Expert Review of Hematology最新文献

Background: To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM).

Methods: Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes.

Results: This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%).

Conclusions: Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically.

Systematic review registration: PROSPERO: CRD42023420644.

Introduction: The therapeutic landscape for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved over the past decade with dramatically improved outcomes with the introduction of targeted therapies. This unfortunately has not been the case for Richter transformation (RT), the histologic transformation to a more aggressive lymphoma, most typically diffuse large B-cell lymphoma (DLBCL). As such, RT continues to be one of the most challenging complications of CLL/SLL. Historically, RT has a poor response to treatment, with a minority reaching complete remission (CR) and overall survival (OS) being less than a year.

Areas covered: The focus of this review is to discuss the effectiveness of commonly used regimens, and review existing data for emerging regimens being examined in ongoing clinical trials to improve prognosis and outcomes in patients with RT. Despite extensive efforts to optimize therapies for RT, there is still no generalized consensus on either first-line treatment regimens or regimens in the relapsed/refractory setting. RT continues to carry a high mortality rate without durable response to current therapeutic agents.

Expert opinion: Ongoing and future research may identify novel treatment approaches that will eventually improve outcomes for patients with RT. The optimal care for RT patients is a clinical trial, when feasible.

Background: To develop and internally validate a prediction model for identifying patients with hematologic diseases of fall risk.

Research design and methods: This is a prospective cohort study from a prospective collection of data for 6 months. We recruited 412 patients with hematologic diseases in medical institutions and home environment of China. The outcome of the prediction model was fall or not. These variables were filtered via univariable logistic analysis, LASSO, and multivariable logistic analysis. We adopt an internal validation method of K-fold cross validation. The area under the ROC curve and the H-L test were used to evaluate the discrimination and calibration of the model.

Results: Five influencing factors were identified multivariable logistic regression analysis. The established model equation is as follows: the H-L goodness-of-fit test of the model p > 0.05. The area under the ROC curve of train is 0.957 (95% CI: 0.936 ~ 0.978), and the area under the ROC curve of test is 0.962 (95% CI: 0.884 ~ 1), so the model calibration and discriminant validity are good.

Conclusion: Our equation has good sensitivity and specificity in predicting the fall risk of patients with hematologic diseases, and has certain positive significance for clinical assessment of their fall risk.

Trial registration number: ChiCTR2200063940.

Background: Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA).

Research design and methods: We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023.

Results: The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 10⁹/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment.

Conclusions: p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

Introduction: Bystander hemolysis occurs when antigen-negative red blood cells (RBCs) are lysed by the complement system. Many clinical entities including passenger lymphocyte syndrome, hyperhemolysis following blood transfusion, and paroxysmal nocturnal hemoglobinuria are complicated by bystander hemolysis.

Areas covered: The review provides data about the role of the complement system in the pathogenesis of bystander hemolysis. Moreover, future perspectives on the understanding and management of this syndrome are described.

Expert opinion: Complement system can be activated via classical, alternative, and lectin pathways. Classical pathway activation is mediated by antigen-antibody (autoantibodies and alloantibodies against autologous RBCs, infectious agents) complexes. Alternative pathway initiation is triggered by heme, RBC microvesicles, and endothelial injury that is a result of intravascular hemolysis. Thus, C5b is formed, binds with C6-C9 compomers, and MAC (C5b-9) is formulated in bystander RBCs membranes, leading to cell lysis. Intravascular hemolysis, results in activation of the alternative pathway, establishing a vicious cycle between complement activation and bystander hemolysis. C5 inhibitors have been used effectively in patients with hyperhemolysis syndrome and other entities characterized by bystander hemolysis.

Introduction: Immune thrombocytopenia (ITP), a disease that commonly presents with an increased risk of bleeding, can also paradoxically produce an increased risk of thromboembolic events. The risk of thromboembolism can be associated with patient-related factors (e.g. co-morbidities, age and history of thrombosis), disease-related factors (e.g. a greater proportion of younger, more reactive platelets, and the presence of microparticles and pro-inflammatory cytokines) and treatment-related factors (e.g. splenectomy, thrombopoietin receptor agonists, and IVIg).

