100 results match your criteria: "Center for Blood Disorders[Affiliation]"

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of aggressive large B-cell lymphoma (aLBCL). Patients with transformed indolent non-Hodgkin lymphoma (tiNHL) were included in key CAR trials, but outcomes of CAR for this distinct, historically high-risk group are poorly understood. We conducted a multicenter retrospective study of 1182 patients with aLBCL receiving standard-of-care CAR T between 2017 and 2022, including 338 (29%) with tiNHL.

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Article Synopsis
  • Bruton tyrosine kinase inhibitors (BTKi) have significantly improved treatment for B-cell malignancies, but many patients stop using them due to side effects, with cardiac issues being the most common reason for discontinuation.* -
  • The BRUIN study tested pirtobrutinib, a new non-covalent BTKi, on 127 patients who were intolerant to previous BTKi treatments, finding that many experienced fewer or no cardiac issues while showing a high overall response rate.* -
  • Results indicated pirtobrutinib had a median time on treatment of 15.3 months, with notable side effects like fatigue and neutropenia; overall, it proved to be a safe and effective alternative for
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Neurosurgical bleeding in platelet storage pool disorder: a case report.

Platelets

December 2024

Division of Hematology, and Washington Center for Bleeding Disorders, University of Washington, Seattle, WA, USA.

Dense-granule deficiency (DGD) is an inherited platelet disorder due to the absence of dense granules essential for activation of platelets in the event of vascular injury. Decreased platelet dense granules can be detected by electron microscopy, while other tests of hemostasis, including platelet function analyzer (PFA®) closure times, may be normal. The present case report describes a patient with a lifelong history of mucocutaneous bleeding and excessive hemorrhage with resection of vestibular Schwannoma.

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Article Synopsis
  • Pirtobrutinib is a new reversible drug that targets Bruton tyrosine kinase, showing effective results in treating B-cell malignancies with low patient dropout and dose reduction rates.
  • A study from the BRUIN trial evaluated the safety of pirtobrutinib in patients who were treated for 12 months or more, revealing common side effects like fatigue and diarrhea, with most adverse events occurring in the first year of treatment.
  • Overall, the findings suggest that pirtobrutinib has a favorable safety profile for long-term use, with no new significant toxicity concerns reported.
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To address acute vaso-occlusive episodes (VOEs), the leading cause of emergency department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, ALIGN (An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD), across 8 sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers.

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Bispecific antibodies (BsAb) that target CD3 and CD20 represent a new milestone in the treatment of patients with B-cell non-Hodgkin lymphoma. These drugs have demonstrated remarkable single-agent activity in patients with heavily pretreated disease, and 3 drugs have so far received regulatory approvals in various countries. However, BsAbs can potentially lead to severe toxicity associated with T-cell activation, particularly cytokine release syndrome (CRS).

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Hydroxyurea reduces sickle cell disease (SCD) complications, but medication adherence is low. We tested 2 mobile health (mHealth) interventions targeting determinants of low adherence among patients (InCharge Health) and low prescribing among providers (HU Toolbox) in a multi-center, non-randomized trial of individuals with SCD ages 15-45. We compared the percentage of days covered (PDC), labs, healthcare utilization, and self-reported pain over 24 weeks of intervention and 12 weeks post-study with a 24-week preintervention interval.

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Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia.

