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. 2021 Jan;41(1):51-58.
doi: 10.1007/s10875-020-00883-7. Epub 2020 Oct 4.

Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD)

Quentin Neven  1 , Cécile Boulanger  2 , Annelyse Bruwier  3 , Maëlle de Ville de Goyet  2 , Isabelle Meyts  4   5 , Leen Moens  4 , An Van Damme  2 , Bénédicte Brichard  2
Affiliations

Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD)

Quentin Neven et al. J Clin Immunol. 2021 Jan.

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.

Keywords: Autoimmunity; KRAS; NRAS; Ras-associated autoimmune leukoproliferative disorder; malignancy.

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