Expert Review of Hematology最新文献

Background: Preterm infants are a group cohort of transfusion recipients due to their low blood volume and underdeveloped hematopoietic system. The objective of this study was to probe the effect of days of age at first blood transfusion on intraventricular hemorrhage (IVH) in very low and extremely low birth weight VLBW and ELBW infants.

Research design and methods: Data of 150 VLBW and ELBW infants receiving blood transfusions were reviewed. IVH and non-IVH groups were established. General data on infants and their mothers and data related to blood transfusion, IVH risk factors, and the predictive value of the relevant factors for IVH were analyzed.

Results: The IVH group had lower birth weight, hemoglobin levels on admission, and days of age at first blood transfusion and higher 5-min Apgar score ≤7 points and early transfusion rate. Spontaneous delivery and 5-min Apgar score ≤7 points were risk factors for IVH. Birth weight and days of age at first blood transfusion had predictive value for IVH in VLBW and ELBW infants.

Conclusions: The younger the days of age at first blood transfusion, the higher the IVH risk. It is necessary to delay the days of age at first blood transfusion and reduce early blood transfusion.

Background: Multiple myeloma (MM) is a plasma cell neoplasm, which accounts for 1-2% of cancers and approximately 17% of hematological malignancies in the United States each year. Fifty percent of patients with symptomatic MM have three or more primary care visits before being referred to a specialist, which is greater than any other cancer. A delay in the diagnosis of multiple myeloma has been shown to negatively impact the clinical course of the disease; patients with longer diagnostic intervals have been shown to experience shorter disease-free survival and higher rates of treatment-related complications.

Research design and methods: We performed a retrospective analysis of patients diagnosed with MM in our institution, to determine the time from the first detectable lab abnormality to the diagnosis of MM.

Results: We included 92 patients in this study. Fifty-two percent of patients had isolated anemia at the time of diagnosis. Twenty-nine percent of patients had a delay in diagnosis of ≥1 year, while 18% had a delay of ≥3 years. Nine patients in our cohort had anemia and an elevated serum total protein (31%). This group had the longest time to diagnosis with a median of 38 months.

Conclusions: Our results did not show any difference in time to diagnosis by race, ethnicity, gender, or socioeconomic status.

Introduction: Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion. Frontline use of intravenous arsenic trioxide (i.v.-ATO) and all-trans retinoic acid (ATRA) has vastly improved cure rates in APL. Researchers in Hong Kong invented the oral formulation of ATO (oral-ATO) and have confirmed a bioavailability comparable to i.v.-ATO. A plethora of studies have confirmed the safety and efficacy of oral-ATO-based regimens in the frontline and relapsed setting.

Areas covered: Aspects on the development of oral-ATO-based regimens for APL in the frontline and relapsed setting are discussed. The short-term and long-term safety and efficacy of oral-ATO-based regimens are discussed. The frontline use of oral-ATO in combination with ATRA and ascorbic acid (AAA) induction in a 'chemotherapy-free' is highlighted.

Expert opinion: Current and ongoing data on the use of oral-ATO-based regimens in APL support the use of oral-ATO as an alternative to i.v.-ATO allowing a more convenient and economical approach to the management of APL.

Introduction: The improved quality of care and increased drug availability have shifted the goal of treating people with hemophilia from life-threatening bleeding prevention to joint health preservation and quality of life amelioration. Many tools are now available to the clinician in order to optimize the management of hemophilic arthropathy.

Areas covered: This paper reviews the pivotal role of ultrasound evaluation in early detection of joint bleeding and differential diagnosis of joint pain, with a focus on the feasibility of a long-term monitoring of joint health through the use of artificial intelligence and telemedicine. The literature search methodology included using keywords to search in PubMed and Google Scholar, and articles used were screened by the coauthors of this review.

Expert opinion: Joint ultrasound is a practical point-of-care tool with many advantages, including immediate correlation between imaging and clinical presentation, and dynamic evaluation of multiple joints. The potential of telemedicine care, coupled with a point-of-care detection device assisted by artificial intelligence, holds promises for even earlier diagnosis and treatment of joint bleeding. A multidisciplinary approach including early intervention by physical medicine and rehabilitation (PMR) physicians and physiotherapists is crucial to ensure the best possible quality of life for the patient.

Introduction: Mantle cell lymphoma (MCL) is an uncommon non-Hodgkin lymphoma that is generally considered incurable. Covalent BTK inhibitors (cBTKi) are the cornerstone of treatment for relapsed or refractory (R/R) MCL, but treatment options are limited and prognosis is poor after cBTKi failure. Pirtobrutinib is a non-covalent BTK inhibitor that has demonstrated excellent efficacy and safety and represents an important new treatment in the evolving treatment landscape of R/R MCL.

Areas covered: This review will provide an overview of the therapeutic landscape of R/R MCL, characteristics of pirtobrutinib, and efficacy and safety data of pirtobrutinib in R/R MCL from pivotal clinical trials. PubMed and major hematology conference proceedings were searched to identify relevant studies involving pirtobrutinib.

Expert opinion: For patients with R/R MCL that has progressed after treatment with cBTKi, pirtobrutinib is an important and efficacious treatment that confers favorable outcomes. In the post-cBTKi setting, when chimeric antigen receptor (CAR) T-cell therapy is not available or feasible, pirtobrutinib is the preferred treatment for R/R MCL. How to sequence or combine pirtobrutinib with CAR T-cell therapy and other available or emerging therapies requires further investigation. Future studies should also explore the role of pirtobrutinib in earlier lines of therapy for MCL.

