Boulad F, Steinherz P, Reyes B, Heller G, Gillio A P, Small T N, Brochstein J A, Kernan N A, O'Reilly R J
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1999 Jan;17(1):197-207. doi: 10.1200/JCO.1999.17.1.197.
A retrospective analysis of the treatment of childhood acute lymphoblastic leukemia (ALL) in second remission (CR2) was undertaken at our institution to compare the outcome and prognostic factors of patients treated with chemotherapy or allogeneic bone marrow transplantation (BMT).
Seventy-five children who suffered a medullary relapse and achieved a second remission were treated with either an unmodified allogeneic HLA-matched sibling BMT after hyperfractionated total body irradiation (TBI) and cyclophosphamide (n = 38) or chemotherapy according to institutional chemotherapy protocols (n = 37). To avoid the bias of survival from the attainment of second remission in favor of BMT, the final comparative statistical analysis used the landmark approach and comprised 37 and 29 patients from the BMT and chemotherapy groups, respectively
The disease-free survival (DFS) rate was 62% and 26% at 5 years, respectively, for the BMT and the chemotherapy groups (P = .03), with relapse rates of 19% and 67%, respectively, for these two groups (P = .01). There was an overall advantage for the BMT therapeutic approach, as compared with chemotherapy, for patients with ALL in CR2 (1) for patients with a WBC count (at diagnosis) of 20 x 10(9)/L or higher (DFS, 40% v 0%) and those with a WBC count of less than 20 x 10(9)/L (DFS, 73% v35%), (2) for patients whose duration of CR1 was less than 24 months (DFS 48% v 9%) and for patients whose duration of CR1 was 24 months or longer (DFS, 81% v 37%) and (3) for patients who were initially treated with intensive regimens incorporating more than five chemotherapy agents (DFS, 57% v 20%) and for patients treated with five agents or fewer (DFS, 72% v 32%).
In our single-institution series, unmodified HLA-matched allogeneic sibling transplants using hyperfractionated TBI and cyclophosphamide for patients with ALL in CR2 have resulted in superior outcome with a significantly improved probability of DFS and a lower relapse rate, as compared with those for patients treated with chemotherapy, regardless of the duration of first remission, the disease characteristics at diagnosis, or the intensity of prior treatment during first remission.
我们机构对儿童急性淋巴细胞白血病(ALL)第二次缓解期(CR2)的治疗进行了回顾性分析,以比较接受化疗或异基因骨髓移植(BMT)治疗的患者的结局和预后因素。
75例发生髓系复发并获得第二次缓解的儿童,其中38例在超分割全身照射(TBI)和环磷酰胺治疗后接受了未修饰的 HLA 匹配同胞异基因 BMT,37例根据机构化疗方案接受化疗。为避免因达到第二次缓解而有利于 BMT 的生存偏倚,最终的比较统计分析采用了标志性方法,BMT组和化疗组分别纳入37例和29例患者。
BMT组和化疗组5年无病生存率(DFS)分别为62%和26%(P = 0.03),两组复发率分别为19%和67%(P = 0.01)。与化疗相比,对于CR2期的ALL患者,BMT治疗方法总体上具有优势:(1)诊断时白细胞计数(WBC)≥20×10⁹/L的患者(DFS,40%对0%)和WBC<20×10⁹/L的患者(DFS,73%对35%);(2)CR1期持续时间<24个月的患者(DFS,48%对9%)和CR1期持续时间≥24个月的患者(DFS,81%对37%);(3)最初接受包含五种以上化疗药物的强化方案治疗的患者(DFS,57%对20%)和接受五种或更少药物治疗的患者(DFS,72%对32%)。
在我们单机构的系列研究中,对于CR2期的ALL患者,采用超分割TBI和环磷酰胺的未修饰HLA匹配同胞异基因移植,与化疗患者相比,结局更优,DFS概率显著提高,复发率更低,无论首次缓解期的持续时间、诊断时的疾病特征或首次缓解期的前期治疗强度如何。