Reece D E, Barnett M J, Connors J M, Fairey R N, Fay J W, Greer J P, Herzig G P, Herzig R H, Klingemann H G, LeMaistre C F
Leukemia/Bone Marrow Transplantation Program of British Columbia, British Columbia Cancer Agency, Vancouver General Hospital, Canada.
J Clin Oncol. 1991 Oct;9(10):1871-9. doi: 10.1200/JCO.1991.9.10.1871.
Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.
56例经进一步常规化疗被认为无法治愈的晚期霍奇金病患者进入一项方案，该方案包括大剂量环磷酰胺（7.2 g/m²）、卡莫司汀（BCNU；0.6 g/m²）和依托泊苷（VP16 - 213；2.4 g/m²）（CBV），随后进行自体骨髓移植（BMT）。所有患者先前的联合化疗均失败，除5例患者外，其余患者均接受过氮芥、长春新碱、丙卡巴肼和泼尼松（MOPP）以及多柔比星、博来霉素和长春碱（联合或不联合达卡巴嗪）（ABV[D]）治疗。34例符合条件的患者在接受CBV之前接受了短程常规化疗和/或累及野放疗。然而，在这些常规治疗后未进行正式的再分期；即这些治疗并非用于选择对移植有反应的患者，所有接受此类治疗的患者随后均接受了CBV和自体骨髓移植。44例患者（80%；95%置信区间[CI]，69%至91%）在接受CBV和BMT后达到完全缓解。方案入组时的体能状态以及在接受CBV之前使用常规细胞减灭疗法与缓解相关。中位随访时间目前为3.5年（范围，2.5至5.0年）。移植后5年的总生存率和无事件生存率的Kaplan - Meier估计值分别为53%（95% CI，37%至67%）和47%（95% CI，33%至60%）。在单因素分析中，方案入组时体能状态正常且无全身（“B”）症状的患者总生存率和无事件生存率有所提高。在多因素分析中，只有体能状态正常仍然具有显著性。17例患者出现疾病进展，精算发生率为39%（95% CI；26%至56%），除1例患者外，均发生在先前有活动性疾病的部位；我们的分析未确定疾病进展的预后因素。由中性粒细胞减少性败血症或间质性肺炎（IP）导致的毒性死亡发生在12例患者中（21%；95% CI，10%至32%）。CBV联合自体骨髓支持可使大量被认为用常规方法无法治愈的霍奇金病患者获得持久缓解。方案的改进甚至可能进一步提高BMT在这种恶性肿瘤中的治疗指数。