Introduction: Children receiving treatment for acute myeloid leukemia (AML) are at high risk of invasive fungal disease (IFD). Evidence from pediatric studies support the efficacy of antifungal prophylaxis in reducing the burden of IFD in children receiving therapy for AML, yet existing antifungal agents have specific limitations and comparative data to inform the optimal prophylactic approach are lacking.

Areas covered: This review summarizes the epidemiology of invasive fungal disease (IFD) and current antifungal prophylaxis recommendations for children with acute myeloid leukemia (AML). Challenges with currently available antifungal agents and considerations related to the changing landscape of AML therapy are reviewed. A keyword search was conducted to identify pediatric studies regarding IFD and antifungal prophylaxis in children with AML up to December 2023.

Expert opinion: Children undergoing treatment for AML are recommended to receive antifungal prophylaxis to reduce risk of IFD, with tolerability, pharmacokinetics, feasibility of administration, and drug interactions all factors that require consideration in this context. With increased use of novel targeted agents for AML therapy, together with the development of new antifungal agents, data from well-designed clinical studies to optimize prophylactic approaches will be essential to limit the burden of IFD in this vulnerable cohort.

Introduction: Endogenous DNA damage is a significant factor in the damage of hematopoietic cells. Megakaryopoiesis is one of the pathways of hematopoiesis that ends with the production of platelets and plays the most crucial role in hemostasis. Despite the presence of efficient DNA repair mechanisms, some endogenous lesions can lead to mutagenic alterations, disruption of pathways of hematopoiesis including megakaryopoiesis and potentially result in human diseases.

Areas covered: The complex regulation of DNA repair mechanisms plays a central role in maintaining genomic integrity during megakaryopoiesis and influences platelet production efficiency and quality. Moreover, anomalies in DNA repair processes are involved in several diseases associated with megakaryopoiesis, including myeloproliferative disorders and thrombocytopenia.

Expert opinion: In the era of personalized medicine, diagnosing diseases related to megakaryopoiesis can only be made with a complete assessment of their molecular aspects to provide physicians with critical molecular data for patient management and to identify the subset of patients who could benefit from targeted therapy.

Introduction: Bruton's tyrosine kinaseinhibitors (BTKis) changed the trajectory of upfront and relapsed/refractory chronic lymphocytic leukemia (CLL) treatment. However, BTKis are plagued by a spectrum of toxicities. Zanubrutinib was developed to circumvent challenges with prolonged tolerability by increasing BTK selectivity and maximizing efficacy through pharmacokinetic/pharmacodynamic optimization. However, with the availability of ibrutinib, acalabrutinib, and zanubrutinib, limited data exists to guide sequencing of BTKi therapy in the relapsed/refractory setting.

Areas covered: We review the first head-to-head trial (ALPINE) of zanubrutinib versus ibrutinib for the treatment of relapsed/refractory CLL and compare zanubrutinib's clinical efficacy and toxicities, including in patients with del(17p) and/or TP53 mutations to ibrutinib and acalabrutinib.

Expert opinion: Zanubrutinibrepresents one of the new standards of care for relapsed/refractory CLL based on superior progression-free survival and response rates over ibrutinib. Whilezanubrutinib is associated with fewer cardiac toxicities, similar rates of neutropenia and hypertension are noted. Ongoing studies are pushing the envelope, utilizing targeted drug combinations and minimal residual disease markers as well as receptor tyrosine kinase-like orphan receptor 1 inhibitors, chimeric antigen receptor T-cells, and novel BTK degraders. However, zanubrutinibrepresents a strong contender in the arsenal of treatment options for relapsed/refractory CLL.

Introduction: Artificial intelligence (AI) is a rapidly growing field of computational research with the potential to extract nuanced biomarkers for the prediction of outcomes of interest. AI implementations for the prediction for clinical outcomes for myeloproliferative neoplasms (MPNs) are currently under investigation.

Areas covered: In this narrative review, we discuss AI investigations for the improvement of MPN clinical care utilizing either clinically available data or experimental laboratory findings. Abstracts and manuscripts were identified upon querying PubMed and the American Society of Hematology conference between 2000 and 2023. Overall, multidisciplinary researchers have developed AI methods in MPNs attempting to improve diagnostic accuracy, risk prediction, therapy selection, or pre-clinical investigations to identify candidate molecules as novel therapeutic agents.

Expert opinion: It is our expert opinion that AI methods in MPN care and hematology will continue to grow with increasing clinical utility. We believe that AI models will assist healthcare workers as clinical decision support tools if appropriately developed with AI-specific regulatory guidelines. Though the reported findings in this review are early investigations for AI in MPNs, the collective work developed by the research community provides a promising framework for improving decision-making in the future of MPN clinical care.

Introduction: The combined use of the BCL-2 inhibitor venetoclax with azacitidine now is the standard of care for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy with outcomes exceeding those achieved with hypomethylating agents alone. Venetoclax in combination with intensive chemotherapy is also increasingly used both as frontline as well as salvage therapy. However, resistance to and relapse after venetoclax-based therapies are of major concern and outcomes after treatment failure remain poor.

Areas covered: A comprehensive search was performed using PubMed database (up to April 2024). Studies evaluating venetoclax-based combination treatments in AML and studies assessing markers of response and resistance to venetoclax were investigated. We summarize the status of venetoclax-based therapies in the frontline and relapsed/refractory setting with focus on the main mechanisms of resistance to BCL-2 inhibition. Further, strategies to overcome resistance including combinatorial regimens of hypomethylating agent (HMA) + venetoclax + inhibitors targeting actionable mutations like IDH1/2 or FLT3-ITD and the introduction of novel agents like menin-inhibitors are addressed.

Expert opinion: Although venetoclax is reshaping the treatment of unfit and fit AML patients, prognosis of patients after HMA/VEN failure remains dismal, and strategies to abrogate primary and secondary resistance are an unmet clinical need.