title: High-dose carmustine, etoposide, and cisplatin for autologous stem cell transplantation with or without involved-field radiation for relapsed/refractory lymphoma: an effective regimen with low morbidity and mortality.
abstract: Over a 10-year period (January 1993 to October 2002), 101 relapsed or refractory non-Hodgkin lymphoma patients were treated at our center with high-dose chemotherapy and autologous transplantation. The median patient age was 54 years (range, 25-70 years). Thirty-two patients had indolent (low-grade), 42 had aggressive (intermediate-grade), and 27 had very aggressive (high-grade) non-Hodgkin lymphoma. Thirty-six patients had primary refractory disease, 20 had a chemoresistant relapse, 35 patients had a chemosensitive relapse, and 10 patients were "initial high risk" patients. The median number of prior chemotherapy regimens was 2 (range, 1-5). The preparative regimen (BEP) was bischloroethylnitrosourea (BCNU) 600 mg/m 2 , etoposide 2400 mg/m 2 , and Platinol (cisplatin) 200 mg/m 2 given intravenously over 5 days. Within 3 weeks before transplantation, 70 patients received involved-field radiotherapy (IFR) 20 Gy to sites of currently active (>2 cm) or prior bulky (>5 cm) disease. Most patients (n = 93) received mobilized peripheral blood stem cells (median CD34 + cell dose, 6.7 x 10 6 /kg). Median neutrophil (>500/microL) and platelet (>20 000/microL, untransfused) recoveries were 11 days (range, 7-19 days) and 14 days (range, 7-36 days), respectively. At a median follow-up of 41 months (range, 4 to 118 months) for survivors, Kaplan-Meier 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 58.6% and 51.1%, respectively. Four patients (4%) died within 30 days of stem cell infusion (1 pulmonary embolism, 2 septicemias with multiorgan failure, and 1 progressive lymphoma). Two patients (2%) developed interstitial pneumonitis most likely secondary to high-dose BCNU. Three cases (3%) of secondary acute myelogenous leukemia occurred. On multivariate analysis, age (<60 or > or =60 years), histologic grade (low versus intermediate or high), the use of IFR, and chemotherapy response at baseline did not affect OS or DFS. Of 70 patients given IFR, 27 relapsed: 10 (37%) within and 17 (63%) outside the radiation field. The use of IFR did not affect either OS or DFS, probably because IFR was offered to patients with bulky or chemoresistant disease. BEP with or without IFR is a highly effective and well-tolerated regimen in the relapsed/refractory lymphoma setting. It has low morbidity and transplant-related mortality and a low incidence (3%) of posttransplantation malignancy.
authors.affiliation: Department of Medicine, Comprehensive Cancer Center of the University Hospitals of Cleveland/Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Punit D
authors.initials: PD
authors.lastname: Wadhwa
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Omer N
authors.initials: ON
authors.lastname: Koc
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Cooper
authors.forename: Robert M
authors.initials: RM
authors.lastname: Fox
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Creger
authors.forename: David L
authors.initials: DL
authors.lastname: Bajor
authors.forename: Teja
authors.initials: T
authors.lastname: Bedi
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Laughlin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Payne
authors.forename: Stanton L
authors.initials: SL
authors.lastname: Gerson
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods / Q000401:mortality; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D002945:Cisplatin; D002330:Carmustine