Expert Review of Hematology最新文献

Introduction: Sickle cell disease (SCD), its treatments and cures present infertility risks. Fertility counseling is broadly indicated for affected girls and women and fertility preservation may appeal to some. Several streams of evidence suggest that the reproductive lifespan of women with SCD is reduced. Pregnancy is associated with high miscarriage rates. There are enduring questions about the effects of highly effective hydroxyurea treatment on female fertility. Current conditioning regimens for gene therapy or hematopoietic stem cell transplant are gonadotoxic. Fertility preservation methods exist as non-experimental standards of care for girls and women. Clinicians are challenged to overcome multifactorial barriers to incorporate fertility counseling and fertility preservation care into routine SCD care.

Areas covered: Here we provide a narrative review of existing evidence regarding fertility and infertility risks in girls and women with SCD and consider counseling implications of existing evidence.

Expert opinion: Addressing fertility for girls and women with SCD requires engaging concerns that emerge across the lifespan, acknowledging uncertainty and identifying barriers to care, some of which may be insurmountable without public policy changes. The contemporary SCD care paradigm can offer transformative SCD treatments alongside comprehensive counselling that addresses fertility risks and fertility preservation opportunities.

Introduction: The therapeutic approach to pain in hemophilia should be multimodal. Intra-articular injections are a good option when joint lesions do not respond to hematological treatment or rehabilitation and orthopedic surgery is not yet indicated. Performing these procedures under ultrasound guidance has been shown to improve their accuracy and efficacy.

Areas covered: This article provides a practical overview of the most frequently employed ultrasound-guided intra-articular procedures on the joints of people with hemophilia. The article describes the key elements for performing the technique on the elbow, knee and ankle as the most affected joints. The particularities of the most frequent indications, arthrocentesis, synoviorthesis and analgesic injections with various products are detailed.

Expert opinion: Current hematological treatments have made it possible to incorporate new therapeutic tools for pain relief for people with hemophilia, including ultrasound-guided joint procedures, which offer excellent results.

Introduction: The treatment of multiple myeloma (MM) is evolving rapidly. Quadruplet regimens incorporating proteasome inhibitors, immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies have emerged as standard-of-care options for newly diagnosed MM, and numerous novel therapies have been approved for relapsed/refractory MM. However, there remains a need for novel options in multiple settings, including refractoriness to frontline standards of care.

Areas covered: Targeting degradation of IKZF1 and IKZF3 - Ikaros and Aiolos - through modulation of cereblon, an E3 ligase substrate recruiter/receptor, is a key mechanism of action of the IMiDs and the CELMoD agents. Two CELMoD agents, iberdomide and mezigdomide, have demonstrated substantial preclinical and clinical activity in MM and have entered phase 3 investigation. Using a literature search methodology comprising searches of PubMed (unlimited time-frame) and international hematology/oncology conference abstracts (2019-2023), this paper reviews the importance of Ikaros and Aiolos in MM, the mechanism of action of the IMiDs and CELMoD agents and their relative potency for targeting Ikaros and Aiolos, and preclinical and clinical data on iberdomide and mezigdomide.

Expert opinion: Emerging data suggest that iberdomide and mezigdomide have promising activity, including in IMiD-resistant settings and, pending phase 3 findings, may provide additional treatment options for patients with MM.

Introduction: Despite clear advancements in the management of classical Hodgkin lymphoma (cHL) over the past decade including better risk stratification, the usage of 18F-flurodeoxyglucose positron emission tomography (FDG-PET)-guided approaches and incorporation of novel agents, approximately one-third of the patients will relapse. Important themes have been recently explored in the first salvage setting including the recognition of the positive prognostic value of a negative pre-autologous stem cell transplantation (ASCT) FDG-PET response and the incorporation of novel agents such as brentuximab vedotin (BV) and immune checkpoint inhibitors (CPIs) as salvage regimens to improve patient outcomes.