N Engl J Med

July 2023

From Memorial Sloan Kettering Cancer Center (A.R.M.), and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center (N.L.), New York, the Donald and Barbara Zucker School of Medicine, Northwell-Hofstra, Uniondale (J.M.R.), Northwell Health Cancer Institute at Lake Success, North New Hyde Park (J.M.R.), and the Lymphoma Section, Department of Medical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo (F.H.-I.) - all in New York; the Ohio State University Comprehensive Cancer Center, Columbus (J.A.W.), and Cleveland Clinic, Cleveland (D.J.) - both in Ohio; Dana-Farber Cancer Institute and Harvard Medical School - both in Boston (J.R.B.); Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan (P.G.), and IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli" (P.L.Z.), and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna (P.L.Z.), Bologna - all in Italy; the Center for Blood Disorders and Cellular Therapy, Swedish Cancer Institute (K.P.), and the Fred Hutchinson Cancer Center, University of Washington (C.S.U.) - both in Seattle; Oxford University Hospitals NHS Foundation Trust, Churchill Cancer Centre, Oxford (T.A.E.), and the Department of Haematology, St. James's University Hospital, Leeds (T.M.) - both in the United Kingdom; the Institute of Hematology and Transfusion Medicine, Warsaw (E.L.-M.), and Maria Sklodowska-Curie National Research Institute of Oncology, Krakow (W.J.) - both in Poland; Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the University of Melbourne, Melbourne, VIC (C.S.T., J.F.S.), and Linear Clinical Research and Sir Charles Gairdner Hospital (C.Y.C.), and the Medical School, University of Western Australia (C.Y.C.), Perth, WA - all in Australia; Medical College of Wisconsin, Milwaukee (N.N.S.); University of North Carolina at Chapel Hill, Chapel Hill (C.C.C.); the University of California, San Francisco, San Francisco (B.F.); Florida Cancer Specialists, Sarah Cannon Research Institute, Sarasota (M.R.P.), and the Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami (A.J.A.) - both in Florida; Winship Cancer Institute, Emory University, Atlanta (J.B.C.); the Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia (J.N.G.); Sarah Cannon Research Institute, Nashville (I.W.F.); Robert H. Lurie Comprehensive Cancer Center, Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago (S.M.); Loxo@Lilly (M.B., B.N., P.A., D.W., D.E.T.) and Eli Lilly (C.W., A.S.R.) - both in Indianapolis; and M.D. Anderson Cancer Center, Houston (W.G.W.).

Article Synopsis
  • Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) often struggle after failing treatment with covalent BTK inhibitors, prompting the need for new options like pirtobrutinib, a selective noncovalent BTK inhibitor designed to resume BTK inhibition.* -
  • In a phase 1-2 trial involving 317 patients, 73.3% responded positively to pirtobrutinib, with a notable 82.2% response rate when including those showing partial responses with lymphocytosis; the median progression-free survival was reported at 19.6 months.* -
  • Common side effects from pirtobrutinib treatment included infections (71%),
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Article Synopsis
  • Pirtobrutinib is a new, selective Bruton tyrosine kinase inhibitor (BTKi) that shows promise for patients with mantle-cell lymphoma (MCL) who have previously been treated with covalent BTK inhibitors due to a generally poor prognosis.
  • In a phase I/II trial, the drug demonstrated an overall response rate of 57.8% with a median duration of response lasting 21.6 months, indicating effectiveness in this challenging patient group.
  • The treatment was well tolerated, with only a small percentage of patients discontinuing therapy due to adverse events such as fatigue and diarrhea, suggesting it may be a viable option for patients with previously recurRent MCL.
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Follicular lymphoma (FL) is the second most common lymphoma in the United States and is characterized by a variable clinical course, disease heterogeneity, and a relapse-and-remittance pattern historically accompanied by successive shortening of clinical response with every line of treatment. Factors such as progression of disease within 24 months of initial treatment are associated with poor survival outcomes. Although rituximab-based regimens are preferred for early lines of treatment, no clear standard of care exists for treatment of FL in the third-line setting or later as approved third-line treatments have not been compared in a prospective, randomized clinical trial.

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Chimeric antigen receptor T-cell therapy (CART) has extended survival of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). However, limited durability of response and prevalent toxicities remain problematic. Identifying patients who are at high risk of disease progression, toxicity, and death would inform treatment decisions.

