Chopra R, McMillan A K, Linch D C, Yuklea S, Taghipour G, Pearce R, Patterson K G, Goldstone A H
Department of Haematology, University College and Middlesex School of Medicine, London, UK.
Blood. 1993 Mar 1;81(5):1137-45.
Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarial overall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses > 10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.
尽管大剂量化疗和自体骨髓移植(ABMT)越来越多地用于复发性和难治性霍奇金病的治疗,但很少有大型单中心研究报道有足够的随访时间来全面评估这种治疗方式。我们报告了155例高危霍奇金病患者,他们接受了大剂量BEAM(卡氮芥、依托泊苷、阿糖胞苷和美法仑)化疗及ABMT,并进行了为期8年的研究。所有患者在接受氮芥、长春新碱、丙卡巴肼、泼尼松类治疗时均未达到缓解,且初诊时预后不良,或在初始交替方案治疗1年内未达到完全缓解或复发,或经过两种或更多线治疗仍未缓解。在进行ABMT时,患者的复发状态如下:46例患者对诱导治疗原发难治,7例为良好部分缓解者,52例处于首次复发,37例处于第二次复发,13例处于第三次复发。78例患者患有化疗耐药性疾病,33例在进行ABMT时患有化疗敏感性疾病,44例在最近一次复发时未进行化疗敏感性检测。ABMT后前90天的总体手术相关死亡率为10%。3个月时,43例患者(28%)被评估为完全缓解者,72例患者部分缓解(46%),24例患者(16%)无缓解或疾病进展。然而,到6个月时,53例(24%)患者被评估为完全缓解者,51例(33%)患者疾病无进展。45例患者在ABMT后接受了放疗,用于残留肿块(41例患者)或既往大块病灶部位(4例患者)。5年时的精算总生存率和无进展生存率分别为55%和50%。多因素分析显示,有大块病灶(肿块>10 cm)、预处理严重(接受三线或更多线治疗)的患者以及女性患者的预后明显较差。复发状态对无进展生存也有显著影响,处于第二次复发(60%)和第三次复发(70%)的患者比首次复发(44%)或原发难治性疾病(33%)的患者预后更好。对先前化疗的反应不能预测无进展生存。这些结果使得能够对大剂量化疗联合ABMT与传统剂量挽救治疗进行比较。此外,尽管总体结果非常令人鼓舞,但某些群体的预后不佳。