Annals of Hematology最新文献

Decitabine shows favorable efficacy in induction and maintenance therapy for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but its role in pre-transplant conditioning still has not been established. We performed a systematic review and meta-analysis of comparative studies investigating the effects of adding decitabine to conditioning regimens in AML/MDS patients undergoing allogeneic hematopoietic stem cell transplantation. Meta-analysis was conducted with Review Manager 5.4. For time-to-event outcomes, pooled hazard ratios (HRs) were calculated using generic inverse-variance method. For dichotomous data, pooled risk ratios (RRs) were calculated using Mantel-Haenszel method. Fixed-effects model was adopted if there is no significant heterogeneity. Literature search and study selection identify 9 eligible studies, including 2 randomized controlled trials and 7 retrospective comparative studies. Meta-analysis show that addition of decitabine to conditioning regimen is associated with significantly better overall survival (HR 0.61; 95% CI: 0.49–0.76; P < 0.00001), reduced risk of relapse (HR 0.58; 95% CI: 0.46–0.73; P < 0.00001), and better disease-free survival (HR 0.67; 95% CI: 0.55–0.81; P < 0.0001) without increasing non-relapse mortality (HR 0.82; 95% CI: 0.56–1.18; P = 0.28) and grade II-IV acute graft-versus-host disease (RR 0.75; 95% CI: 0.54–1.04; P = 0.08).

Research on the optimal consolidation therapy for adult T-cell acute lymphoblastic leukemia (T-ALL) remains limited, and how to integrate pediatric-inspired chemotherapy with allogeneic hematopoietic stem cell transplantation (SCT) is less addressed. Based on retrospective analysis indicating that 4 doses of pegylated-asparaginase (PEG-Asp) prior to SCT were optimal for survival, we designed a PEG-Asp-intensified pediatric-inspired regimen, PDT-ALL-2016, for adult T-ALL (NCT03564704). In this protocol, SCT administered following 4 or 5 doses of PEG-Asp. The impact of PEG-Asp on transplantation outcomes was evaluated in two cohorts: the prospective PDT-ALL-2016 cohort (2016.1-2021.12, N = 63) and the retrospective adult regimen cohort (2008.1-2015.12, N = 61). With intensified PEG-Asp consolidation, the prospective cohort exhibited superior survival compared to the retrospective cohort. Furthermore, within the prospective cohort, patients who received non-truncated PEG-Asp demonstrated better survival than those who received a truncated dose. Then, the entire cohort was stratified into high-dose (4–5 doses, N = 45), medium-dose (2–3 doses; N = 33) and low-dose (0–1 doses; N = 46) groups, based on the number of PEG-Asp doses administrated pre-SCT. The high-dose group showed superior survival compared to the other two groups in both the entire cohort and in subgroup analysis. Our findings indicate that high-dose PEG-Asp is associated with improved outcome in adult T-ALL undergoing SCT.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, abnormal hematopoiesis, and extramedullary hematopoiesis. Abnormalities of the tumor microenvironment and immune system may be involved in the MF physiopathology and progression, particularly affecting innate myeloid cells (IMCs) such as myeloid dendritic cells (mDCs), plasmacytoid dendritic cells (pDCs) and monocytes. This study aims to quantitatively assess these cell populations in MF patients and their association with clinical outcomes. A cohort of 21 MF patients from the Universidade Federal de São Paulo was analyzed. Peripheral blood samples were evaluated using flow cytometry to quantify pDCs and monocytic subpopulations, including classical, intermediate, and non-classical monocytes. Comparative analyses were conducted with 12 healthy controls. MF patients exhibited a significant reduction in both the relative and absolute numbers of circulating mDCs and pDCs compared to healthy controls. The pDC reduction was more pronounced in patients with grade 3 fibrosis, anemia and splenomegaly. While total monocyte percentages were slightly lower in MF patient, the distribution of monocytic subpopulations showed no significant differences between groups. Patients with JAK2 mutations demonstrated higher concentrations of intermediate monocytes. The findings reveal a remarkable depletion of pDCs in MF patients, particularly those with advanced clinical manifestations such as anemia and splenomegaly. This study highlights the potential role of dendritic cells as biomarkers for disease severity and progression in MF. Further research is needed to elucidate the functional implications of these cells and their interactions within the MF microenvironment, potentially guiding new diagnostic and therapeutic strategies.

