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


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.
Evens
A M
AM
Division of Hematology/Oncology, Hematopoietic Stem Cell Transplant Program and Lymphoma Program, Feinberg School of Medicine, Northwestern University, 676 North St. Clair, Chicago, IL 60611, USA.
Altman
J K
JK
Mittal
B B
BB
Hou
N
N
Rademaker
A
A
Patton
D
D
Kaminer
L
L
Williams
S
S
Duffey
S
S
Variakojis
D
D
Singhal
S
S
Tallman
M S
MS
Mehta
J
J
Winter
J N
JN
Gordon
L I
LI
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D014182:Transplantation, Autologous