Investigación hematológica

We are actively engaged in multicenter and investigator-initiated studies focused on bleeding disorders, including hemostasis and thrombotic conditions. One of our key initiatives is ATHN Transcends, a national cohort study designed to evaluate the safety, effectiveness and practice patterns of therapies in participants with congenital or acquired bleeding disorders and connective tissue disorders associated with bleeding tendencies. The study encompasses diverse cohorts, including individuals with hemophilia, von Willebrand disease, congenital platelet disorders, rare bleeding disorders, bleeding not otherwise specified, thrombosis and thrombophilia, and non-neoplastic hematologic conditions. In the area of thrombosis research, we are leading a prospective, randomized, open-label, blinded-endpoint study assessing the efficacy and safety of apixaban for the treatment of venous thromboembolism in patients with cancer.

Our patients also have access to the ATHNdataset, a national database that supports thrombosis and hemostasis research and improves care. It also underpins numerous ATHN studies, such as a recent investigation into the use of direct oral anticoagulants (DOACs) in children. Our research team is studying the efficacy of bridging therapy to provide optimal management for patients with contraindications to anticoagulation. In collaboration with Montefiore Einstein Cardiology, we are also investigating new anticoagulation therapies with new targets and are participating in phase 3 randomized controlled clinical trials evaluating the safety and efficacy of milvexian, an oral factor XIa inhibitor, after a recent acute coronary syndrome and versus apixaban in participants with atrial fibrillation.

Our researchers are also investigating the treatment outcomes of using antithrombotics for various medical and surgical conditions. We recently published data that did not demonstrate a significant difference in incidence of recurrent thromboembolism or bleeding events in patients treated with DOACs and vitamin K antagonists for myeloproliferative neoplasm‐associated thrombosis, as well as data on the efficacy of DOACS in patients with body mass index of more than 35 and after bariatric surgery.

In collaboration with the Department of Anesthesiology, a recent landmark study from the Montefiore Einstein Digital Health Lab analyzed more than 250,000 patients who underwent noncardiac surgical procedures across multiple centers. The study demonstrated that new-onset postoperative atrial fibrillation occurs predictably and increases ischemic stroke risk. The findings suggested that postoperative oral anticoagulation reduced stroke risk during the first year after surgery.

We also reported the clinical and laboratory coagulation characteristics of pediatric and young-adult patients treated for symptomatic COVID‐19 and were instrumental in developing the American Society of Hematology guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.

We are committed to advancing care for patients with myeloproliferative neoplasms (MPNs) through clinical trials aimed at improving disease control and alleviating symptom burden. Some of our research focus is on investigating the outcomes of antithrombotics and novel treatments for MPNs and related complications, developing new therapies for MPNs, studying genetic differences and socioeconomic determinants of myelofibrosis outcomes and exploring the translational application of immune modulation in stem cell transplantation. Ongoing studies include a phase 3 trial evaluating navtemadlin as an adjunct to ruxolitinib in JAK inhibitor-naive patients with myelofibrosis who exhibit a suboptimal response to initial therapy. We are also leading a phase 2 study focused on providing long-term safety data on momelotinib in patients with primary myelofibrosis.

In polycythemia vera, a phase 3 trial is under way evaluating the safety and efficacy of rusfertide for maintaining hematocrit control and improving symptomatology, and in essential thrombocythemia, we are conducting a phase 2 single-arm study assessing the efficacy and safety of ropeginterferon alfa-2b-njft in adult patients. Furthermore, we are participating in a national multicenter observational study enrolling patients suspected or newly diagnosed with myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap disorders or idiopathic cytopenia of undetermined significance. Participants in this study are followed longitudinally, with clinical data, blood and tissue samples collected to establish a comprehensive biorepository aimed at facilitating research into the natural history and progression of MDS.

We recently participated in an observational, multicenter international study—part of a European LeukemiaNet project—aimed at estimating the incidence and risk factors for thrombotic and bleeding complications in MPN patients with atrial fibrillation and venous thromboembolism who are treated with a DOAC in real-world clinical practice.

We also published real-world outcomes of ruxolitinib treatment for polycythemia vera and found that crizotinib (a tyrosine kinase receptor inhibitor) has preclinical efficacy in Philadelphia chromosome-negative myeloproliferative neoplasms, suggesting that crizotinib should be investigated for the treatment of MPN patients. We recently published the final results of a phase 2 study of add-on parsaclisib, a PI3Kδ inhibitor, for patients with myelofibrosis and suboptimal response to ruxolitinib and found that parsaclisib reduced spleen volume and improved symptom scores when added to ruxolitinib for patients with myelofibrosis.

Through observational registries and interventional trials, we aim to optimize treatment strategies and improve outcomes for individuals living with SCD. Our clinical research spans interventional studies and real-world outcomes analyses, including an evaluation of healthcare utilization patterns in patients with SCD and their association with sickle cell retinopathy—offering important insights into the broader systemic burden of the disease.

Ongoing clinical trials include a phase 1/2 trial investigating the safety and efficacy of intravenous immune globulin for the acute treatment of pain crises in SCD. We are also conducting a phase 3, multicenter, randomized, placebo-controlled, double-blind study assessing the efficacy and safety of crizanlizumab versus placebo, with or without hydroxyurea or hydroxycarbamide therapy, in adolescent and adult patients with frequent vaso-occlusive crises.

Our program includes key clinical trials of etavopivat, an investigational oral small-molecule activator of erythrocyte pyruvate kinase. In the FLORAL study, we are evaluating the long-term safety and efficacy of etavopivat in individuals with SCD or thalassemia. Additionally, we are leading the HIBISCUS study, a phase 2/3 trial evaluating the efficacy and safety of etavopivat, testing its ability to improve hemoglobin levels and reduce the frequency of vaso-occlusive crises compared to placebo in adults and adolescents with SCD.

