Annals of Hematology最新文献

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).

Vanishing bile duct syndrome (VBDS) is a rare, and often fatal complication of Hodgkin lymphoma (HL), characterized by progressive intrahepatic bile duct loss and severe cholestasis. Management remains ill-defined, particularly in patients with refractory HL and significant hepatic dysfunction. We present a case of a young woman with biopsy-proven VBDS who experienced disease progression and worsening cholestasis despite second-line chemotherapy, corticosteroids, and brentuximab vedotin. Salvage therapy with pembrolizumab was initiated, resulting in a complete metabolic remission of HL and normalization of liver function. Notably, the patient did not experience immune-related hepatic adverse events. To our knowledge, this is the first report of HL-related VBDS successfully treated with programmed death-1 blockade. This case suggests that immune checkpoint inhibitors may be a viable therapeutic option for patients with HL-related VBDS, even in the setting of severe hepatic dysfunction.

We report the case of a man in his 50’s diagnosed with Bernard-Soulier syndrome (BSS) in childhood who developed refractory gluteal bleeding following a fall accident. The patient underwent four hematoma evacuation procedures and multiple platelet transfusions, including HLA (human leukocyte antigen) -matched platelet concentrates, without achieving sustained hemostatic control. Given the lack of response to platelet transfusion and ongoing bleeding risk, Eptacog Alfa (recombinant activated factor VII; rFVIIa) was administered for 4 days, following the dosing regimen recommended for Glanzmann thrombasthenia in surgical bleeding settings. Hemostasis was achieved shortly after rFVIIa administration, and no further surgical evacuation was necessary. Importantly, no thromboembolic complications occurred despite the use of rFVIIa. This case demonstrates that rFVIIa can serve as an effective adjunctive hemostatic therapy in patients with BSS who are refractory to platelet transfusions. We reviewed the existing literature on rFVIIa use in patients with BSS and summarized the clinical contexts, dosing strategies, efficacy, and safety outcomes. Our experience suggests that early consideration of rFVIIa may help prevent repeated surgical interventions and reduce bleeding-related morbidity in complex cases.

Venetoclax (VEN) combined with hypomethylating agents (HMA) is a standard treatment for unfit acute myeloid leukemia (AML) patients, but the conventional 28-day cycle often leads to prolonged cytopenias and infection risks. Recent studies suggest shorter VEN regimens may improve safety without compromising efficacy, but this remains controversial. To this end, we performed a systematic review and meta-analysis to compare the impact of VEN duration in patients receiving VEN-HMA. A comprehensive literature search was conducted in PubMed and Embase up to May 28, 2025. The Cochran Q test and I-squared statistics were used to identify the heterogeneity among the included studies. The network meta-analysis was performed by employing The mtc.model and mtc.run functions of the gemtc R package. We performed all statistical analyses using R 4.0.3. Six studies with 728 patients were included. Meta-analysis showed no significant difference in remission rates between shorter (≤ 14 days) and longer (> 14 days) treatments (RR = 1.07, 95% CI: 0.95–1.20). Network meta-analysis of 14-day (VEN14), 21-day (VEN21), and 28-day (VEN28) regimens found no statistically significant differences in remission rates or overall survival (OS), with VEN14 ranking first for both remission efficacy and survival benefit. Although grade 3/4 granulocytopenia was similar across groups, VEN21 correlated with significantly lower febrile neutropenia versus VEN28 (RR = 0.56, 95% CI: 0.29–0.98). Shorter VEN courses (14–21 days) appear to maintain comparable efficacy to the standard 28-day course, with VEN21 potentially offering a better safety profile regarding febrile neutropenia, supporting the individualization of treatment duration to improve tolerability in unfit AML patients.

This study examined the clinical, genetic, and treatment response characteristics of pediatric patients with acute myeloid leukemia (AML) treated according to the 2004 and 2012 AML-BFM protocols. This study aimed to determine survival outcomes and the factors affecting them, and to compare the results with international data. This study retrospectively evaluated pediatric AML patients aged < 18 years in eastern Turkey between January 2010 and December 2023. The AML-BFM 2004 and AML-BFM 2012 protocols were applied to the patients. The risk groups of the patients were determined based on their responses to chemotherapy and genetic results. Survival analyses were conducted using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were used. Forty-nine patients were included in this study. The median age at diagnosis was 12 years, and 51% of the patients were female. The most common morphological subtype was AML M3, accounting for 32.7% of cases. Complete remission was achieved in 81.6% of patients after induction therapy, whereas 12.2% died during this phase. Relapse occurred in 26.5% of patients. Overall, 38.8% of patients died. AML-M3 patients had a median overall survival (OS) of 113 months, which was better than that of non-AML-M3 patients. Five-year survival rates were 94% for AML-M3 patients and 43% for non-AML-M3 patients. Lower survival rates were observed in patients with leukocyte counts ≥ 50 × 10⁹/L, low hemoglobin levels, non-AML-M3, and poor induction response. Mortality was higher in patients younger than two years and > 14 years. There were no significant differences in mortality, survival, or relapse rates between the AML-BFM 2004 and AML-BFM 2012 protocols (p > 0.005). No significant association was observed between mortality and leukapheresis. Further research should focus on developing personalized treatments for high-risk patients and those without non-AML-M3, given their poorer survival rates than those of AML-M3 patients.

