Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma.
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.
Nademanee
A
A
Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA. anademanee@coh.org
Molina
A
A
Dagis
A
A
Snyder
D S
DS
O'Donnell
M R
MR
Parker
P
P
Stein
A
A
Smith
E
E
Planas
I
I
Kashyap
A
A
Spielberger
R
R
Fung
H
H
Krishnan
A
A
Bhatia
R
R
Wong
K K
KK
Somlo
G
G
Margolin
K
K
Chow
W
W
Sniecinski
I
I
Vora
N
N
Slovak
M
M
Niland
J C
JC
Forman
S J
SJ
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