Annals of Hematology最新文献

Eltrombopag (ELT) is a second-line therapy for pediatric immune thrombocytopenia (ITP), but inter-individual variability in metabolism leads to wide plasma concentration differences at the same dose, affecting efficacy and adverse drug reactions (ADRs). To validate the feasibility of individualized drug regimens based on blood drug concentration guidance in pediatric persistent/chronic ITP (P/CITP) and to provide a new method of individualized treatment with eltrombopag for pediatric P/CITP. This prospective, observational cohort study enrolled 70 children with refractory persistent/chronic ITP (P/CITP) to evaluate the feasibility and value of plasma concentration–guided individualized dosing. Patients were assigned to a conventional group (dose titration by platelet counts and bleeding events) or an individualized group (dose adjustments additionally guided by ELT concentrations), with 6-month follow-up. Although no statistical significance was observed, the individualized group achieved a higher overall response rate (82.9% vs. 71.4%) and complete response rate (65.7% vs. 48.6%), with more stable platelet counts, fewer bleeding events, reduced requirements for concomitant/rescue therapy, and a lower incidence of ADRs (17.1% vs. 37.1%). Similarly, though not statistically significant, the individualized group had lower direct medical costs and improved cost-effectiveness. These findings suggest that plasma concentration-guided individualized ELT therapy may enhance therapeutic efficacy, improve safety profiles, and reduce medical costs, which represents a meaningful step toward precision medicine in the field of pediatric hematology.

Innate immune cells are emerging as powerful allies in the fight against blood cancers. Natural Killer (NK) cells, macrophages, and dendritic cells (DCs)—once viewed mainly as supporting players—are now at the forefront of next-generation immunotherapies, owing to their rapid, antigen-independent tumor recognition and potent effector functions. This review highlights their distinct anti-tumor roles: NK cells’ cytotoxicity and “missing-self” recognition, the dual and adaptable nature of macrophages in the tumor microenvironment (TME), and the antigen-presenting capabilities of DCs that bridge innate and adaptive immunity. We further examine transformative therapeutic strategies, including adoptive NK cell transfer, CAR-engineered NK cells (CAR-NK), CAR-macrophages (CAR-M), and DC vaccines, with a focus on clinical outcomes and safety—particularly the encouraging toxicity profile of CAR-NK cells. Despite these advances, major challenges persist, including limited persistence and homing of infused cells, TME-driven immunosuppression, and potential on-target/off-tumor effects. To overcome these barriers, synergistic approaches that integrate innate immune therapies with checkpoint inhibitors, conventional treatments, innovative engineering, and precise modulation of the TME will be essential. These strategies hold the promise of translating scientific breakthroughs into durable, safe, and widely accessible treatments for patients with hematological malignancies.

Emicizumab is a FVIII mimetic antibody used in the treatment of inherited hemophilia A that could potentially be used in acquired hemophilia A (AHA) to achieve hemostasis and shorten hospital stay while reducing bypass therapies. We report on 12 cases of AHA patients treated with emicizumab in an academic center between January 2020 and June 2024. There were 5 male and 7 female patients, with median (interquartile range [IQR]) age and maximum inhibitor titer of 73 (60–76) years and 138 (36.75 -164.25) BU/mL, respectively. Ten patients were started on emicizumab while admitted inpatient, while 2 were started outpatient. The initial emicizumab dose was 3 mg/kg for 8 patients and 1.5 mg/kg for 4 patients; all patients then continued therapy with emicizumab 1.5 mg/kg every other week starting on day 8 and received immunosuppression with steroids and rituximab. Patients who began emicizumab therapy inpatient required a median (IQR) of 8 (6–10) days of bypass therapy and stopped bypass therapy 2.5 (1-5.25) days after emicizumab initiation. Furthermore, these patients were hospitalized for a median (IQR) of 10 (6.5-18.75) days and discharged 3 (2–6) days after starting emicizumab. One patient developed deep vein thrombosis and acute pulmonary thromboembolism while on emicizumab and was subsequently treated with anticoagulation. In conclusion, emicizumab appears to be an effective treatment in attaining hemostasis and reducing need of bypass therapy in patients with AHA. Emicizumab use in AHA may warrant monitoring for thromboembolic complications, and further study is needed to determine whether immunosuppression can be avoided.

While platelets are well-documented contributors to tumorigenesis, their role in multiple myeloma (MM) progression and risk stratification remains underexplored. To assess platelet function in MM and verify the prognostic value of platelet-related genes(PRGs) in patients with multiple myeloma, further providing new ideas for the development of MM. We combined the clinical assessment of platelet activation in MM patients with functional co-culture experiments using MM cell lines (RPMI8226, MM.1 S) to investigate platelet-driven tumor progression. Additionally, an integrated analysis of bulk (GSE124310) and single-cell transcriptomic datasets (GSE6477, TCGA-MM data, GSE4581, GSE24080,and GSE136337) was performed to identify platelet-related prognostic genes (PRGs). Through single-cell RNA sequencing, we identified aberrant erythroid-megakaryocyte components in multiple myeloma and further demonstrated dysfunctional platelet activity that promotes tumor cell proliferation and suppresses apoptosis. Using comprehensive bioinformatic screening across 116 algorithms, we identified a combined forward stepwise Cox and Ridge regression model as optimal and established a 13-gene platelet-related prognostic signature. The genetic risk model effectively stratified MM patients into distinct prognostic groups, with high-risk patients exhibiting poorer outcomes in both training and validation cohorts. Finally, we integrated the genetic risk model and clinically relevant information and visualized it with dynamic Nomogram plots, and the ROC and DCA curves demonstrated that the integrated model had better predictive ability. Our study establishes a significant association between platelet activity and disease progression in MM. The platelet-related prognostic signature we developed is correlated with patient outcomes and may have utility in risk stratification.

