1. Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD)
- Author
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Leen Moens, Cécile Boulanger, Isabelle Meyts, Bénédicte Brichard, An Van Damme, Maëlle de Ville de Goyet, Annelyse Bruwier, Quentin Neven, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique
- Subjects
0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Male ,Ras-associated autoimmune leukoproliferative disorder ,Autoimmunity ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Immunology and Allergy ,Child ,Skin ,Juvenile myelomonocytic leukemia ,RAS-associated autoimmune leukoproliferative disorder ,Disease Management ,Prognosis ,Combined Modality Therapy ,Phenotype ,Treatment Outcome ,Child, Preschool ,Female ,KRAS ,Disease Susceptibility ,Adult ,medicine.medical_specialty ,Adolescent ,Genotype ,Immunology ,Karyotype ,NRAS ,Malignancy ,Autoimmune Diseases ,Diagnosis, Differential ,03 medical and health sciences ,Young Adult ,Monocytosis ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Alleles ,Myeloproliferative Disorders ,business.industry ,Autoimmune Cytopenia ,Autoimmune Lymphoproliferative Syndrome ,Infant ,medicine.disease ,030104 developmental biology ,Autoimmune lymphoproliferative syndrome ,Mutation ,ras Proteins ,business ,030215 immunology - Abstract
Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. It remains a matter of debate whether RALD is a chronic and benign lymphoproliferative disorder or a pre-malignant condition. We report the case of a 7-year-old girl diagnosed with RALD due to somatic KRAS mutation who progressed to a juvenile myelomonocytic leukemia phenotype and finally evolved into acute myeloid leukemia. The case report prompted a literature review by a search for all RALD cases published in PubMed and Embase. We identified 27 patients with RALD. The male-to-female ratio was 1:1 and median age at disease onset was 2 years (range 3 months-36 years). Sixteen patients (59%) harbored somatic mutations in KRAS and 11 patients (41%) somatic mutations in NRAS. The most common features were splenomegaly (26/27 patients), autoimmune cytopenia (15/16 patients), monocytosis (18/24 patients), pericarditis (6 patients), and skin involvement (4 patients). Two patients went on to develop a hematopoietic malignancy. In summary, the current case documents an additional warning about the long-term risk of malignancy in RALD.
- Published
- 2020