Annals of Hematology最新文献

Sickle cell disease (SCD) is a hereditary hemoglobinopathy that imposes a significant burden on global health. Individuals with SCD often experience multiple nutritional deficiencies, among which vitamin D deficiency has emerged as a critical yet under recognized factor contributing to disease complications. This study aimed to assess the vitamin D status in patients with SCD compared to a matched healthy control group, and to explore its correlation with clinical and biological parameters, including the frequency of vaso-occlusive crises (VOC). A cross-sectional study was conducted between January and June 2024 at Bechir Hamza Children’s Hospital, Tunis. Sixty-four SCD patients and 63 healthy controls were enrolled. Vitamin D [25(OH)D] levels, along with hematologic and biochemical markers, were measured. Statistical analyses included t-tests, chi-square test, ANOVA, and Spearman correlation. Vitamin D levels were significantly lower in the SCD group (15.05 ± 6.6 ng/mL) compared to controls (22.51 ± 12.54 ng/mL, p = 0.026). Among SCD patients, 78.2% (50) had Vitamin D deficiency (< 20ng/mL), 20.3% (13) had Vitamin D insuffisancy (20–30 ng/mL) and only one patient (1.5%) had normal vitamin D status (> 30 ng/mL). Vitamin D levels were inversely correlated with age, total bilirubin, parathyroid hormone (PTH), and frequency of VOC, and positively correlated with hemoglobin concentration and socioeconomic status. SCD patients with vitamin D deficiency experienced significantly more VOC episodes per year. Vitamin D deficiency is highly prevalent among SCD patients and is associated with increased disease severity. Routine screening and appropriate supplementation should be considered as part of comprehensive SCD management strategies.

Hypomethylating agents (HMA) alone or in combination with venetoclax (VEN) are a mainstay for disease control in elderly acute myeloid leukemia (AML). We evaluated the non-inferiority of HMA monotherapy compared to HMA/VEN combination in 227 AML patients aged ≥ 75 years receiving HMA or HMA/VEN combination. No difference in overall survival (OS) was observed between the two groups, with HMA monotherapy demonstrating statistical non-inferiority. HMA-treated patients with favorable performance status had longer OS. The HMA/VEN group experienced higher mortality and worse QoL. HMA monotherapy offers comparable survival outcomes to HMA/VEN with reduced toxicity in elderly AML patients.

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.