Multidisciplinary Study Evaluates Prevalence of Hematologic Malignancies in Familial Platelet Disorder

A study of patients who have familial platelet disorder with associated myeloid malignancy (FPDMM) showed that 17% had hematologic malignancies, including myelodysplastic syndromes (MDS).

Paul Liu, MD, PhD, of the National Human Genome Research Institute at the National Institutes of Health, and colleagues conducted the research and published their findings in Blood.

They conducted the natural history study because FPDMM, which is caused by deleterious germline RUNX1 variants, is “characterized by thrombocytopenia, platelet functional defects, and predisposition to hematologic malignancies.”

Dr. Liu and colleagues enrolled 214 participants in the study, including 111 patients with 39 different RUNX1 variants from 45 unrelated families.

In the patients who had available data, 91% (70 of 77) had thrombocytopenia, 100% (18 of 18) had abnormal platelet aggregometry, 46% (16 of 35) had platelets with decreased dense granules, and 51% (28/55) had abnormal bleeding scores.

In the 55 patients who had histologic evaluation of nonmalignant bone marrow, 22% had an increased number of megakaryocytes, and 76% had dysmegakaryopoiesis. The researchers reported that 55% of adult patients had reduced cellularity for age, while 81% of the 21 pediatric cases evaluated had reduced cellularity for age.

Of the patients with available data on allergic and gastrointestinal conditions, 92% (42 of 45) had allergic symptoms and 80% (24 of 30) had gastrointestinal symptoms.

Of the 111 patients enrolled, 17% were diagnosed with hematologic malignancies, including MDS, acute myeloid leukemia, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and smoldering myeloma.

Nearly all (94.7%) of patients with hematologic malignancies were relapsed or refractory to upfront therapy and were referred for hematopoietic stem cell transplantation, according to the study’s authors.

Furthermore, most of the 45 families (65%) had at least one family member who developed a hematologic malignancy.

“Our results highlight the importance of a multidisciplinary approach, early malignancy detection, and wider awareness of inherited disorders,” Dr. Liu and colleagues concluded. “This actively accruing, longitudinal study will genotype and phenotype more patients with FPDMM, which may lead to better understanding of the disease pathogenesis and clinical course, which may then inform preventative and therapeutic interventions.”

Reference

Liu PP, Cunningham L, Merguerian MD, et al. Natural history study of patients with familial platelet disorder with myeloid malignancy. Blood. 2023. doi:10.1182/blood.2023019746