Chao N J, Kastrissios H, Long G D, Negrin R S, Horning S J, Wong R M, Blaschke T F, Blume K G
Bone Marrow Transplantation Program, Stanford University, California.
Cancer. 1995 Mar 15;75(6):1354-9. doi: 10.1002/1097-0142(19950315)75:6<1354::aid-cncr2820750618>3.0.co;2-m.
This trial studied the feasibility and efficacy of a new preparatory regimen for autologous bone marrow transplantation for patients with advanced lymphoid malignancies.
Twenty-one patients with Hodgkin's disease (n = 12) and non-Hodgkin's lymphoma (n = 9) were treated in this study. Lomustine was substituted for carmustine) in a dose-escalation study with an initial dose of 6 mg/kg and increasing by 3 mg/kg in groups of four patients. The preparatory regimen consisted of lomustine (6-15 mg/kg) orally on Day -6, etoposide (60 mg/kg) intravenously (i.v.) on Day -4, and cyclophosphamide (100 mg/kg) i.v. on Day -2. Peripheral blood progenitor cells and/or bone marrow were infused on Day 0.
Lomustine was well tolerated in all patients with no significant toxicity specific to this drug. Engraftment was prompt: the time to achieving greater than or equal to 500 granulocytes/microliters was 12 days (range, 9-16 days) and the time to achieving greater than or equal to 25,000 platelets/microliters without transfusion support was 16 days (range, 9-22 days). Five patients experienced interstitial pneumonitis, three of whom had active or recent interstitial pneumonitis before bone marrow transplantation, and one who just completed mantle irradiation. Three patients died from this preparatory regimen, one of progressive interstitial pneumonitis, one of Legionella pneumonia, and one of multiorgan failure. Three patients with non-Hodgkin's lymphoma relapsed. Fourteen patients are currently alive and disease free to date. The actuarial are currently alive and disease free to date. The actuarial disease free survival was 57%, with a median follow-up of 23 months (range, 1-48 months).
The preparatory regimen consisting of lomustine/etoposide/cyclophosphamide is active in treating patients with lymphomas. Further trials with high doses of lomustine are warranted.
本试验研究了一种用于晚期淋巴系统恶性肿瘤患者自体骨髓移植的新预处理方案的可行性和疗效。
本研究治疗了21例霍奇金病患者(n = 12)和非霍奇金淋巴瘤患者(n = 9)。在剂量递增研究中,用洛莫司汀替代卡莫司汀,初始剂量为6mg/kg,每4例患者一组,剂量递增3mg/kg。预处理方案包括在第-6天口服洛莫司汀(6 - 15mg/kg),在第-4天静脉注射依托泊苷(60mg/kg),在第-2天静脉注射环磷酰胺(100mg/kg)。在第0天输注外周血祖细胞和/或骨髓。
所有患者对洛莫司汀耐受性良好,无该药物特有的明显毒性。造血恢复迅速:达到≥500个粒细胞/微升的时间为12天(范围9 - 16天),在无输血支持的情况下达到≥25,000个血小板/微升的时间为16天(范围9 - 22天)。5例患者发生间质性肺炎,其中3例在骨髓移植前患有活动性或近期间质性肺炎,1例刚完成斗篷野照射。3例患者死于该预处理方案,1例死于进行性间质性肺炎,1例死于军团菌肺炎,1例死于多器官功能衰竭。3例非霍奇金淋巴瘤患者复发。14例患者目前存活且无疾病。精算无病生存率为57%,中位随访23个月(范围1 - 48个月)。
由洛莫司汀/依托泊苷/环磷酰胺组成的预处理方案在治疗淋巴瘤患者中有效。有必要进一步进行高剂量洛莫司汀的试验。