485 The association between juvenile xanthogranulomas in neurofibromatosis type 1 patients and the development of leukemia: A systematic review

Abstract

Importance: A subset of patients with neurofibromatosis type 1 (NF1) develop juvenile xanthogranulomas (JXGs), a non-Langerhans cell histiocytosis, and some of these patients also develop juvenile myelomonocytic leukemia (JMML). Yet, these associations are poorly delineated. Objective: Our objectives in this systematic review was to: (1) clarify the relationship between NF1, JXGs and JMML and identify patients that may benefit from additional screening, (2) describe the clinical characteristics of JXGs arising in NF1. Evidence Review: A literature search was performed within the PubMed database on July 7th, 2021. Articles were included if they were peer-reviewed human studies, in English, and discussed any association between NF1, JXG, and/or leukemia with individual patient data. Findings: Sixty-five articles met eligibility criteria, which included 181 individual patients. Fifty-six patients had NF1 and JXG without leukemia (Group 1), 98 patients had NF1 and leukemia (Group 2), 18 patients had NF1, JXG, and leukemia (Group3), and 9 patients had JXG and leukemia (Group 4). Among the 78 patients with NF1 and JXG, 23% (18/78) developed leukemia, and more specifically, 19% (15/78) developed JMML, which is higher than what has been reported in NF1 patients alone. Majority of patients with the triple association were male (93%, 14/15) and had a family history of NF1 (67%, 8/12). Conclusions: Our findings suggest that the NF1 patients with JXGs have an increased risk of developing JMML and leukemia, especially in males with a family history of NF1. Although the triple association remains rare, closer surveillance and screening of male patients with familial NF1 and JXGs lesions may be reasonable, particularly at early ages.