Acta Haematologica最新文献

Introduction: Changes in the number and functional capacity of T-lymphocytes have been reported in chronic lymphocytic leukemia (CLL) patients. The aim of this study was to examine the prognostic significance of T-lymphocyte subgroups in CLL patients.

Methods: Eighty-three previously untreated patients were retrospectively enrolled and flow cytometry results at diagnosis were examined. No difference was found in T-lymphocyte parameters according to age, gender, and disease stage.

Results: The CD4 and CD7 percentages, CD4/MBC (Malignant B Cell), CD8/MBC, and CD7/MBC values at diagnosis were significantly lower in patients with a progressive disease. T-lymphocyte percentages were significantly lower in deceased patients. In the univariate regression model, T-lymphocyte percentages, T-lymphocyte/MBC ratios, HLA-DR+ percentage, Rai stage (intermediate + high risk), Binet stage (B+C), and beta-2 microglobulin level had significant effects on both progression-free survival (PFS) and overall survival (OS); treatment status (yes) had a significant effect only on PFS, while age at diagnosis (≥ 65 years) had a significant effect only on OS. In the multivariate regression model, Rai stage, CD7/MBC ratio, and treatment status (yes) had a significant effect on PFS; Rai stage and CD8/MBC ratio had a significant effect on OS.

Conclusion: Lower T-lymphocyte/MBC ratios at diagnosis could be a marker for higher risk of CLL progression.

Introduction: Heavy menstrual bleeding (HMB) poses a significant concern among adolescents and can arise from bleeding disorders. This study aimed to compare the clinical presentations and treatment of adolescents with HMB, distinguishing those with and without an underlying bleeding disorder.

Methods: We conducted a retrospective analysis of adolescent patients presenting with HMB during 2014-2022 at specialized hematology-adolescent clinics in two tertiary referral hospitals in Israel. The study was approved by the Institutional Review Boards.

Results: 77 adolescents underwent evaluation for HMB, and 19 of them were diagnosed with various bleeding disorders: platelet aggregation defects (5), immune thrombocytopenia (1), Glanzmann thrombasthenia (1), VWD type 1 (5), type 2A (1), type 3 (3), and coagulation factor deficiencies (3). Notably, 38 patients (49%) were hospitalized. A higher bleeding score (BAT) significantly correlated with hospitalization and a lower hemoglobin level (p<0.001). We did not find any significant differences between adolescents with or without a bleeding disorder regarding age of presentation, time from menarche, BAT, hemoglobin or platelet count.

Conclusion: Our findings revealed the clinical presentations and treatments of adolescents with HMB are similar, regardless of the presence of a bleeding disorder. This emphasizes the importance of thorough evaluation in all adolescents presenting with HMB.

Introduction: Ropeginterferon alfa-2b-njft (ropeg) was approved and recommended as a preferred cytoreductive treatment for polycythemia vera (PV). The approved regimen requires an initial dose of 100 μg or 50 μg if transitioning from hydroxyurea (HU) and up-titrations of 50 μg every two weeks to 500 μg maximumly. The time to achieve the plateau dose takes approximately 20 weeks. This study compares the approved regimen with a higher initial dose and accelerated dose titration (HIDAT) regimen. Methods and Conclusion: ECLIPSE-PV is a randomized, open-label, multicenter trial in patients with PV in the US and Canada. Patients received ropeg either per the approved dosing schema, or HIDAT regimen, i.e., 250 μg on Day 0, 350 μg at Week 2, and 500 μg from Week 4 thereafter if tolerable. The primary endpoint is complete hematologic response (CHR) rate at Week 24. CHR is defined as hematocrit <45%, white blood cells <10×109/L, platelets ≤400×109/L without phlebotomy in the previous 12 weeks. Secondary endpoints include molecular response, safety and tolerability, and quality of life. A total of 111 patients were randomized and the last patient was enrolled on June 21, 2024. As of November 12, 2024, the discontinuation rate was 14.4% and 16 patients (14.4%) completed the study. The study is expected to be completed in the summer of 2025. This is the first prospective trial comparing two dosing regimens of ropeg. The results will inform the optimal treatment strategy for patients with PV.

INTRODUCTION Distress negatively affects cancer outcomes. The National Comprehensive Cancer Network (NCCN) recommends screening patients for distress by a self-reported scale (0-10) and to refer those with scores ≥ 4 to supportive services (SS). Little is known about the prevalence of distress and healthcare utilization in classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs): polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF). METHODS We retrospectively identified MPN patients at our center to measure the proportions of patients with distress ≥ 4 evaluated by a SS [chaplaincy, integrative oncology, palliative medicine, psychiatry, psychology, and social work (SW)] or had acute care utilization (ACU; ≥ 1 ED visit or hospitalization) within six months of electronic distress screening (EDS). We also obtained sociodemographic, disease characteristics, and symptom score data to stratify variables associated with distress. RESULTS Among 141 patients (44 PV, 49 ET, 48 MF), the median age was 63 years (range, 25-89). Most patients identified as female (62%), White (77%), and completed EDS within three months of diagnosis (55%). Of 75/141 (53%) who reported distress ≥ 4, only 25/75 (33%) were evaluated by SS, and 23/75 (31%) had ACU within six months of EDS. Patients with distress ≥ 4 evaluated by SS had significantly higher ACU (48% vs. 14%; p=0.009). Distress was associated with higher symptom scores and more ED visits but not gender, race, ethnicity, diagnosis, relationship status, or insurance. CONCLUSION Despite consensus recommendations, most patients with distress ≥ 4 were not evaluated by SS. Future work should identify ways to better use patient-reported outcomes to promote early intervention.

