Pediatric secondary Chronic myelogenous leukemia in a patient with Hemophagocytic lymphohistiocytosis carrying UNC13D,LYST and ITK variantChengshuang Huang1, 2, 3 Pei Huang1, 3 Xi Luo1, 3 Zhixu He1, 3 Yan Chen1, 31Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine, Zunyi Medical University, Zunyi, 563000, China2Department of Emergency Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China3Department of Pediatrics, Guizhou Children’s Hospital, Zunyi, 563000, ChinaAddress correspondence to: Yan Chen, MD, The Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, 563000, China, cyz600@163.com, +86-0851-28608293Short title: Pediatric secondary CML in a patient with HLHKeywords: Hemophagocytic lymphohistiocytosis; Secondary CML; Chemotherapy; Genetic screeningText: 839 wordsNumber of Tables: 1

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease. This case report describes a secondary chronic myelogenous leukemia (CML) in a nine-year-old male after treatment with a combination of etoposide (VP16), steroids and cyclosporin for HLH. VP16 can potentially induce leukemia, and single nucleotide polymorphisms may be involved in the pathogenesis of CML. We speculate that genetic backgrounds combined with chemotherapeutic drugs lead to secondary CML. This case report alerts physicians to the importance of genetic screening and the rare side effects of VP16 in children with HLH.