非霍奇金淋巴瘤的自体干细胞移植：移植物净化及移植后放疗的作用——对单一机构120例接受自体移植患者的回顾性分析结果

Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution.

作者信息

Fouillard L, Laporte J P, Labopin M, Lesage S, Isnard F, Douay L, Lopez M, Aoudjhane M, Zunic P, Cheron N, Stachowiak J, Lemonnier M P, Andreu G, Belkacemi Y, Noël-Walter M P, Morel P, Fenaux P, Jouet J P, Bauters F, Najman A, Gorin N C

机构信息

Service des Maladies du Sang, and Etablissement de transfusion Sanguine Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Paris, France.

出版信息

J Clin Oncol. 1998 Aug;16(8):2803-16. doi: 10.1200/JCO.1998.16.8.2803.

DOI:10.1200/JCO.1998.16.8.2803

PMID:9704733

Abstract

PURPOSE

To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution.

PATIENTS AND METHODS

A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement.

RESULTS

Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS.

CONCLUSION

This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.

摘要

目的

回顾性分析1979年至1995年在单一机构接受自体移植的非霍奇金淋巴瘤（NHL）患者的生存情况及预后因素。

患者与方法

共有120例患者接受自体移植，其中64例为侵袭性NHL，56例为低度恶性NHL。104例患者采用卡莫司汀（BCNU）、依托泊苷、阿糖胞苷和美法仑（BEAM）方案。101例患者的自体移植采用骨髓。63例患者的骨髓在体外经马磷酰胺净化（32例采用调整剂量[AD]，31例采用单一剂量[UD]）；27例患者接受了CD34+选择的移植物。强化治疗后，45例患者在先前受累部位接受了额外的放疗。

结果

低度恶性NHL患者在首次完全缓解（CR1）、首次部分缓解（PR1）以及第二次或更后的完全缓解（CR2）时接受移植，5年时的无事件生存率（EFS）分别为75%±12%、46%±18%和57%±24%，复发率（RI）分别为21%±12%、49%±19%和43%±25%，移植相关死亡率（TRM）分别为5%±5%、10%±7%和0%。侵袭性NHL患者在CR1、PR1、CR2或更后、耐药复发或原发性难治性疾病时接受移植，EFS分别为73%±9%、58%±19%、29%±16%和10%±9%，RI分别为22%±9%、14%±9%、77%±18%和66%±20%，TRM分别为6%±6%、32%±21%、11%±10%和71%±22%。在首次缓解时接受前期自体移植的患者中，单因素分析（P = 0.03）和多因素分析（P = 0.02，相对风险[RR] = 0.021）显示，额外放疗与更高的EFS相关。通过单因素分析评估了马磷酰胺净化移植物对结果的作用，该作用通过净化后每千克输注的集落形成单位-粒细胞-巨噬细胞（CFU-GM）剂量来反映：首次缓解时接受较低剂量CFU-GM的患者RI较低，EFS较高。