Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin's disease and non-Hodgkin's lymphoma.
OBJECTIVE
High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies.


METHODS
Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow.


RESULTS
The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years.


CONCLUSIONS
The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.
Horning
S J
SJ
Department of Medicine, Stanford University Medical Center, Palo Alto, CA 94304-1808.
Negrin
R S
RS
Chao
J C
JC
Long
G D
GD
Hoppe
R T
RT
Blume
K G
KG
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012008:Recurrence; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
D005047:Etoposide; D003520:Cyclophosphamide