Complementing these interventional research efforts, the WeDecide study is a large observational investigation comparing the long-term outcomes of matched related donor hematopoietic stem cell transplantation versus nontransplant disease-modifying therapies in pediatric patients with SCD. We are also participating in a multicenter study designed to assess the safety, effectiveness and pharmacokinetics of CSL889 (human hemopexin) administered intravenously to adults and adolescents with SCD experiencing vaso-occlusive crises.

Our Immunohematology Research Program is actively evaluating the safety and efficacy of a variety of novel therapies for the treatment of immune-mediated hematologic conditions, with a particular focus on warm autoimmune hemolytic anemia (wAIHA), immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). We are studying B-cell-activating factor inhibitors as a potential immunomodulatory therapy in wAIHA and recently published the results from a phase 2 open-label study of parsaclisib for the treatment of primary autoimmune hemolytic anemia (AIHA).

Current studies include a phase 2/3 trial evaluating the efficacy and safety of M281, a fully human, antineonatal Fc receptor (FcRn) inhibitor, in participants with wAIHA, a phase 3 study comparing ianalumab to placebo in patients with wAIHA who have failed at least one prior therapy.  We are also conducting a phase 3 trial assessing the safety and efficacy of iptacopan, a factor B inhibitor, in complement-inhibitor-naive adult patients with aHUS and a phase 3 trial characterizing the long-term safety and tolerability of iptacopan in patients with paroxysmal nocturnal hemoglobinuria.

In the area of ITP, we are leading a phase 3 trial evaluating rilzabrutinib, an orally administered Bruton tyrosine kinase inhibitor, for adults and adolescents with persistent or chronic ITP. Additional research includes a phase 3 study evaluating the combination of ianalumab and eltrombopag in patients with primary ITP who have failed corticosteroid therapy.

We are leading collaborative intravenous (IV) iron therapy research and pioneered one of the first programs of its kind—the e-IRON Program—a telemedicine referral platform developed for triaging and expediting the management of patients with iron deficiency and iron deficiency anemia (IDA) who require IV iron infusion. We have conducted several studies evaluating the feasibility, efficacy and efficiency of e-IRON and are also actively participating in clinical trials studying the safety and efficacy of various IV iron formulations for IDA.

Our pediatric specialists participated in the multicenter clinical trial that led to the expanded FDA approval of Injectafer®, an IV ferric carboxymaltose, to include pediatric patients one year of age and older with IDA who have an inadequate response to oral iron therapy. We are also actively participating in a phase 3 randomized, multicenter, multinational study to evaluate the safety, efficacy and pharmacokinetics of ferumoxytol or IV iron infusion in comparison to iron sucrose (Venofer®) for the treatment of IDA in pediatric subjects with chronic kidney disease.

A recent meta-analysis conducted by our Cardiology Division showed that IV iron–carbohydrate complex therapy in patients with iron deficiency and heart failure with reduced ejection fraction was beneficial in lowering the risk of hospitalization due to heart failure.

From our initial study of the pilot e-IRON Program, our research revealed that by dispensing with the need for a face-to-face Classical Hematology visit, e-IRON simplifies the process of referral for IV iron across a broad range of indications and significantly reduces the time required from referral to infusion scheduling, accelerating the administration of IV iron when appropriate. Roughly 2% (2/81) of cases where IV iron was indicated required in-person, face-to-face appointments.

Results from 477 unique consults from more than a year of experience with the e-IRON platform verified the feasibility and efficiency of a telemedicine approach in expediting the management of patients requiring IV iron. In a study of 239 pregnant women who were referred to the e-IRON Program, our researchers found that e-IRON facilitates rapid triage and treatment of anemic pregnant patients requiring IV iron and that the earlier the infusion is administered, the greater the increment in hemoglobin level, underscoring the value of a protocol that minimizes the time interval between referral and infusion. Of 958 referrals to the e-IRON Program in 2023, IV iron was approved in roughly two-thirds of the cases, and a traditional face-to-face encounter was recommended in 3% of the cases.

From an analysis of 266 women of reproductive age with IDA who were referred for consideration for IV iron via e-IRON, our data provided evidence that the pathological role of heavy menstrual bleeding was underrecognized, resulting in high recurrence rates of IDA. As a result of this research, we modified our e-IRON protocol to include routine screening for a history of heavy menstrual bleeding at the time of the iron infusion and have instituted an expedited referral pathway to gynecology providers when necessary.

Together, these studies underscore our commitment to advancing both the science and delivery of IV iron therapy. By combining clinical research, real-world implementation and data-driven protocol refinement, we continue to improve outcomes for patients with IDA across the lifespan.

Our research program is dedicated to advancing the understanding of blood disorders in women across the reproductive lifespan. Key areas of investigation include maternal hematologic conditions, fetal and neonatal outcomes of pregnancy, and the lived experiences of women managing chronic hematologic disease. We have examined pain frequency and healthcare utilization patterns among women with SCD experiencing menstruation-associated pain crises, underscoring the importance of improving access to effective treatment options. In a study of North American physician practice patterns in the management of anticoagulation during pregnancy, we found that clinical responses to commonly encountered thrombophilia scenarios were not always consistent with published guidelines. Additionally, we reported the findings from the first multicenter international cohort study evaluating AIHA during pregnancy and the puerperium, contributing essential data to an underexplored area of maternal hematology and its implications for both maternal and fetal outcomes.