Chaudhury Sonali, Sparapani Rodney, Hu Zhen-Huan, Nishihori Taiga, Abdel-Azim Hisham, Malone Adriana, Olsson Richard, Hamadani Mehdi, Daly Andrew, Bacher Ulrike, Wirk Baldeep M, Kamble Rammurti T, Gale Robert P, Wood William A, Hale Gregory, Wiernik Peter H, Hashmi Shahrukh K, Marks David, Ustun Celalettin, Munker Reinhold, Savani Bipin N, Alyea Edwin, Popat Uday, Sobecks Ronald, Kalaycio Matt, Maziarz Richard, Hijiya Nobuko, Saber Wael
Department of Pediatrics-Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2016 Jun;22(6):1056-1064. doi: 10.1016/j.bbmt.2016.02.015. Epub 2016 Mar 8.
Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age < 18 years, n = 177) and young adults (age 18 to 29 years, n = 272) with the goal of identifying prognostic factors. Post-HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in <18-year and 74% and 60% in 18- to 29-year group, respectively, by univariate analysis (P = .1 and = .6). Five-year rates of OS for HLA matched sibling donor (MSD) and bone marrow (BM) stem cell source were 83% and 80%, respectively. In multivariate analysis there was no effect of age (<18 versus 18 to 29) or pre-HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P < .001) and recent HCT (2003 to 2010; P = .04). LFS was superior with MSD (P < .001), BM as graft source (P = .001), and performance scores > 90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD.
儿童和年轻成人的慢性髓性白血病（CML）并不常见。年轻患者通过造血细胞移植（HCT）有较长的预期寿命和较低的发病率。长期使用酪氨酸激酶抑制剂（TKI）可能会导致显著的发病率。此外，慢性期患者进行HCT的指征尚未确立。因此，我们回顾性评估了向国际骨髓移植登记处（CIBMTR）报告的449例早期疾病的CML患者接受清髓性HCT的结果。我们分析了影响结果的各种因素，特别是年龄和HCT前TKI对儿科患者（年龄<18岁，n = 177）和年轻成人（年龄18至29岁，n = 272）的影响，目的是确定预后因素。HCT后5年总生存率（OS）和无白血病生存率（LFS）分别为75%和59%。单因素分析显示，<18岁组的OS和LFS率分别为76%和57%，18至29岁组分别为74%和60%（P = 0.1和P = 0.6）。HLA匹配同胞供体（MSD）和骨髓（BM）干细胞来源的5年OS率分别为83%和80%。多因素分析显示，年龄（<18岁与18至29岁）或HCT前TKI治疗对OS、LFS、移植相关死亡率或复发均无影响。OS的有利因素为MSD（P < 0.001）和近期HCT（2003至2010年；P = 0.04）。与无关或不匹配的外周血干细胞供体以及性能评分较低的受者相比，MSD（P < 0.001）、BM作为移植物来源（P = 0.001）以及性能评分>90（P = 0.03）时LFS更佳。年龄较大与慢性移植物抗宿主病的发生率增加相关（P = 0.0002）。在当前时代，早期CML的年轻患者和儿童HCT结果相似，BM移植物和MSD可实现最佳结果。
