Ladenstein R, Pearce R, Hartmann O, Patte C, Goldstone T, Philip T
St. Anna Children's Hospital, Vienna, Austria.
Blood. 1997 Oct 15;90(8):2921-30.
To evaluate the role of high-dose chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT) in children with poor-prognosis Burkitt's lymphoma, the European Lymphoma BMT registry was critically reviewed. Between February 1979 and July 1991, a selected group of 89 children (78 boys and 11 girls) were considered as ABMT candidates in 12 European cancer centers for the following reasons: poor initial response (PIR) to first-line chemotherapy in 28 patients, primary refractory disease (PRD) in nine patients, sensitive relapse (SR) in 38 patients, and resistant relapse (RR) in 14 patients. The median age at ABMT was 8.2 years (range, 2.8 to 16.2 years). Thus, this report reflects data for patients surviving the salvage attempt deemed appropriate for HDC/ABMT and who then actually underwent the transplant procedure. The median follow-up period after HDC/ABMT was 4.3 years (range, 2 to 12 years). The prognosis was dismal for PRD patients and those with RR, ie, all patients died within 1 year. The 5-year event-free survival (EFS) was 56.6% (P < .0001) for patients in partial remission (PR) and 48.7% (P = .002) for patients with SR. The toxic death rate was 11.1%. Continuous complete remissions (CRs) in 39.4% of these otherwise incurable children highlight the fact that HDC/ABMT was an effective complementary procedure after conventional-dose chemotherapy protocols used during the given period. In addition, these data show that patients with PRD or RR clearly had no advantage from this aggressive and cost-intensive procedure. It has to be considered that the need for HDC/ABMT has greatly diminished in parallel with the improvement in survival using the modern intensive pulsed CCT of current protocols. To further rescue patients failing to respond to modern protocols, new approaches appear necessary, ie, combinations of HDC with antibody-targeted therapy plus allogeneic BMT for the additional benefits of the potential graft-versus-lymphoma effect.
为评估大剂量化疗(HDC)联合自体骨髓移植(ABMT)在预后不良的伯基特淋巴瘤患儿中的作用,对欧洲淋巴瘤骨髓移植登记处进行了严格审查。1979年2月至1991年7月期间,欧洲12个癌症中心选定的89名儿童(78名男孩和11名女孩)被视为ABMT候选者,原因如下:28例患者对一线化疗初始反应不佳(PIR),9例患者为原发性难治性疾病(PRD),38例患者为敏感复发(SR),14例患者为耐药复发(RR)。ABMT时的中位年龄为8.2岁(范围2.8至16.2岁)。因此,本报告反映了那些在被认为适合HDC/ABMT的挽救性治疗尝试中存活下来并实际接受移植手术的患者的数据。HDC/ABMT后的中位随访期为4.3年(范围2至12年)。PRD患者和RR患者的预后很差,即所有患者均在1年内死亡。部分缓解(PR)患者的5年无事件生存率(EFS)为56.6%(P <.0001),SR患者为48.7%(P =.002)。毒性死亡率为11.1%。在这些原本无法治愈的儿童中,39.4%持续完全缓解(CR),这突出表明HDC/ABMT是在给定时期内使用的传统剂量化疗方案后的一种有效补充治疗手段。此外,这些数据表明,PRD或RR患者显然无法从这种积极且成本高昂的治疗手段中获益。必须考虑到,随着当前方案中现代强化脉冲化疗在生存率方面的提高,对HDC/ABMT的需求已大幅减少。为了进一步挽救对现代方案无反应的患者,新的方法似乎是必要的,即HDC与抗体靶向治疗联合异基因骨髓移植,以获得潜在移植物抗淋巴瘤效应的额外益处。