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Annals of Oncology Advance Access originally published online on February 16, 2007
Annals of Oncology 2007 18(4):679-688; doi:10.1093/annonc/mdl496
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© 2007 European Society for Medical Oncology

hematologic malignancies

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

AM Evens1, JK Altman1, BB Mittal2, N Hou3, A Rademaker3, D Patton1, L Kaminer1, S Williams1, S Duffey1, D Variakojis4, S Singhal1, MS Tallman1, J Mehta1, JN Winter1 and LI Gordon1,*

1 Division of Hematology/Oncology, Hematopoietic Stem Cell Transplant Program and Lymphoma Program, Feinberg School of Medicine, Northwestern University and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
2 Department of Radiation Oncology
3 Department of Preventive Medicine
4 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

* Correspondence to: Dr L. I. Gordon, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, 676 North St Clair, Suite 850, Chicago, IL 60611, USA. Tel: +1-312-695-4517, Fax: +1-312-695-6189, E-mail: l-gordon{at}northwestern.edu.

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/m2) 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.

Key words: autologous transplantation, Hodgkin's lymphoma, outcomes, prognosis, therapy, total lymphoid irradiation

Received for publication September 26, 2006. Revision received November 21, 2006. Accepted for publication December 12, 2006.


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