Areas covered: The evolving treatment paradigm in optimizing salvage therapy in relapsed refractory cHL (RR-cHL) is discussed, including a vision to the future. The methodology included a literature search on PubMed using keywords. Selected articles were screened and evaluated by the authors of this review.

Expert opinion: Achieving a complete remission by FDG-PET pre-ASCT is the most important prognostic factor in obtaining disease control and subsequent cure, and therefore should be a key goal of any salvage regimen. Although data from randomized controlled trials are currently lacking, retrospective evidence demonstrate superior event free survival with CPI-based regimens compared to conventional chemotherapy or BV-based therapy.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acquired aplastic anemia (acquired AA) in young patients. The objective of the study was to compare patient outcomes after Cyclophosphamide and horse antithymocyte globulin (Cy-hATG) versus Fludarabine-cyclophosphamide and rabbit ATG (Flu-Cy-rATG) as part of conditioning regimen in allo-HSCT for acquired AA.

Research design and methods: Descriptive retrospective study conducted on patients with acquired AA who received allo-HSCT from HLA-matched sibling donors between January 2008 and August 2022 after conditioning regimen with Cy-hATG or Flu-Cy-rATG.

Results: A total of 121 patients were enrolled. Cumulative incidence of graft failure was 11.2% in Cy-hATG and 5.3% Flu-Cy-rATG group. There were no significant differences between the two groups in terms of acute GVHD, chronic GVHD, and transplant related mortality. Flu-Cy-rATG group was associated with significantly higher CMV and EBV reactivation(s) compared to Cy-hATG group (p = 0.008 and 0.035, respectively). After a median follow-up of 58 months, estimated overall survival, event-free survival, and graft rejection-free survival were not statistically different between the two groups.

Conclusions: In high-risk population, Flu-Cy-rATG is associated with comparable outcomes to Cy-hATG in allo-HSCT from MSD. However, it seems to be associated with significant risk of viral infections.

Introduction: Acute pain episodes, also known as vaso-occlusive crises (VOC), are a major symptom of sickle cell disease (SCD) and lead to frequent hospitalizations. The diagnosis of VOC can be challenging, particularly in adults with SCD, 50% of whom have chronic pain. Several potential biomarkers have been proposed for identifying individuals with VOC, including elevation above the baseline of various vascular growth factors, cytokines, and other markers of inflammation. However, none have been validated to date.

Areas covered: We summarize prospective biomarkers for the diagnosis of acute pain in SCD, and how they may be involved in the pathophysiology of a VOC. Previous and current strategies for biomarker discovery, including the use of omics techniques, are discussed.

Expert opinion: Implementing a multi-omics-based approach will facilitate the discovery of objective and validated biomarkers for acute pain.

Introduction: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal.

Areas covered: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects.

Expert opinion: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Background: Platelet storage is complicated by deleterious changes, among which reduction of ristocetin-induced platelet aggregation (RIPA) has a poorly understood mechanism. The study elucidates the mechanistic roles of all the possible players in this process.

Research design and methods: PRP-platelet concentrates were subjected to RIPA, collagen-induced platelet aggregation (CIPA), and flowcytometric analysis of GPIbα and PAC-1 binding from days 0 to 5 of storage. Platelet-poor plasma was subjected to colorimetric assays for glucose/LDH evaluation and automatic analyzer to examine VWF antigen and activity.

Results: From day three of platelet storage, reducing CIPA but not RIPA was correlated with the reduction of both metabolic state and integrin activity. RIPA reduction was directly related to the decreased levels of total-content/expression of GPIbα, and inversely related to its shedding levels during storage. Re-suspension of 5-day stored platelet in fresh plasma compensated CIPA, but not RIPA. VWF concentration and its activity did not change during storage while they had no correlation with RIPA.

Conclusions: This study identified the irreversible loss of platelet GPIbα, but not VWF status, as the primary cause of the storage-dependent decrease of RIPA. Unlike CIPA, this observation was not compensated by plasma refreshment, suggesting that some evidence of PSL may not be recovered after transfusion.