Schmidt Franziska, Erlacher Miriam, Niemeyer Charlotte, Reinhardt Dirk, Klusmann Jan-Henning
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Front Pediatr. 2022 Nov 9;10:1046586. doi: 10.3389/fped.2022.1046586. eCollection 2022.
Twelve to 22% of pediatric acute myeloid leukemia (AML) patients present with hyperleukocytosis, which is one of the main risk factors of early death due to its clinical complications: leukostasis, causing pulmonary or central nervous system injuries, tumor lysis syndrome, and disseminated intravascular coagulation. Sorafenib is a multi-kinase inhibitor that blocks the Fms-Related Tyrosine Kinase 3 receptor () in AML patients with a -internal tandem duplication (-ITD), leading to a reduction of proliferation. Here we report four diagnosed or relapsed pediatric -ITD-positive AML patients with hyperleukocytosis, which were treated with sorafenib in combination with cytoreductive chemotherapy prior to the start of the induction phase. We observed a fast reduction of white blood cells in peripheral blood and bone marrow. This resulted in a rapid clinical stabilization of the patients. Adverse side effects-such as dermatologic toxicity, elevation of transaminases and hypertension-occurred but were mild and inductive chemotherapy could be started in parallel or subsequently. This implies sorafenib as a safe and effective treatment option in combination with chemotherapy during cytoreductive prephase for children with this life-threatening condition.
12%至22%的儿童急性髓系白血病（AML）患者存在白细胞增多症，这是导致早期死亡的主要危险因素之一，因为其临床并发症包括：白细胞淤滞，可导致肺部或中枢神经系统损伤、肿瘤溶解综合征和弥散性血管内凝血。索拉非尼是一种多激酶抑制剂，可阻断伴有α-内部串联重复（α-ITD）的AML患者的Fms相关酪氨酸激酶3受体（），从而导致增殖减少。在此，我们报告了4例诊断或复发的伴有白细胞增多症的儿童α-ITD阳性AML患者，在诱导期开始前，他们接受了索拉非尼联合减瘤化疗的治疗。我们观察到外周血和骨髓中的白细胞迅速减少。这使得患者的临床状况迅速稳定。出现了如皮肤毒性、转氨酶升高和高血压等不良副作用，但症状较轻，诱导化疗可同时或随后开始。这意味着索拉非尼作为一种安全有效的治疗选择，可在减瘤前期与化疗联合用于患有这种危及生命疾病的儿童。
