Familial Patterns in Acute Lymphoblastic Leukemia: Lessons From Three Siblings

Acute lymphoblastic leukemia is a sporadic condition and has been reported to be familial in less than 5% of cases. Here, we present the clinical, genetic, treatment, and pathologic features of three siblings with precursor B acute lymphoblastic leukemia by the order of occurrence, suggesting a potential involvement of germline mutations in the pathogenesis of the disease. Their parents denied consanguinity as well as any familial history of syndromic diseases or neoplasms. Cases 1 and 2 have experienced a relapse after achieving remission, and case 3 has been diagnosed in recent years. Recurrent cytogenetic abnormalities shared across Cases 2 and 3 raised the hypothesis that monosomy 20 may be a susceptible marker in familial B-ALL. HLAs were fully matched for Cases 2 and 3; so, Case 3 donated stem cells to his older brother (Case 2) 3 months before his own involvement. Today, these cases are in complete remission of the disease. This study supports genetic counseling and targeted germline testing in familial ALL cases and argues for cautious consideration of related donors in such cases.