This study assesses haematological parameters as screening tools for identifying α zero (α⁰) thalassaemia candidates for DNA analysis. The Malaysia Thalassaemia Diagnosis Code (MTDC) uses mean corpuscular haemoglobin (MCH) < 25 pg to screen for suspected α⁰ thalassaemia carriers. Six haematological parameters from 304 cases genotyped by Gap-Polymerase Chain Reaction or Multiplex Ligation-dependent Probe Amplification were analyzed. Among the cases, 160 individuals (52.6%) were α⁺ thalassaemia silent carrier (-α/αα), comprising heterozygotes for -α^3.7, -α^4.2, –(α)^20.5 and -α^2.4. Twelve individuals (3.9%) were α⁺ thalassaemia carrier (-α/-α), including homozygous -α^3.7 and compound heterozygous -α^3.7 and -α^4.2. Meanwhile, 111 individuals (36.4%) were α⁰ thalassaemia carrier (--/αα) consisting of heterozygotes for --^SEA, --^GB, --^FIL, --^AW, and –^THAI deletions. Deletional Hb H disease (--/-α) was observed in individuals with compound genotypes such as -α^3.7/--^SEA, -α^3.7/--^GB, -α^3.7/--^AW, -α^4.2/--^SEA and -α^2.4/--^SEA. All parameters correlated with the number of α-globin gene deletions, with mean corpuscular volume (MCV) (r² = 0.73) and MCH (r² = 0.77) showing the strongest associations. Gender-specific MCH cut-offs of < 22.65 pg for males and < 22.25 pg for females demonstrated excellent diagnostic performance, with higher sensitivity and specificity in females (90.3% and 93.9%) than in males (89.5% and 88.9%). The findings indicate that the currently used MCH cut-off of 25 pg may be higher than optimal for identifying α⁰ thalassaemia carriers. A lower MCH threshold improves detection performance and may support refinement of the MTDC screening criteria to better prioritize high-risk individuals while reducing unnecessary DNA testing among α⁺ thalassaemia cases.

This study aimed to characterize the clinical characteristics, treatment patterns, survival outcomes, and prognostic factors of Chinese patients with primary mediastinal B-cell lymphoma (PMBCL). We retrospectively reviewed 69 consecutive patients with PMBCL treated at our center between 2010 and 2025. External validation was performed using data from the Surveillance, Epidemiology, and End Results (SEER) database (n = 1,460). The median age at diagnosis was 33 years (range, 18–62), with a female predominance (female-to-male ratio, 2.1:1). Most patients (92.8%, 64/69) received R-DA-EPOCH as frontline therapy, and 29.0% (20/69) additionally underwent consolidative radiotherapy (RT). Among 51 evaluable patients, the objective response rate was 90.2%, with a complete response rate of 74.5%. After a median follow-up of 74 months (range, 2–166), the estimated 5-year progression-free survival (PFS) and overall survival (OS) rates in whole cohort were 88.7% and 94.8%, respectively. Hematologic toxicity, predominantly febrile neutropenia, was the most common adverse event; nevertheless, 60.4% of patients maintained a relative dose intensity ≥ 100%. Consolidative RT did not confer a survival advantage, whereas age > 40 years emerged as an adverse prognostic factor for OS, a finding further validated in the SEER cohort. Chinese patients with PMBCL generally have favorable outcomes in the modern treatment era. However, older age (> 40 years) is associated with inferior survival. The R-DA-EPOCH regimen demonstrated high efficacy in this real-world setting, whereas additionally consolidative RT failed to provide a significant survival benefit.

Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) is a rare and clinically aggressive subtype of DLBCL, distinguished by its notably unfavorable prognosis. The clinical characteristics of this entity remain insufficiently characterized in the Chinese population. This study retrospectively analyzed 99 cases of EBV+DLBCL with available clinical data from Zhejiang Province, southeastern China. We comprehensively characterized the clinicopathological features of these patients and performed both univariate and multivariate survival analyses to identify independent prognostic factors. Specifically, 76.7% of patients presented with an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, 75.8% demonstrated extranodal disease involvement, and 47.5% exhibited B symptoms. Immunophenotypic analysis utilizing the Hans algorithm classified 82.8% (82/99) of cases as non-germinal center B-cell-like (non-GCB) cell-of-origin (COO). The overall survival (OS) rate was 45.4%, while the progression-free survival (PFS) rate was 30.3%. The majority of patients (71.7%, 71/99) received R-CHOP-type immunochemotherapy regimens. Both univariate and multivariate analyses identified R-CHOP-type therapy as a significant independent protective factor for both OS (P < 0.001) and PFS (P = 0.001). Multivariate analysis further revealed that hemoglobin (Hb) levels < 90 g/L, indicative of anemia, represented a potential strong adverse prognostic factor for OS, with moderate to severe anemia emerging as a clinically relevant predictor of poorer treatment outcomes. These findings underscore that EBV+DLBCL constitutes a clinically distinct lymphoma subtype associated with suboptimal outcomes under current chemoimmunotherapy. Notably, readily monitored Hb levels may serve as a practical prognostic biomarker for risk stratification in this patient population.

