Phase I/II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin's lymphoma.

Abstract

BACKGROUND:

The standard approach to treatment of relapsed/refractory Hodgkin's lymphoma (HL) is high-dose chemotherapy conditioning followed by autologous hematopoietic stem-cell transplantation (aHSCT). We report the results of a prospective phase I/II clinical trial of accelerated hyperfractionated total lymphoid irradiation (TLI) immediately followed by high-dose chemotherapy for relapsed/refractory HL.

PATIENTS AND METHODS:

Forty-eight patients underwent aHSCT with either sequential TLI/chemotherapy (n = 32) or chemotherapy-alone conditioning (n = 16), based on prior radiation exposure. The first 22 patients enrolled on trial received escalating doses of etoposide (1600-2100 mg/m(2)) with high-dose carboplatin and cyclophosphamide.

RESULTS:

No dose-limiting toxicity was seen and TLI/chemotherapy was well tolerated. The 5-year event-free survival (EFS) estimate for all patients was 44% with overall survival (OS) of 48%. Five-year EFS and OS for the TLI/chemotherapy group was 63% and 61%, respectively, compared with 6% and 27%, respectively, for the chemotherapy-alone group (P < 0.0001 and P = 0.04, respectively). Patients with primary induction failure HL who received TLI/chemotherapy had 5-year EFS and OS rate of 83%. The 100-day treatment-related mortality was 4.2% and two secondary cancers were seen. Significant factors predicting survival by multivariate analysis included TLI/chemotherapy conditioning and B symptoms at relapse.

CONCLUSIONS:

Sequential TLI/chemotherapy conditioning for relapsed/refractory HL is safe and associated with excellent long-term survival rates.

• Authors: A M Evens, J K Altman, B B Mittal, N Hou, A Rademaker, D Patton, L Kaminer, S Williams, S Duffey, D Variakojis, S Singhal, M S Tallman, J Mehta, J N Winter, L I Gordon
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 18 Issue 4 Pg. 679-88 (Apr 2007) ISSN: 0923-7534 [Print] England
• PMID: 17307757 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Combined Modality Therapy
• Female
• Hematopoietic Stem Cell Transplantation
• Hodgkin Disease (mortality, therapy)
• Humans
• Lymphatic Irradiation
• Male
• Middle Aged
• Prognosis
• Prospective Studies
• Recurrence
• Transplantation, Autologous