Natural history study of patients with familial platelet disorder with associated myeloid malignancy
Year: 2023
Type: article
Study design: Observational Study
Abstract: ABSTRACT: Deleterious germ line RUNX1 variants cause the autosomal dominant familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematologic malignancies (HMs). We launched a FPDMM natural history study and, from January 2019 to December 2021, enrolled 214 participants, including 111 patients with 39 different RUNX1 variants from 45 unrelated families. Seventy of 77 patients had thrombocytopenia, 18 of 18 had abnormal platelet aggregometry, 16 of 35 had decreased platelet dense granules, and 28 of 55 had abnormal bleeding scores. Nonmalignant bone marrows showed increased numbers of megakaryocytes in 12 of 55 patients, dysmegakaryopoiesis in 42 of 55, and reduced cellularity for age in 30 of 55 adult and 17 of 21 pediatric cases. Of 111 patients, 19 were diagnosed with HMs, including myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and smoldering myeloma. Of those 19, 18 were relapsed or refractory to upfront therapy and referred for stem cell transplantation. In addition, 28 of 45 families had at least 1 member with HM. Moreover, 42 of 45 patients had allergic symptoms, and 24 of 30 had gastrointestinal (GI) symptoms. Our results highlight the importance of a multidisciplinary approach, early malignancy detection, and wider awareness of inherited disorders. This actively accruing, longitudinal study will genotype and phenotype more patients with FPDMM, which may lead to a better understanding of the disease pathogenesis and clinical course, which may then inform preventive and therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT03854318.
Source: Blood
Authors: Lea Cunningham, Matthew Merguerian, Katherine R. Calvo, Joie Davis, Natalie T. Deuitch, Alina Dulau-Florea, Nisha Patel, Kai Yu, Keith Sacco, Sumona Bhattacharya, Monica Passi, Neval Ozkaya, Seila De Leon, Shawn Chong, Kathleen Craft, Jamie Diemer, Erica Bresciani, Kevin O’Brien, Elizabeth J. Andrews, Nguyen Park, Londa Hathaway, Edward W. Cowen, Theo Heller, Kerry Ryan, Amisha Barochia, Khanh Nghiem, Julie Niemela, Sergio Rosenzweig, David J. Young, Pamela A. Frischmeyer-Guerrerio, Raul Braylan, Paul P. Liu
Institutions: National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, Johns Hopkins University, Johns Hopkins Medicine, National Institutes of Health Clinical Center, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Heart, Lung, and Blood Institute
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Clinical Center
OpenAlex ID: W4386949145