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.

Background: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are novel chimeric antigen receptor (CAR)-T cell therapies targeting B-cell maturation antigen (BCMA), and both have recently gained approval by the US Food Drug Administration (FDA) for the treatment of relapsed and refractory multiple myeloma (RRMM).

Summary: These therapies offer unprecedented responses in RRMM but present new challenges including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, cytopenias, infections, and hypogammaglobulinemia.

Key messages: In the evolving CAR-T landscape, a primary objective is to develop innovative strategies for managing associated toxicities. Through meticulous exploration of underlying mechanisms and tailored interventions, we aim to enhance safety and enable broader outpatient utilization. Refinement of protocols, biomarker identification, and robust monitoring are imperative for sustained efficacy. This comprehensive approach guarantees the continuous advancement and optimization of CAR-T therapy.

Introduction: We aimed to identify the clinical characteristics and risk factors for chronic immune thrombocytopenia (ITP) in patients with systemic lupus erythematosus (SLE).

Methods: We retrospectively reviewed patients diagnosed with SLE-associated ITP between January 2000 and December 2021. Patient characteristics were analyzed according to the progression of chronic thrombocytopenia. No response was defined as a platelet count <30 × 109/L or less than double the baseline count after treatment. Factors associated with chronic ITP were evaluated by logistic regression analysis.

Results: Among the 121 patients with SLE-associated ITP, 27 progressed to chronic ITP lasting more than 1 year after initial diagnosis. The median initial platelet count was significantly lower in patients with chronic thrombocytopenia than in those without the disease (16 vs. 51 × 109/L). Patients who did not achieve a response within 1 month of treatment exhibited a high probability of progressing to chronic ITP (55.6 vs. 22.3%, p < 0.001). Multivariable analysis revealed that severe thrombocytopenia at baseline (<20 × 109/L) (adjusted odds ratio [aOR] = 13.628, 95% confidence interval [CI] = 3.976-46.791) and no response within 1 month (aOR = 9.171, 95% CI = 2.776-30.298) were significantly associated with the risk of progression to chronic ITP in patients with SLE. Approximately one-quarter of the patients with SLE-associated ITP progressed to chronic ITP.

Conclusion: Severe thrombocytopenia and failure to achieve a response within 1 month were risk factors for the development of chronic ITP in those patients.

Introduction: Treatment of patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) remains a significant clinical challenge. Many new strategies are changing the treatment landscape of r/r BCP-ALL in recent years. Blinatumomab has improved outcomes in r/r BCP-ALL, though high treatment costs and extended hospital stays are significant concerns. We considered that shortening the duration of blinatumomab administration during induction therapy might solve these problems.

Methods: We retrospectively analyzed 19 patients with r/r BCP-ALL treated with different durations of blinatumomab, where 10 patients received blinatumomab for 14 days (Bli 14D group) and 9 received it for a longer duration (LT group, 21-28 days).

Results: The overall response rate (ORR) was 63.2% (12/19) of patients in total, and the ORRs in 14D and LT groups were almost the same (60% and 66.6%, respectively). The median overall survival was not reached in either groups. The median event-free survival time was 4.1 months in LT group and not reached in D14 group. The most common adverse events were consistent with previous reports, including cytokine release syndrome, neurologic toxicity, and hematological toxicity.

Conclusion: A 14-day blinatumomab administration may be a promising and well-tolerated regimen in r/r BCP-ALL, offering the same ORR and survival rates.

Introduction: Acute myeloid leukemia (AML) is a heterogenous hematologic malignancy that maintains high relapse rates and poor survival despite ongoing treatment advances. There is critically unmet need for consistently providing long-term survival with minimal treatment toxicity for AML patients. Advances in artificial intelligence/machine learning (AI/ML) offer new approaches to addressing clinical challenges in AML.

Methods: In this systematic narrative review, 426 publications focusing on the intersection of AML and AI/ML between January 1, 2010, and July 30, 2024, are reviewed.

Results: The evolution of AI/ML tools over time is described from a clinically relevant perspective with a distinction between early epochs of AI/ML versus more contemporary algorithms, such as generative adversarial networks and transformer-based algorithms. This review highlights the utilization of contemporary AI/ML algorithms via addressing diagnostic challenges, molecular risk stratification problems, and clinical outcome prediction in the context of AML.

Conclusion: Overall, AI/ML represents a promising new frontier in approaching clinical problems in AML, though there are still opportunities for utilization, particularly in the setting of allogeneic stem cell transplantation.

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: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide [Gut Liver. 2017;11(1):27-37]. The use of PPI has become a common practice and is overprescribed for all patients with cancer including patients with hematological malignancies. In the current study, we aimed to explore retrospectively the effect of PPI, on time to first treatment (TTFT) in a large cohort of patients with chronic lymphocytic leukemia (CLL) who were under watch-and-wait approach.

Methods: The cohort is based on anonymized data obtained from electronic medical records of Maccabi Healthcare Services (MHS) members, who is the second-largest healthcare organization in Israel, with 2.5 million insured patients, and received a diagnosis of CLL during this period.

Results: Our cohort included 3,474 patients with CLL who are treatment-naïve, and the median follow-up was 1,745 days (602-3,700). A total of 1,061 patients (30.5%) received a PPI agent, for a minimum of 3 months during the watch-and-wait period. The intake of PPI was found to be associated with a shorter TTFT: among PPI users, the 10-year treatment-free ratio is 79.2%, while among non-PPI users it is 90.6%.

Conclusion: Routine use of PPI in CLL patients may negatively impact their clinical course. Biology of this primary observation requires further investigation.