title: Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma.
abstract: The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5-69 years). The median number of prior chemotherapy regimens was 2 (range, 1-4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3-158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1-12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%-61%), 47% (95% CI: 40%-53%), and 47% (95% CI: 40%-54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%-81%) as compared to 30% (95% CI: 16%-45%) for induction failure and 34% (95% CI: 26%-42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.
authors.affiliation: Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA. anademanee@coh.org
authors.forename: A
authors.initials: A
authors.lastname: Nademanee
authors.forename: A
authors.initials: A
authors.lastname: Molina
authors.forename: A
authors.initials: A
authors.lastname: Dagis
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: M R
authors.initials: MR
authors.lastname: O'Donnell
authors.forename: P
authors.initials: P
authors.lastname: Parker
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: I
authors.initials: I
authors.lastname: Planas
authors.forename: A
authors.initials: A
authors.lastname: Kashyap
authors.forename: R
authors.initials: R
authors.lastname: Spielberger
authors.forename: H
authors.initials: H
authors.lastname: Fung
authors.forename: A
authors.initials: A
authors.lastname: Krishnan
authors.forename: R
authors.initials: R
authors.lastname: Bhatia
authors.forename: K K
authors.initials: KK
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: K
authors.initials: K
authors.lastname: Margolin
authors.forename: W
authors.initials: W
authors.lastname: Chow
authors.forename: I
authors.initials: I
authors.lastname: Sniecinski
authors.forename: N
authors.initials: N
authors.lastname: Vora
authors.forename: M
authors.initials: M
authors.lastname: Slovak
authors.forename: J C
authors.initials: JC
authors.lastname: Niland
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation