariate analysis identified female sex as a significant predictor of better EFS. This study suggests that excessive treatment reduction may lead to poorer outcomes, although female patients with a rapid early response could potentially benefit from less-intensive therapy, warranting further investigation in a larger study.

Acute and chronic graft-versus-host disease (GVHD) remains major obstacles to the success of allogeneic hematopoietic cell transplantation (allo-HCT). Recent advances in experimental models and clinical studies have refined our understanding of the cellular and molecular mechanisms that drive GVHD and revealed new therapeutic opportunities. Emerging evidence indicates tissue tolerance mediated by epithelial regeneration from tissue stem cells plays a protective role against GVHD. Furthermore, we recently found tissue stem cells persisting after acute GVHD have epigenetic changes that lead to GVHD exacerbation at GVHD flare. Chronic GVHD develops through a more complex immunopathology involving T and B cells, macrophages, and fibroblasts. Disrupted immune reconstitution, including impaired thymic tolerance, aberrant B-cell activation driven by BAFF, and defective regulatory T-cell recovery, contributes to sustained alloimmunity. T-cell exhaustion has recently been recognized as a central checkpoint: While terminal exhaustion promotes tolerance, early calcineurin inhibitor (CNI) administration suppresses terminal exhaustion and drives the accumulation of transitory exhausted T cells that mediate chronic GVHD while preserving graft-versus-leukemia (GVL) activity. Post-transplant cyclophosphamide (PTCy)-based platforms highlight how delayed CNI initiation reduces chronic GVHD by permitting donor T cells to undergo exhaustion.

Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is a rare congenital disorder caused by PRF1 mutations that leads to life-threatening hemophagocytic lymphohistiocytosis during infancy. Hematopoietic cell transplantation (HCT) is the only curative treatment, but optimal transplantation strategies remain unclear. We report two cases of infants with FHL2 successfully treated with cord blood transplantation (CBT) following reduced-intensity conditioning (RIC). Case 1: A 1 month-old boy presented with fever, pancytopenia, and multi-organ failure. Genetic testing identified compound heterozygous PRF1 mutations. After immunochemotherapy, he underwent RIC-CBT at 2 months of age. Engraftment occurred on day 16, complicated by grade II acute graft-versus-host disease (GVHD) and sinusoidal obstruction syndrome, both successfully managed. He remains alive and disease-free 10 years post-transplant with complete donor chimerism. Case 2: A 1 month-old girl presented with fever, respiratory failure, and pancytopenia. She was diagnosed with FHL2 due to a homozygous PRF1 mutation. Following immunochemotherapy, she underwent RIC-CBT at 3 months of age. Engraftment occurred on day 15, without GVHD. She developed remains alive and disease-free 2.5 years later, with stable donor-dominant mixed chimerism (approximately 90%). These cases highlight the feasibility and efficacy of immunochemotherapy followed by RIC-CBT in infants with FHL2.

This study evaluated cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation (allo-SCT) using both CMV-PCR and antigenemia assays in 109 adult recipients. CMV-PCR and antigenemia values had a moderate linear correlation. In total, 58 patients exhibited CMV-PCR positivity before starting antigenemia-based preemptive treatment. Excluding the two patients with persistent PCR positivity, the antigenemia value subsequently reached the threshold in 31 of 54 patients. On the other hand, 25 patients had spontaneous clearance of viremia without preemptive treatment. Spontaneous clearance was associated with letermovir use and the absence of graft-versus-host disease. The clinical course of CMV infection was simulated using various CMV-PCR thresholds (range 50-1000 IU/mL). In high-risk patients not treated with letermovir, a threshold of 50 IU/mL enables preemptive treatment initiation without increasing overtreatment risk in patients with spontaneous clearance. However, in high-risk patients treated with letermovir, thresholds > 150 IU/mL delayed the start of preemptive treatment. In low-risk patients, a threshold of 500-750 IU/mL balances avoiding spontaneous resolution and increasing delayed treatment. PCR thresholds of 50 and 150 IU/mL may be appropriate for initiating preemptive therapy in high-risk patients treated and not treated with letermovir, respectively, while 500-750 IU/mL may be optimal for low-risk patients.

This study aimed to determine the clinical profile and disease burden of patients with paroxysmal nocturnal hemoglobinuria (PNH) in Japan using real-world data from the Adelphi Real World PNH Disease Specific Programme (DSP)™, a cross-sectional survey conducted between January and December 2022. Data included demographics, treatment, and clinical values (hemoglobin [Hb] and lactate dehydrogenase [LDH]). Patient-reported outcome measures included the EQ-5D-5L and the FACIT-Fatigue. Seventeen physicians provided information on 45 patients, among whom 86.7% were receiving treatment with complement 5 inhibitors (C5i). Median (IQR) age was 65.0 (54.5, 73.0) years; 55.6% were male. Among C5i-treated patients (n = 39), 51.3% received ravulizumab and 48.7% eculizumab, for a median (IQR) duration of 1.6 (1.0, 2.7) years. Median (IQR) Hb level was 7.2 (7.0, 8.1) g/dL at diagnosis and 10.0 (8.8, 10.6) g/dL at survey; 91.4% had LDH levels exceeding 1.5 times the upper limit of normal at diagnosis, 11.4% at survey. Twelve patients returned a self-completed questionnaire. Patient-reported symptoms included tiredness (83.3%), shortness of breath (75.0%), and anemia (58.3%). Mean (SD) EQ-5D-5L and FACIT-Fatigue scores were 0.73 (0.16) and 32.3 (7.1). Even C5i-treated patients continued to experience substantial disease burden, highlighting the need for more effective treatments to improve quality of life.