The success of immune checkpoint inhibitors (ICIs) has revolutionized oncology, with an increasing number of patients receiving treatment every year. However, this progress has been accompanied by a rise in immune-related adverse events (irAEs). One such irAE is thrombotic thrombocytopenic purpura (TTP), a rare and potentially life-threatening complication. This report presents a unique case of TTP following a single dose of pembrolizumab, a PD-1 inhibitor. A 76-year-old man with suspected advanced renal cell carcinoma received pembrolizumab as initial treatment. Eleven days later, the patient developed severe thrombocytopenia, bleeding problems, and hemolytic anemia. The following day, ADAMTS13 activity levels were measured at 3.8% (reference range: 40–130%), confirming the diagnosis of TTP. Given the patient’s poor overall condition and limited life expectancy, plasma exchange was not initiated. The patient passed away 15 days after receiving pembrolizumab. This case highlights that even a single dose of pembrolizumab can precipitate TTP, underscoring the need for clinician vigilance. A brief review of previously reported cases of PD-1 inhibitors associated with TTP is included.

Sickle cell disease (SCD) is a common and potentially life-threatening haematological disorder. In high-income countries, universal newborn screening and timely interventions have markedly reduced infant mortality. In contrast, in low-resource settings, diagnosis often occurs only in late childhood, once clinical manifestations have developed. The high cost, technical complexity, and limited availability of conventional diagnostic methods remain major barriers to implementing neonatal screening programmes in sub-Saharan Africa and other resource-constrained regions. We assessed the diagnostic performance of Sickle SCAN®, a prototype rapid immunoassay designed to qualitatively detect HbA, HbS, and HbC. The test is based on a lateral flow immunoassay format and provides results at the point of care. Cord blood samples from 365 newborns were analysed with Sickle SCAN® and results were compared against the reference standard of capillary electrophoresis. Sickle SCAN® accurately identified haemoglobin phenotypes in 97.3% of cases (95% CI: 95.0%–98.7%). For HbAA, sensitivity was 97.8% (95% CI: 94.9%–99.3%) and specificity was 96.5% (95% CI: 92.0%–98.9%). For HbAS, sensitivity was 95.8% (95% CI: 90.5%–98.6%) and specificity 98.0% (95% CI: 95.3%–99.3%). Importantly, no false-positive or false-negative results were observed for HbSS and HbAC, yielding 100% sensitivity and specificity for these phenotypes. Our findings demonstrate that Sickle SCAN® is a highly accurate, rapid, and low-cost tool for neonatal SCD screening. Its use could substantially reduce diagnostic delays, lower programme costs, and improve accessibility to early detection in resource-limited settings, thereby contributing to improved child survival.

Around 60–80% of patients with immune thrombocytopenia (ITP) experience disease relapse after stopping corticosteroids. Rituximab (RTX) is an effective second-line treatment. Low-dose RTX has shown similar efficacy to standard dose, but the optimal dosage remains uncertain. This multicentre, prospective, open-label, randomised controlled trial aimed to compare the long-term efficacy (5-year follow-up) and 1-year safety of two low-dose RTX regimens in Chinese adult patients with glucocorticoid-resistant/dependent or relapsed ITP. Patients (n = 104) were randomised 1:1 to group A (RTX 100 mg weekly for 4 weeks) or group B (RTX 375 mg/m² once). The primary outcome was overall response (OR) at 3 months after RTX initiation. Response was followed up until disease relapse or for 5 years. Forty-nine patients in Group A and 51 patients in Group B completed the intervention. At 3 months after RTX initiation, 32 patients in group A (65.3%) and 33 patients in group B (64.7%) achieved OR, and the complete response rate was 42.9% (21/49) in group A and 39.2% (20/51) in group B. The sustained response rates at 6 months, 1, 2, and 5 years were 59.2%, 42.9%, 28.6%, and 20.4% in group A and 58.8%, 43.1%, 33.3%, and 17.6% in group B. These variables were not statistically different between two groups. The most common adverse events were upper respiratory tract and pulmonary infections. RTX 375mg/m² once showed similar long-term efficacy compared to RTX 100 mg weekly for 4 weeks, with a comparable 1-year safety profile; both being well tolerated. The single-dose regimen may be preferable due to greater patient convenience and reduced economic burden.

Trial registration

ClinicalTrials.gov Identifier- NCT01719692 (Registration date: October 26, 2012).