Enhancing the Clinical Management of CMF Through a National Pediatric and Adult Network Based on Biological and Genetic Data

NCT07877727 — Recruiting, 250 participants, Istituto Giannina Gaslini

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Potenziare la Gestione Clinica Delle CMF Attraverso Una Rete Nazionale Pediatrica e Dell'Adulto Basata su Dati Biologici e Genetici / Enhancing the Clinical Management of CMF Through a National Pediatric and Adult Network Based on Biological and Genetic Data

Registry	NCT07877727, acronym 2023-12377081
Status	Recruiting
Study type	Observational
Enrollment	250 (Estimated)
Sponsor	Istituto Giannina Gaslini (Other)
Conditions	Inherited Bone Marrow Failure Syndrome, Fanconi Anemia, Dyskeratosis Congenita, Telomere Biology Disorder, Congenital Neutropenia, Primary Immune Regulatory Disorder, Congenital Amegakaryocytic Thrombocytopenia, Acquired Aplastic Anemia, Paroxysmal Nocturnal Hemoglobinuria, PNH
Dates	start 2025-05-29, primary completion 2026-12-31 (estimated), completion 2026-12-31 (estimated), first posted 2026-10-16, last updated 2026-10-16
Locations	4 sites in Italy

-Summary

A non-profit, translational, prospective and retrospective study.

Patients will be enrolled according to the procedures described in the protocol, and samples will be processed and analyzed as specified in the protocol.

Since constitutional bone marrow failure syndromes (CMF) are rare genetic disorders characterized by a variable and incompletely defined clinical phenotype, a partially unknown genetic etiology, and pathogenetic mechanisms that are only partly understood, we hypothesize that a number of patients currently diagnosed with idiopathic acquired aplastic anemia (AAA) or idiopathic single-lineage/multilineage bone marrow failure (BMF) may have been misdiagnosed and may actually have an underlying CMF.

Therefore, our primary objective is to identify CMF underlying BMF and vice versa, by defining well-characterized patient cohorts based on clinical and family history, clinical manifestations, and immunological findings; identifying disease-specific parameters and biomarkers; and providing disease-specific guidelines to facilitate early diagnosis and, consequently, enable timely and appropriate treatment.

In this context, the use of appropriate artificial intelligence (AI) tools is likely to improve the diagnostic accuracy of this approach.

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+Arms and interventions

Arm	Type	Interventions	Description
Fanconi anemia (FA)			Fanconi anemia (FA)
Dyskeratosis congenita (DC) e altri telomere biology disorders (TBD)			Dyskeratosis congenita (DC) e altri telomere biology disorders (TBD)
Congenital neutropenia (CN)			Congenital neutropenia (CN)
Primary immune regulatory disorders (PIRD)			Primary immune regulatory disorders (PIRD)
Congenital amegakaryocytic thrombocytopenia (CAMT)			Congenital amegakaryocytic thrombocytopenia (CAMT)
Acquired aplastic anemia (AAA), with or without paroxysmal nocturnal hemoglobinuria (PNH)			Acquired aplastic anemia (AAA), with or without paroxysmal nocturnal hemoglobinuria (PNH)

+Outcome measures

Primary outcomes

Early Diagnosis and Molecular Characterization of CMF and AAA [Within the 24-month project period]: To improve the early diagnosis of constitutional bone marrow failure syndromes (CMF) and acquired aplastic anemia (AAA) through the integration of clinical, laboratory, immunological, and genetic data. At least 50 newly enrolled patients will be evaluated prospectively over the first 21 months, alongside approximately 200 previously referred patients analyzed retrospectively using artificial intelligence (AI). The diagnostic work-up will include the implementation of additional tests, such as telomere length assessment by flow-FISH, serum thrombopoietin measurement, and immunophenotyping by flow cytometry. Whole-genome sequencing and functional studies will be used to identify disease-causing variants, copy number variations (CNVs), and clarify variants of uncertain significance (VUS). Early and accurate diagnosis will support appropriate targeted treatment, genetic counseling, surveillance for bone marrow failure and malignancies, and identification of suitable related donors.

+Eligibility

Sex: All, ages: 28 Days to 65 Years

Inclusion Criteria:

* Patients diagnosed with Fanconi anemia (FA), dyskeratosis congenita (DC) and other telomere biology disorders (TBD), congenital neutropenia (CN), primary immune regulatory disorders (PIRD), congenital amegakaryocytic thrombocytopenia (CAMT), and acquired aplastic anemia (AAA), with or without paroxysmal nocturnal hemoglobinuria (PNH).
* Signed informed consent and/or assent obtained from the participant and/or their parents or legal guardians, as applicable.

Exclusion Criteria:

* Absence of signed informed consent and/or assent from the participant and/or their parents or legal guardians

+Locations (4)

Facility	City	Country	Status
AORN San Giuseppe Moscati Hematology and bone marrow Transplant Unit	Avellino	Italy	Recruiting
IRCCS Istituto Giannina Gaslini	Genova	Italy	Recruiting
Azienza Ospedaliera di Rilievo Nazionale Santobono Pausilipon Dipartimento di oncologia, ematologia e terapie cellulari	Naples	Italy	Recruiting
Università degli Studi di Verona Department of Engineering for Innovation Medicine	Verona	Italy	Recruiting