High-dose chemotherapy with autologous stem cell transplantation (ASCT) is a key consolidative therapy for primary central nervous system lymphoma (PCNSL). However, the optimal regimen for mobilizing haematopoietic stem cells remains undefined in this population, leading to unpredictable failure rates and suboptimal cell yields. We retrospectively analysed data from 142 patients with histologically confirmed PCNSL who underwent stem-cell mobilisation before ASCT. Three mobilisation strategies were compared: high-dose cytarabine (HD-Ara-C)–based mobilisation (n = 64), plerixafor plus G-CSF (n = 60), and cyclophosphamide (CTX, n = 18). Mobilisation success, CD34⁺ cell yield, toxicity, and predictors of collection outcomes were evaluated. Patients in the HD-Ara-C–based mobilisation group achieved a 100% success rate, significantly outperforming CTX (77.8%) and steady-state mobilisation (98.3%) while delivering a markedly superior median CD34⁺ cell yield (20 × 10⁶/kg vs. 12.7 and 10 × 10⁶/kg, p < 0.001). Notably, 79.7% of patients in the HD-Ara-C–based mobilisation group were classified as “very good” mobilisers,with all “poor” mobilisers confined to the other groups. Crucially, we identified and validated the first-day peripheral blood CD34⁺ cell count as a powerful predictor of collection outcome. A threshold of > 31 cells/µL predicted successful collection (> 2 × 10⁶/kg) with an AUC value of 0.94 (98.6% specificity, 78.6% sensitivity). Higher thresholds predicted optimal and high-yield collections. Although grade 4 thrombocytopenia was more common with HD-Ara-C, it was manageable with supportive care. HD-Ara-C–based mobilisation is a highly effective strategy for PCNSL, ensuring universal success and maximizing CD34⁺ cell yields. The first-day CD34⁺ cell count provides a robust, real-time tool for guiding apheresis. HD-Ara-C–based mobilisation should be considered the preferred regimen for fit patients, with steady-state mobilisation as an alternative for selected cases.

Ph-like ALL, a high-risk subgroup of B-cell ALL, is associated with a poor prognosis. The genetic diversity observed across different ethnicities underscores the importance of population-specific studies to gain a deeper understanding of its genetic drivers and clinical outcomes. This study aims to characterize the Ph-like ALL group in Turkish pediatric B-ALL patients and evaluate our custom-developed gene panel for subgroup identification. To identify the Ph-like subgroup, RNA was isolated from 35 bone marrow samples, and targeted mRNA expression analysis was performed by RT-qPCR using a custom-designed panel consisting of 96 genes. Additionally, the Archer FusionPlex ALL Panel (ArcherDX, Boulder, CO) was employed for further evaluation of patients demonstrating the highest similarity rates. This study employed a gene panel designed to differentiate Turkish Ph-like ALL patients within the Ph-negative group, identifying two Ph-like cases (6%). The panel demonstrated 96.9% sensitivity and 93.9% specificity in detecting Ph-like ALL, highlighting its effectiveness in differential diagnosis. In the Ph-like cases, alterations in PAX5 (rs143723948, rs879020782) and IKZF1 (rs6975767) were observed. Both cases shared a novel EPOR variant (rs1312770718), with no known clinical impact. Additionally, a novel variantin the PTPN11 gene was interpreted as “Possibly Damaging”. This study introduces a gene profiling-based diagnostic approach for the Ph-like subgroup of pediatric B-ALL in Turkish patients. The integration of targeted tyrosine kinase inhibitors into treatment protocols, guided by the diagnostic algorithm, aims to improve prognosis and survival, advancing personalized management of Ph-like ALL.

Tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML), yet persistent leukemia stem cells (LSCs) remain a barrier to cure. PPARγ agonists like pioglitazone have been proposed to enhance eradication of LSCs when used alongside TKIs. This study investigated the impact of adding pioglitazone to imatinib therapy in 26 newly diagnosed chronic-phase CML patients. Patients received imatinib (400 mg) plus pioglitazone (15 mg) daily for six months, with follow-up extending to 60 months. Treatment responses and adverse events were recorded, and expression levels of CITED2 and HIF2α genes were measured before and after therapy, compared to a control group of 52 matched patients treated with imatinib alone. The combination therapy showed improved early cytogenetic and molecular responses, though long-term outcomes were not significantly different. Significant reductions in median CITED2 (from 276.3 to 2.6; P = 0.005) and HIF2α (from 2.7 to 1; P = 0.026) expression were observed post-treatment. These results suggest that pioglitazone may enhance early molecular response and suppress LSC-associated genes, but further research is needed to confirm its long-term benefit and clarify the role of PPARγ modulation in CML management. Clinical Trial Number: NCT04883125.

Donor cell-derived myelodysplastic syndrome/acute myeloid leukemia is a rare but serious complication of allogeneic hematopoietic stem cell transplantation, and its optimal treatment has not been established. Here, we report a case of a 44-year-old woman who was diagnosed with donor cell-derived myelodysplastic syndromes with excess blasts carrying RAD21 and KMT2D mutations after six-year clinical remission of her initial acute myeloid leukemia treated with bone marrow transplantation from an unrelated male donor. The disease subsequently transformed to acute myeloid leukemia harboring a newly acquired FLT3 internal tandem duplication mutation. Azacitidine and venetoclax with cytarabine were both ineffective, but gilteritinib monotherapy rapidly reduced blasts and achieved near complete remission. The patient then underwent haploidentical stem cell transplantation from her son, followed by gilteritinib maintenance therapy. She achieved complete remission with clearance of donor cell-derived mutations and has remained in remission for more than one year. To our knowledge, this is the first case report of a relapsed FLT3-mutated donor cell-derived acute myeloid leukemia who was successfully treated with a FLT3 inhibitor, gilteritinib, which highlights the potential effectiveness of gilteritinib not only as a salvage therapy but also as an effective bridging and maintenance therapy in relapsed FLT3-mutated donor cell-derived acute myeloid leukemia.