Neven Quentin, Boulanger Cécile, Bruwier Annelyse, de Ville de Goyet Maëlle, Meyts Isabelle, Moens Leen, Van Damme An, Brichard Bénédicte
Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Avenue Hippocrate 10, 1200, Brussels, Belgium.
Department of Pediatrics, Grand Hôpital de Charleroi, Charleroi, Belgium.
J Clin Immunol. 2021 Jan;41(1):51-58. doi: 10.1007/s10875-020-00883-7. Epub 2020 Oct 4.
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.
Ras相关的自身免疫性白细胞增殖性疾病（RALD）是一种临床实体，最初在因自身免疫性淋巴细胞增殖综合征（ALPS）样表型接受评估的患者中被发现。RALD究竟是一种慢性良性淋巴细胞增殖性疾病还是一种癌前病变，仍存在争议。我们报告了一例7岁女孩的病例，该女孩因体细胞KRAS突变被诊断为RALD，随后进展为青少年骨髓单核细胞白血病表型，最终演变为急性髓系白血病。该病例报告促使我们通过检索PubMed和Embase上发表的所有RALD病例进行文献综述。我们共识别出27例RALD患者。男女比例为1:1，发病时的中位年龄为2岁（范围3个月至36岁）。16例患者（59%）存在KRAS体细胞突变，11例患者（41%）存在NRAS体细胞突变。最常见的特征是脾肿大（26/27例患者）、自身免疫性血细胞减少（15/16例患者）、单核细胞增多（18/24例患者）、心包炎（6例患者）和皮肤受累（4例患者）。两名患者继而发展为血液系统恶性肿瘤。总之，当前病例记录了关于RALD长期恶性肿瘤风险的又一警示。
