Autologous Stem-Cell Transplantation for Poor-Risk and Relapsed Intermediate- and High-Grade Non-Hodgkin's Lymphoma

Auayporn Nademanee, Arturo Molina, Andrew Dagis, David S. Snyder, Margaret R. O'Donnell, Pablo Parker, Anthony Stein, Eileen Smith, Ina Planas, Ashwin Kashyap, Ricardo Spielberger, Henry Fung, Amrita Krishnan, Ravi Bhatia, K. K. Wong, George Somlo, Kim Margolin, Warren Chow, Irene Sniecinski, Nayana VoraMarilyn Slovak, Joyce C. Niland, Stephen J. Forman

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47 Scopus citations

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 [Cl]: 49%-61%), 47% (95% Cl: 40%-53%), and 47% (95% Cl: 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% Cl: 62%-81%) as compared to 30% (95% Cl: 16%-45%) for induction failure and 34% (95% Cl: 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.

Original languageEnglish
Pages (from-to)46-54
Number of pages9
JournalClinical Lymphoma
Volume1
Issue number1
DOIs
StatePublished - Jun 2000

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Bone Marrow Transplantation
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Lymphoma, Non-Hodgkin/mortality
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Transplantation, Autologous
  • Whole-Body Irradiation

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