Czogala Malgorzata, Pawinska-Wasikowska Katarzyna, Ksiazek Teofila, Sikorska-Fic Barbara, Matysiak Michal, Skalska-Sadowska Jolanta, Wachowiak Jacek, Rodziewicz-Konarska Anna, Chybicka Alicja, Myszynska-Roslan Katarzyna, Krawczuk-Rybak Maryna, Grabowski Dominik, Kowalczyk Jerzy, Maciejka-Kemblowska Lucyna, Adamkiewicz-Drozynska Elzbieta, Bobeff Katarzyna, Mlynarski Wojciech, Tomaszewska Renata, Szczepanski Tomasz, Pohorecka Joanna, Chodala-Grzywacz Agnieszka, Karolczyk Grazyna, Mizia-Malarz Agnieszka, Mycko Katarzyna, Badowska Wanda, Zielezinska Karolina, Urasinski Tomasz, Nykiel Magdalena, Woszczyk Mariola, Ciebiera Malgorzata, Chaber Radosław, Skoczen Szymon, Balwierz Walentyna
Department of Pediatric Oncology and Hematology, Institute of Pediatrics, Jagiellonian University Medical College, Kraków, Poland.
Department of Pediatric Oncology and Hematology, University Children Hospital, Kraków, Poland.
Front Pediatr. 2020 Jun 19;8:277. doi: 10.3389/fped.2020.00277. eCollection 2020.
Children with Down syndrome (DS) have increased risk of myeloid leukemia (ML), but specific treatment protocols ensure excellent outcome. This study was a retrospective analysis of the treatment results and genetic characteristics of ML of DS (ML-DS) in Poland from 2005 to 2019. All 54 patients with ML-DS registered in the Polish Pediatric Leukemia and Lymphoma Study Group in analyzed period were enrolled to the study. There were 34 children treated with Acute Myeloid Leukemia-Berlin-Frankfurt-Munster 2004 Interim Protocol (group I) and 20 patients treated with ML-DS 2006 Protocol (group II). In the first protocol, there was reduction of the antracyclines doses and intrathecal treatment for ML-DS compared to non-DS patients. In the second protocol, further reduction of the treatment was introduced (omission of etoposide in the last cycle, no maintenance therapy). Probabilities of 5-year overall survival (OS), event-free survival (EFS), and relapse-free survival in the whole analyzed group were 0.85 ± 0.05, 0.83 ± 0.05, and 0.97 ± 0.03, respectively. No significant differences were found between two protocols in the terms of OS and EFS (0.79 ± 0.07 vs. 0.95 ± 0.05, = 0.14, and 0.76 ± 0.07 vs. 0.95 ± 0.05, = 0.12, respectively). All deaths were caused by the treatment-related toxicities. Reduction of the treatment-related mortality was noticed (20% in group I and 5% in group II). The only one relapse in the whole cohort occurred in the patient from group I, older than 4 years, without gene mutation. He was treated successfully with IdaFLA cycle followed by hematopoietic stem cell transplantation from matched sibling donor. No significant prognostic factor was found in the study group probably due to low number of patients in the subgroups. The study confirms that the reduced intensity protocols are very effective in ML-DS patients. The only cause of deaths was toxicities; however, systematic decrease of the treatment-related mortality was noticed.
唐氏综合征（DS）患儿患髓系白血病（ML）的风险增加，但特定的治疗方案可确保良好的治疗效果。本研究对2005年至2019年波兰DS相关ML（ML-DS）的治疗结果和基因特征进行了回顾性分析。分析期间在波兰儿科白血病和淋巴瘤研究组登记的所有54例ML-DS患者均纳入本研究。34例儿童采用2004年急性髓系白血病-柏林-法兰克福-明斯特临时方案治疗（第一组），20例患者采用2006年ML-DS方案治疗（第二组）。在第一个方案中，与非DS患者相比，ML-DS的蒽环类药物剂量和鞘内治疗有所减少。在第二个方案中，进一步减少了治疗（最后一个周期省略依托泊苷，无维持治疗）。整个分析组的5年总生存率（OS）、无事件生存率（EFS）和无复发生存率分别为0.85±0.05,0.83±0.05和0.97±0.03。在OS和EFS方面，两个方案之间未发现显著差异（分别为0.79±0.07对0.95±0.05，P=0.14，以及0.76±0.07对0.95±0.05，P=0.12）。所有死亡均由治疗相关毒性引起。注意到治疗相关死亡率有所降低（第一组为20%，第二组为5%）。整个队列中唯一的一例复发发生在第一组中一名年龄大于4岁、无基因突变的患者身上。他成功接受了IdaFLA周期治疗，随后接受了来自匹配同胞供体的造血干细胞移植。由于亚组中患者数量较少，研究组未发现显著的预后因素。该研究证实，降低强度的方案对ML-DS患者非常有效。死亡的唯一原因是毒性；然而，注意到治疗相关死亡率有系统性下降。