Introduction: Ferroptosis offers novel perspectives for treating multiple blood-related diseases, yet its role in aplastic anaemia (AA) is rare. This study aimed to explore key ferroptosis-related genes (FRGs) in AA using bulk and single-cell RNA sequencing (scRNA-seq) data.

Methods: scRNA-seq and bulk RNA-seq data, along with FRG lists, were obtained from public databases. Differentially expressed FRGs (DEFRGs) between AA and control samples were identified, followed by functional enrichment and protein-protein interaction analyses. Single-cell analyses were conducted to reveal main cell types in samples and DEFRGs activity in each cell was assessed. Moreover, DEGs between AA and control samples at the cellular level were explored, followed by integration with DEFRGs to determine common key genes. KEGG pathway analysis of these genes was performed at the cellular level. Immune infiltration analysis was used to evaluate the relationship between key genes and immune cells.

Results: A total of 38 DEFRGs were identified, enriched in pathways such as the intrinsic apoptotic signalling pathway. scRNA-seq analysis identified seven cell types, with elevated DEFRGs activity in platelets and stromal cells. Key genes DDIT4 and NCF2, identified through integrated analysis, were involved in autophagy, mTOR signalling, and osteoclast differentiation pathways. Moreover, their expressions were positively correlated with activated dendritic cells in AA samples.

Conclusion: Our findings highlight the roles of DDIT4 and NCF2, in AA progression, providing potential insights for further mechanistic exploration of AA.

Introduction: Many reports indicate that the occurrence of multiple myeloma (MM) is closely related to inflammation and immunity. Although the survival rates have been gradually improving in recent years, the cure rate is still not optimistic enough. Therefore, it is necessary to continue exploring the causes of MM.

Methods: This study utilizes Mendelian randomization (MR) analysis to establish the connection between inflammatory factors, immune cells, and the occurrence of MM.

Results: In MR studies, a significant correlation was observed between interleukin-1 receptor antagonist (IL-1Ra), tumor necrosis factor receptor 1 (TNFR1), memory B-cell percentage of B cells (memory B-cell %B cells), and immunoglobulin D-positive, CD24-negative percentage B cells (IgD+ CD24- %B cells) with the onset of MM. In particular, IgD+ CD24- %B cells showed a statistically significant inverse relationship with the development of MM (p < 0.05, OR <1), whereas IL-1Ra, TNFR1, and memory B-cell %B cells displayed a positive association with the onset of MM (p < 0.05, OR >1). These findings contribute valuable insights to the understanding of the pathogenesis of MM.

Conclusion: This study emphasizes the significant role of inflammatory factors and immune cells in multiple myeloma (MM) progression. IL-1Ra, TNFR1, and memory B-cell percentages are identified as risk factors, while IgD+ CD24- %B cells may protect against progression, suggesting new immunomodulatory treatment strategies. However, research on IgD+ CD24- %B cells and MM is limited, necessitating future studies to clarify their mechanisms and effects on the tumor microenvironment. There is also an urgent need for clinical trials to assess therapies targeting these cells, as well as long-term follow-ups to understand their dynamic changes in relation to disease progression. Further investigation using animal models is warranted to validate their functional role in MM development.

Introduction: The treatment protocols of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) have evolved, with the advent of pediatric-based regimens, measurable residual disease monitoring, and mutation analysis. Among the latter, previous reports have identified FLT-3 mutations in up to 5% of pediatric patients; however, the full clinical significance of these mutations in the non-pediatric population is still uncertain.

Methods: Our cohort includes AYA patients with ALL treated with the NY-II and BFM protocols at different time periods, allowing analysis of prognostic factors and survival outcomes. Additionally, we analyzed DNA samples for FLT-3 mutations, focusing on the potential prognostic implications and treatment responses within our cohort.

Results: No significant differences were found in overall survival or progression-free survival between the two treatment protocols. However, a higher rate of hematopoietic stem-cell transplantation was noted in the NY-II patients. Older age and high WBC count at presentation were identified as adverse prognostic factors using multivariate analysis. FLT-3 mutations were identified in 4 patients (5%) of the cohort, with only 1 patient having FLT-3 internal tandem duplication mutation and 3 patients having FLT-3-tyrosine kinase domain mutations.

Conclusions: The low rate and variability of FLT-3 mutations in an Israeli cohort precludes broad conclusions regarding their prognostic significance. In our cohort, age and WBC count but not treatment protocol or FLT-3 mutations influenced survival.

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction rarely documented in patients with multiple myeloma (MM).

Methods: In our retrospective study of 108 newly diagnosed MM (NDMM) patients from January 2021 to October 2023, we identified 4 cases of DRESS. The clinical characteristics such as clinical manifestations, laboratory results, treatment, and outcome were analyzed.

Results: These patients presented with fever, persistent and recurrent, along with a widespread red rash characterized by diffuse erythematous macules or papules accompanied by intense itching, desquamation, and other dermatological manifestations. Multiorgan involvement was common, including hepatic impairment, acute kidney injury, and type I respiratory failure, alongside pleural effusion and multiple lymphadenopathy. Laboratory findings revealed elevated eosinophil counts, often exceeding 1.5 × 109/L, abnormal liver function tests, acute kidney injury, and inflammatory markers. Anti-MM treatment was promptly suspended, and all patients received corticosteroid therapy. Outcomes varied, with 1 patient succumbing to myeloma progression, another to multiorgan failure, while the remaining 2 patients survived.

Conclusion: In NDMM patients undergoing induction therapy, occurrences of DRESS are infrequent but noteworthy, with an incidence higher than observed in the general population. It presents with significant morbidity and mortality, highlighting the crucial need for early recognition and management.