Despite advances in treatment, long -term survival in patients with acute myeloid leukemia (AML) remains unsatisfactory. Standard induction chemotherapy achieves complete remission (CR) rates of 60%-80% in newly diagnosed AML patients; however, relapse and chemoresistance persist as major challenges. Combined multi-target therapeutic regimens have the potential to enhance response rates and improve survival outcomes. In this propensity score matching (PSM), single-center retrospective study, we evaluated the efficacy and safety of a novel regimen-venetoclax-azacitidine combined with low-dose idarubicin and cytarabine (VAIA)།versus standard idarubicin-cytarabine (IA) therapy in newly diagnosed AML patients. Twenty-six patients treated with VAIA were compared with 52 patients treated with IA, with well-matched clinical and molecular baseline characteristics. The VAIA cohort demonstrated significantly higher CR and measurable residual disease (MRD)-negative CR rates compared to the IA cohort (84.3% vs. 61.5%, P = 0.037; and 80.8% vs. 53.8%, P = 0.026, respectively). Moreover, VAIA was associated with improved overall survival (1-year OS: 76.9% vs. 57.7%, P = 0.031) and leukemia-free survival (1-year LFS: 65.4% vs. 46.2%, P = 0.042). Subgroup analysis revealed that adverse-risk patients particularly benefited from VAIA (1-year OS: 69.2% vs. 32%, P = 0.045; 1-year LFS: 61.5% vs. 20%, P = 0.046). In both treatment groups, MRD-negative patients exhibited significantly longer survival than MRD-positive patients. The VAIA regimen also showed superior therapeutic effects in patients particularly in patients with adverse or complex cytogenetics and adverse risk, with an acceptable and manageable toxicity profile. These findings support further prospective evaluation of the VAIA regimen in AML.

Olverembatinib is a novel third-generation TKI available in mainland China. However, there are only a few published clinical reports. In this study, we aimed to investigate the efficacy and safety of an olverembatinib-venetoclax regimen before bridging to HSCT in adult Ph/BCR-ABL1 + ALL patients with refractory/relapsed disease (n = 2) or persistent minimal residual disease (MRD) (n = 15). Seventeen Ph + ALL patients who were admitted to our center between February 2022 and January 2023 were enrolled. Four patients harbored a T315I mutation. In all, 100% achieved hematologic complete remission, and 70.6% achieved complete molecular remission. With a median follow-up of 856-day post-HSCT, the 2-year overall survival and relapsed free survival rates was 88.2 ± 7.8% and 79.4 ± 10.9%, respectively. The findings of this study suggest that in Ph + ALL patients with disease recurrence and persistent MRD positivity, olverembatinib-venetoclax regimen showed a high molecular response rate and was well-tolerated in MRD clearance bridged to allo-HSCT.

Alpha-thalassemia is primarily caused by large deletions in the HBA1 and HBA2 genes, but a minority of cases result from non-deletional mutations, including variants in untranslated regions (UTRs) that affect mRNA regulation. The 3′UTR is crucial for post-transcriptional control, influencing mRNA stability, localization, and translation via binding elements for RNA-binding proteins and microRNAs. We describe two patients with persistent microcytosis and normal iron levels. Standard hematological analyses were complemented by high-performance liquid chromatography (HPLC) and capillary electrophoresis to rule out common hemoglobinopathies. Molecular analysis was performed using multiplex PCR and direct sequencing of the HBA1 3′UTR. Patient 1, a 3-year-old Nigerian boy, carried a novel insertion mutation (HBA1:c.*119_120insT) five nucleotides downstream of the transcription termination signal. Patient 2, a 31-year-old Moroccan woman, exhibited a missense variant (HBA1:c.*150C > A) located 40 nucleotides downstream of the TTS. Both variants are located within regulatory regions of the HBA1 3′UTR. In silico analyses suggest disruption of RNA secondary structure, impaired interactions with HuR and AUF1 proteins, altered microRNA binding (e.g., miR-16-5p), and potential interference with polyadenylation signals, resulting in mRNA instability and reduced alpha-globin synthesis. These two novel mutations in the 3′UTR of HBA1 expand the spectrum of non-deletional alpha-thalassemia variants and highlight the importance of regulatory regions in globin gene expression. Their inclusion in routine molecular screening may enhance diagnostic accuracy in cases of unresolved microcytic anemia.

Treatment advances for classical Hodgkin Lymphoma (cHL) have improved outcomes, but studies are lacking in older patients. This analysis aims to investigate survival trends in older individuals with cHL using the Texas Cancer Registry (TCR). Adults ≥ 65 years with cHL were separated into three eras: 1995–2002, 2003–2010, and 2011–2017. Pearson chi-squared test and cox-proportional hazard models along with hazard ratios (HR) and 95% confidence intervals (95% CI) compared demographic factors, and survival trends were assessed by Kaplan-Meier methodology. There were 386 (37.4%), 336 (32.5%), and 311 (30.1%) individuals diagnosed in 1995–2002, 2003–2010, and 2011–2017, respectively. Median DSS per era was 97 months (95% CI 50.7, 143.3), 158 months (95% CI 132.5, 183.5), and not reached, (p=0.383), and median OS was 32 months (95% CI 23.4, 40.6), 37 months (95% CI 23.5, 50.5), and 40 months (95% CI 26.8, 53.1), respectively (p=0.693). Median OS was worse for blacks and Hispanics vs non-Hispanic whites (p=0.007), increasing age (p<0.001), and higher poverty index (p=0.006). While DSS and OS have not improved over the past two decades for older individuals, there are disparity dependent survival differences by race, age, and poverty index. Strategies to reduce these disparities are needed.