Areas covered: Aspects of the pathophysiology of ITP and the effects of treatment are discussed with emphasis on individualizing treatment based on the patient's thromboembolic risk, treatment options and preferences.

Expert opinion: An increased understanding of the pathophysiology of ITP has led to the development of new agents such as fostamatinib, a spleen tyrosine kinase inhibitor. Further research into the factors contributing to the risks for bleeding and thromboembolic events can contribute to the development of more specific therapies for ITP and allow greater individualization of therapy based on each patient's medical history and clinical status.

Introduction: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening prothrombotic disorder first identified following the introduction of adenoviral vector vaccines for COVID-19. The condition is characterized by anti-PF4 antibodies and clinically presents with thrombocytopenia and thrombosis often in unusual anatomical sites.

Areas covered: In this review, we discuss the clinical presentation, diagnostic testing, and treatment of VITT. We also review VITT-like syndromes that have been described in patients without previous vaccination. We propose a conceptual framework for the mechanism of anti-PF4 diseases that includes sufficiently high levels of PF4, the presence of a Polyanion that can form immune complexes with PF4, a Pro-inflammatory milieu, and an immunological Predisposition - the 4Ps.

Expert opinion: Significant progress has been made in understanding the characteristics of the VITT antibody and in testing methods that can confirm that diagnosis. Future work should be directed at understanding long-term outcomes, mechanisms of thrombosis, and individual risk factors for this rare but dangerous immune-thrombotic disease.

Introduction: Thrombophilia testing (TT) is a laboratory procedure designed to detect the risk factors involved in the pathogenesis of vascular occlusions. The role of TT is also controversial because it has a limited impact on the choice and duration of antithrombotic treatments.

Areas covered: We reviewed, by examining MEDLINE up to October 2023. Accepted and not accepted thrombophilia markers are discussed along with the appropriateness or not of prescribing TT in several conditions such as: provoked and unprovoked venous thromboembolism (VTE), women who are planning a pregnancy whose relatives had VTE or have a hereditary thrombophilia, before assumption of estro-progestins, after multiple pregnant loss, arterial thrombosis, retinal vein occlusion, and splanchnic vein thrombosis.

Expert opinion: TT is not essential in the management of VTE, but it may be useful for limiting adverse events in case of thrombophilia. We expose our criticism of items afforded by other guidelines by presenting our opinion based on both the scientific evidence and clinical practice. We also deal with common mistakes in prescribing and interpretations of TT hoping to purpose an educational approach on this topic. Finally, we emphasize the creation of the expert in hemostasis and thrombosis who should be present in every hospital.

Background: An accurate assessment of tumor viability after first-line treatment is critical for predicting treatment failure in peripheral T-cell lymphomas (PTCLs). ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) has been adopted as the preferred assessment method in clinical trials, but its impact in clinical practice should be examined. This study aims to determine the prognostic significance of¹⁸F-FDG-PET/CT for survival following first-line treatment in PTCL patients.

Research design and methods: Retrospective observational study including 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites.

Results: Fifty patients were evaluated with¹⁸F-FDG-PET/CT following first-line therapy: 58% were¹⁸F-FDG-PET/CT-negative and 42% were¹⁸F-FDG-PET/CT-positive. Disease progression occurred in 37.9% of¹⁸F-FDG-PET/CT-negative patients and in 80.9% of¹⁸F-FDG-PET/CT-positive patients (p = 0.0037). Median progression-free survival and overall survival were 67 and 74 months for¹⁸F-FDG-PET/CT-negative patients, and 5 (p < 0.0001) and 10 months (p < 0.0001), respectively, in¹⁸F-FDG-PET/CT-positive patients. After multivariate analysis, only B symptoms emerged as a negative predictive factor of complete response (RR 7.08; 95% CI 1.60-31.31; p = 0.001).

Conclusions: ¹⁸F-FDG-PET/CT identifies high-risk PTCL patients who will have poor prognosis and survival following first-line treatment. However, more research is needed to confirm the best treatment options for PTCL patients.