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Article Synopsis
  • * Data from 11 heavily pretreated patients indicate that selinexor (X) regimens show strong effectiveness and produce lasting responses, even when used later in treatment.
  • * X-containing regimens resulted in better overall response rates and longer progression-free survival compared to previous anti-BCMA treatments, highlighting their potential in addressing an ongoing treatment gap.
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  • A phase 3 clinical trial assessed the safety and effectiveness of rivipansel, an E-selectin antagonist, in 345 patients (adults and children) with vaso-occlusive crises (VOC) requiring hospitalization.
  • The study found that rivipansel did not significantly improve the primary endpoint of time to readiness for discharge compared to placebo, although it did notably reduce soluble E-selectin levels in the treatment group.
  • A post hoc analysis suggested that administering rivipansel early after VOC pain onset could significantly decrease the time to discharge and reduce opioid use, indicating that the timing of treatment may be key for better outcomes.
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Caring for children and adolescents with disorders of hemostasis and thrombosis (HAT) has become more specialized and requires a unique skill set that many providers are not able to obtain in standard pediatric hematology/oncology/bone marrow transplant fellowship training programs. The influx of numerous therapeutic advances and increasing medical complexity has expanded the need for experienced HAT providers and subspecialty collaboration in the inpatient setting due to the nuances in the management of patients with HAT complications and concerns. While there are data highlighting the benefits of an inpatient hemostasis, thrombosis, and anticoagulation management service in adult hospitals, there are limited pediatric data supporting such programs.

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  • Preclinical studies showed that combining an anti-PD-1 inhibitor with a CDK9 inhibitor can boost cancer-fighting effects while minimizing side effects, indicating a potential new treatment strategy.
  • The phase 1 KEYNOTE-155 trial tested this combination on patients with difficult-to-treat cancers like chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and multiple myeloma, focusing on safety and effectiveness.
  • Out of 72 patients, the combination treatment was generally well tolerated, with observed response rates of 29.4% for chronic lymphocytic leukemia and 21.1% for diffuse large B-cell lymphoma, but no responses in multiple myeloma, highlighting a need for further research on this combination therapy
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Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R-CHOP) in newly diagnosed high-risk DLBCL.

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The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes.

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Purpose: CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL).

Methods: Previously untreated CLL patients age < 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax.

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Pulmonary hypertension (PH) is a progressive cardiovascular disorder in which local vascular inflammation leads to increased pulmonary vascular remodeling and ultimately to right heart failure. The HDAC inhibitor butyrate, a product of microbial fermentation, is protective in inflammatory intestinal diseases, but little is known regarding its effect on extraintestinal diseases, such as PH. In this study, we tested the hypothesis that butyrate is protective in a Sprague-Dawley (SD) rat model of hypoxic PH.

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Current and future treatment strategies in chronic lymphocytic leukemia.

J Hematol Oncol

April 2021

Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, 1221 Madison St, Seattle, WA, 98104, USA.

Treatment decisions for patients with chronic lymphocytic leukemia (CLL) are dependent on symptoms and classification into high-, medium-, or low-risk categories. The prognosis for CLL hinges, in part, on the presence or absence of less-favorable genetic aberrations, including del(17p), del(11q), TP53 dysfunction, and IGHV mutations, as these markers are associated with worse treatment response. Promising results from multiple clinical trials show emerging therapies targeting Burton tyrosine kinase, B-cell leukemia/lymphoma 2, and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta result in better outcomes and prolonged progression-free survival for patients both with and without certain high-risk aberrations.

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Treatment selection in patients with relapsed or refractory follicular lymphoma.

Clin Adv Hematol Oncol

December 2020

Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, Washington.

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In patients with follicular lymphoma, the prolonged clinical course consisting of multiple relapses is a fundamental challenge that requires clinicians to consider how to best balance treatment efficacy while minimizing toxicity and preserving quality of life. The treatment approaches and decisions regarding therapy are largely driven by the unique clinical features evident in each patient. The traditional treatment approaches for relapsed follicular lymphoma include chemoimmunotherapy regimens, targeted agents, radioimmunotherapy, and, occasionally, immunotherapy alone.

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