This study investigates the pharmacokinetic variability and exposure-response relationships of Venetoclax (VEN) in adult patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. The study was conducted in a real-world clinical setting and included 48 patients who were treated with VEN in combination with azacytidine. We found significant inter-individual variability of 68% and intra-individual variability of 39% in plasma VEN concentrations. In addition, higher VEN concentrations were associated with better hematological responses. Median overall survival for the entire cohort was 17.8 months, with 1- and 2-year survival rates of 51% and 36.4%, respectively. A comparison of the 14-day VEN and 28-day VEN protocols showed that patients benefited from longer treatment durations, which resulted in more courses being administered. Plasma concentrations in the 14-day VEN protocol were higher than in the 28-day VEN protocol (2330 + 1675 ng/mL vs. 1503 + 966 ng/mL, respectively) without an increase in toxicities. The optimal protocol would be 400 mg/14d if we consider survival as a function of the 1818ng/mL cutoff. These results highlight the importance of considering therapeutic drug monitoring (TDM) as a strategy to optimize treatment outcomes by balancing efficacy and safety.

Quantification of foetal haemoglobin (HbF) via high-performance liquid chromatography (HPLC) remains a critical parameter for monitoring therapeutic response to hydroxyurea (HU) in patients with sickle cell disease (SCD). However, its routine application is constrained in low-income settings such as Nigeria due to limited accessibility. The platelet-to-neutrophil ratio (PNR), an emerging inflammatory biomarker, has demonstrated prognostic relevance in several disease conditions. This study investigates the potential utility of PNR as a surrogate monitoring tool in SCD patients receiving HU therapy. This was a retrospective analysis of data derived from the Children’s National Hospital Natural History Study of Sickle Cell Disease, conducted in Washington, D.C., USA. Medical records of patients with SCD were reviewed from 1 September 2013 to 14 September 2023. Associations between PNR, HU use, HbF concentration, and reticulocyte count were evaluated. T-tests was used for continuous variables and chi-square tests for categorical variables. Regression analysis was used to evaluate the predictors of hydroxyurea use. A p-value of < 0.05 was considered statistically significant. Of 437 patient records reviewed, 222 (50.8%) were male, and 312 (71.4%) were receiving HU. The majority (81%) had no history of transfusion. Patients on HU exhibited significantly higher platelet counts, HbF levels, and PNR values (p = 0.0008, p < 0.0001, and p < 0.0001, respectively). In multivariate logistic regression, both HbF (OR: 1.121; 95% CI: 1.051–1.196; p < 0.001) and PNR (OR: 1.014; 95% CI: 1.005–1.024; p = 0.0022) were independently associated with HU use. No significant associations were observed between HU use and age group, haemoglobin phenotype, transfusion history, or BMI (p > 0.05). The PNR demonstrates a significant association with HU use and HbF levels, indicating its potential as a low-cost, accessible biomarker for monitoring HU therapy in SCD. Although this analysis was based on data from a high-resource setting, the findings underscore the relevance of PNR as a feasible monitoring alternative in resource-constrained environments. Further validation in low-income contexts is warranted to establish population-specific reference intervals and inform clinical practice.

Introduction

Haematology plays a crucial role in the management of pregnant females as blood disorders are common in these patients which can significantly impact on maternal and fetal health. This paper explores how haematology can adapt its practice to address the unique challenges posed by physiological/pathological changes during pregnancy.

Methods

A comprehensive review of the physiological changes in blood volume, coagulation, and haematological parameters during pregnancy was conducted. Case series of pregnant women with various blood disorders, including gestational thrombocytopenia, iron deficiency anaemia, venous thromboembolism, sickle cell disease, and thalassemia, were analysed to illustrate management strategies.

Results

The physiological increase in blood volume during pregnancy leads to dilutional effects on haematological parameters, complicating diagnosis and management. Conditions such as gestational thrombocytopenia and anaemia require tailored approaches, while the increased risk of thromboembolic events necessitates proactive risk assessment and prophylactic measures. The management of pre-existing blood disorders demands a multidisciplinary approach, emphasizing collaboration between haematologists and obstetricians.

Discussion

Effective management of blood disorders in pregnancy is essential on understanding physiological changes, individualized care plans, and patient education. Empowering patients with knowledge about their conditions and potential complications is essential for optimizing outcomes.

Conclusion

Adapting haematology practice for pregnancy management is vital for addressing the complexities of blood disorders during the critical pregnancy period. A multidisciplinary approach, ongoing education, and research advancements are essential for improving maternal and fetal health outcomes. By fostering collaboration across specialties, healthcare providers can work towards achieving the best possible outcomes for pregnant woman with haematological conditions.