Pediatric bone marrow failure: Clinical, hematological and targeted next generation sequencing data

Area of Science:

• Pediatric Hematology
• Genetics
• Oncology

Background:

• Bone marrow failure (BMF) syndromes in children present complex diagnostic challenges.
• Understanding the genetic underpinnings is crucial for accurate diagnosis and prognosis.

Purpose of the Study:

• To evaluate the clinico-hematological, genetic, and outcome profiles of children with BMF.
• To delineate the genotype and phenotype in pediatric BMF.
• To identify causative mutations in inherited bone marrow failure syndromes (IBMFS) and investigate outcomes in aplastic anemia.

Main Methods:

• Retrospective analysis of children with suspected IBMFS (Group 1) and idiopathic aplastic anemia (IAA) treated with immunosuppressive therapy (IST) (Group 2).
• Targeted next-generation sequencing (NGS) and whole-exome sequencing (WES) were performed on a subset of patients.
• Clinico-hematological data and treatment responses were assessed.

Main Results:

• Causative mutations were identified in 55.5% of Group 1 and 13.3% of Group 2 patients.
• In Diamond-Blackfan anemia (DBA), mutations in RPS 19 and RPL5 genes were common.
• Phenotypic abnormalities were noted in 69.5% of IBMFS cases, with 68.4% responding to steroids. In IAA, overall response to IST was 51%, with 3-year overall survival (OS) and failure-free survival (FFS) of 68% and 48%, respectively.

Conclusions:

• Genetic testing is valuable for diagnosing IBMFS in children.
• Targeted sequencing can detect germline mutations in UBMFS and IAA.
• This study provides insights into the genetic landscape and clinical outcomes of pediatric BMF, informing management strategies.