OC 45.1 - Clinical and laboratory assessment of inherited thrombocytopenias predisposing to malignancy in the Spanish Group for Inherited Platelet disorders (GEAPC)

Monday, June 24, 2024

14:45 – 15:00 ICT

Room: 110 A-C

Presenting Author(s)

Ana Marín-Quilez, PhD

PostDoc
Servicio de Hematología y Oncología Médica-HU Morales Meseguer-Centro Regional de Hemodonación-CIBERER-ISCIII-CB15/00055, IMIB-Pascual Parrilla, Universidad de Murcia, Murcia, Spain
Murcia, Murcia, Spain

Co-Author(s)

AR

Agustín Rodríguez-Alen

Hematologist
Servicio de Hematología, Hospital Universitario de Toledo, Toledo, Spain
Toledo, Castilla-La Mancha, Spain
TS

Teresa Sevivas

Hematologist
Blood and Transfusion Service, Universitary Hospitalar Centre, Unidade Local de Saúde de Coimbra, E.P.E., Coimbra, Portugal
Coimbra, Coimbra, Portugal
NR

Nuria Revilla

Hematologist
Department of Hematology, Hospital Universitario Fundación Jiménez Díaz, Health Research Institute-Fundación Jiménez Díaz University Hospital, (IIS-FJD), Madrid, Spain.
Madrid, Madrid, Spain
NB

Nora Butta

Researcher
Grupo de Coagulopatías y Trastornos de la Hemostasia, IdiPaz, Madrid, Spain
Madrid, Madrid, Spain
FF

Francisca Ferrer-marín

Hematologist
Servicio de Hematología y Oncología Médica-HU Morales Meseguer-Centro Regional de Hemodonación-CIBERER-ISCIII-CB15/00055, IMIB-Pascual Parrilla, Universidad Católica de Murcia (UCAM)
Murcia, Murcia, Spain
ML

Mónica López-Duarte

Hematologist
Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain
Santander, Cantabria, Spain
TM

Thais Murciano

Hematologist
Hospital Universitario Vall d'Hebron, Barcelona, Spain
Barcelona, Catalonia, Spain
LM

Laura Murillo-Sanjuán

Hematologist
Hospital Universitario Vall d'Hebron, Barcelona, Spain
Barcelona, Catalonia, Spain
MN

Meritxell Nomdedeu

Hematologist
Hemostasis and Erythropathology LaboratoryHematopathologyDepartment of Pathology, Centre de Diagnostic Biomedic (CDB), Hospital Clinic de Barcelona, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
Barcelona, Catalonia, Spain
ES

Elena Sebastian

Hematologist
Hospital Universitario Infantil Niño Jesús, Madrid, Spain
Madrid, Madrid, Spain
CS

Claudia Serrano

Hematologist
Servicio de Hematología, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
Murcia, Murcia, Spain
Cristina Sierra Aisa, MD

Hematologist
Servicio de Hematología, Hospital Universitario de Cruces, Baracaldo, Spain
Barakaldo, Pais Vasco, Spain
ML

María Luisa Lozano

Hematologist
Servicio de Hematología, Hospital General Universitario Morales Messeguer, Centro Regional de Hemodonación, Universidad de Murcia, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER-ISCIII
Murcia, Murcia, Spain
José M Bastida

Hematologist
Departamento de Hematología, Complejo Asistencial Universitario de Salamanca (CAUSA), Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación del Cáncer, IBMCC-CSIC, Universidad de Salamanca (USAL), Salamanca, Spain. #Grupo Español de Alteraciones Plaquetarias Congénitas (GEAPC).
Salamanca, Castilla y Leon, Spain
José Rivera, PhD

Facultative-Senior investigator
Servicio de Hematología y Oncología Médica-HU Morales Meseguer-Centro Regional de Hemodonación-CIBERER-ISCIII-CB15/00055, IMIB-Pascual Parrilla, Universidad de Murcia, Murcia, Spain.#Grupo Español de Alteraciones Plaquetarias Congénitas (GEAPC) de la SETH
MURCIA, Murcia, Spain

Background: Inherited thrombocytopenia (IT) with germline variants in RUNX1 (RUNX1-RT), ETV6 (ETV6-RT), or ANKRD26 (ANKRD26-RT) carries a high risk (10-45%) of developing hematologic malignancy (IT-HM).

Aims: To assess the clinical, platelet and molecular characteristics of a Spanish cohort of patients diagnosed with IT-HM.

Methods: The GEAPC recruited 305 patients (177 families) with suspected IT. The assessment included clinical background, bleeding, complete blood count, platelet phenotype (platelet aggregation [LTA] and flow-cytometry) and DNA high-throughput sequencing.

Results: Among 217 out of 305 patients (71.1%), 26 types of IT were identified (Table 1). Thirty-five patients (19 families) had RUNX1-RT (16.1%), 19 (6 families) ANKRD26-RT (8.8%), and 8 (4 families) ETV6-RT (3.7%). The median age at genetic diagnosis was 39 [1-74], 33 [0-80], and 30 [4-60] years, respectively. The first cytopenia was detected at 26 [0-60], 15 [0-60] and 12 [1-33] years, respectively. Most patients displayed mild-to-moderate thrombocytopenia and bleeding. Family history of IT was identified in 58% RUNX1-RT, 83% ANKRD26-RT, and 100% ETV6-RT, while malignancy was present in 44%, 50%, and 75%, respectively. Defective LTA (≥1 agonist) was observed in 10/17 (59%), 14/14 (100%), and 2/2 (100%) patients with RUNX1-RT, ANKRD26-RT, and ETV6-RT, respectively. Impaired activation and granule secretion were observed in about 50% of all cases. Most RUNX1-RT patients (78%) exhibited low GPIa levels associated with impaired collagen-induced LTA.
Molecular analysis identified 16 different genetic variants in RUNX1, 4 in ANKRD26, and 4 in ETV6 (Table 1).
Eleven RUNX1-RT (31.4%), 2 ANKRD26-RT (10.5%), and 1 ETV6-RT (12.5%) have developed HM; (median age 48, 53 and 12 years, respectively) (Table 2).

Conclusion(s): In this Spanish IT cohort, the most common form is IT-HM (28.6% of cases). Genetic diagnosis is excessively delayed (10-20 years) compared to the age of first cytopenia identification. The high rate of development of HM (22.5%) reinforces the critical importance of early diagnosis in life.