Winter Stuart S, Holdsworth Mark T, Devidas Meenakshi, Raisch Dennis W, Chauvenet Allen, Ravindranath Yaddanapudi, Ducore Jonathan M, Amylon Michael D
Department of Pediatrics, Albuquerque, New Mexico 87131, USA.
Pediatr Blood Cancer. 2006 Feb;46(2):179-86. doi: 10.1002/pbc.20429.
A previous Pediatric Oncology Group (POG) study showed high incidence of secondary acute myelogenous leukemia (AML) in children treated for T-cell acute lymphoblastic leukemia (T-ALL) or higher-stage lymphoblastic lymphoma. To prevent secondary neoplasms, induce prolonged asparagine depletion, and maintain high event-free survival (EFS) in children with newly diagnosed T-ALL or higher-stage non-Hodgkins lymphoma (NHL), we designed this pilot study to determine feasibility and safety of substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase.
Forty-five patients were entered, 29 with T-ALL and 16 with higher-stage NHL. Forty-two of 45 patients achieved complete remission (CR), and 27 completed the therapy in continuous CR. Treatment consisted of 4-week induction then 6 weeks consolidation and ten 9-week maintenance cycles. Therapy primarily comprised antimetabolites, anthracyclines, alkylating agents, and asparaginase. Expected chemotherapy duration was 100 weeks.
Forty-two of 45 patients achieved CR, and 27 completed therapy. The most common toxicities were Grade 3 or 4 myelosuppression after cyclophosphamide/cytarabine and allergic reactions to asparaginase. Two died of sepsis early in maintenance. Five-year EFS was 68.5% (SE 9.1%) for T-ALL and 81.3% (SE 9.8%) for NHL. Five-year EFS was 73.1% (SE 6.8%) for the entire cohort. No patients treated entirely on this study developed secondary neoplasms. One patient taken off study for asparaginase toxicity was treated with multiagent therapy that contained teniposide, and died from secondary myelodysplasia (sMDS)/AML.
Substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase in a dose-intensive regimen was feasible in children and young adults with newly diagnosed T-ALL or higher-stage NHL. EFS was not compromised and secondary neoplasms were decreased.
先前一项儿科肿瘤学组（POG）的研究显示，接受T细胞急性淋巴细胞白血病（T-ALL）或更高分期淋巴细胞淋巴瘤治疗的儿童中，继发性急性髓系白血病（AML）的发病率很高。为预防继发性肿瘤、诱导天冬酰胺长期耗竭并维持新诊断的T-ALL或更高分期非霍奇金淋巴瘤（NHL）患儿的高无事件生存率（EFS），我们设计了这项初步研究，以确定用甲氨蝶呤/巯嘌呤替代替尼泊苷/阿糖胞苷以及用聚乙二醇化天冬酰胺酶替代天然天冬酰胺酶的可行性和安全性。
入组45例患者，其中29例为T-ALL，16例为更高分期的NHL。45例患者中有42例实现完全缓解（CR），27例在持续CR状态下完成治疗。治疗包括4周诱导期，随后6周巩固期和十个9周维持周期。治疗主要包括抗代谢药物、蒽环类药物、烷化剂和天冬酰胺酶。预计化疗持续时间为100周。
45例患者中有42例实现CR，27例完成治疗。最常见的毒性反应是环磷酰胺/阿糖胞苷后的3级或4级骨髓抑制以及对天冬酰胺酶的过敏反应。2例在维持期早期死于败血症。T-ALL的5年EFS为68.5%（标准误9.1%），NHL为81.3%（标准误9.8%）。整个队列的5年EFS为73.1%（标准误6.8%）。在本研究中接受全部治疗的患者均未发生继发性肿瘤。1例因天冬酰胺酶毒性退出研究的患者接受了含替尼泊苷的多药治疗，并死于继发性骨髓发育异常（sMDS）/AML。
在新诊断的T-ALL或更高分期NHL的儿童和年轻成人中，在剂量密集方案中用甲氨蝶呤/巯嘌呤替代替尼泊苷/阿糖胞苷以及用聚乙二醇化天冬酰胺酶替代天然天冬酰胺酶是可行的。EFS未受影响，继发性肿瘤减少。
