High-dose chemo/radiotherapy and autologous bone marrow or stem cell transplantation for poor-risk advanced-stage Hodgkin's disease during first partial or complete remission.
Complete remission rates of 70-90% can be achieved following combination chemotherapy for patients with advanced-stage Hodgkin's disease (HD). Patients who present with unfavorable poor prognostic factors, however, have a 5-year disease-free survival of only 40-50%. In an attempt to improve the prognosis of 20 patients with poor-risk advanced-stage HD, we evaluated the role of early high-dose therapy (HDT) and autologous bone marrow/stem cell transplantation (ASCT) during the first complete or partial remission (CR/PR). Patients were eligible for ASCT if they either achieved a PR (defined as > 50% regression) (six patients), or achieved a CR (14 patients) but had presented with three or more of the following unfavorable features: stage IV disease with bone marrow involvement or > or = 2 extranodal sites of involvement; bulky mass > 10 cm or bulky mediastinal mass > 1/3 of mediastina/thoracic ratio; B symptoms; and elevated serum lactate dehydrogenase (LDH) level. The study included 11 men (55%) and 9 women (45%). The median age was 37 years (range 20-57). Seventeen patients (85%) had stage IV disease; 14 (70%) had B symptoms; 13 (65%) had bulky mass > 10 cm; 14 (70%) had > or = 2 extra nodal sites involvement; and eight patients (40%) had elevated LDH levels. All patients were treated with standard four or 7-8 drug combination chemotherapy regimens until they achieved maximal response prior to ASCT with a median of six cycles (range 4-11). Six patients also received involved field radiotherapy to residual bulky mass > 5 cm or bony lesions before ASCT. The median time from diagnosis to ASCT was 8.6 months (range 5.5-18.9). Preparative regimens consisted of fractionated total body irradiation (FTBI) 1200 cGy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg in all patients except one who had borderline pulmonary function and received lomustine 15 mg/kg instead of FTBI. All patients engrafted and there was no transplant-related mortality. One patient developed congestive cardiomyopathy at 4 years post-ASCT. All patients remain alive and in remission at a median follow-up of 42.8 months (range, 13.2-149.2). These preliminary results suggest that HDT and ASCT can be performed safely during first CR/PR in selected patients with advanced-stage HD who have an unfavorable prognosis. Further randomized studies comparing HDT and ASCT during first CR with conventional chemotherapy and ASCT at relapse in poor-risk advanced-stage HD should be conducted. The prognostic factors and risk groups described recently by an international prognostic study can be used to identify high-risk patients who may be candidates for more intensive therapy.
Nademanee
A
A
Department of Hematology and Bone Marrow Transplantation, City of Hope National Medical Center, Duarte, California 91010, USA.
Molina
A
A
Fung
H
H
Stein
A
A
Parker
P
P
Planas
I
I
O'Donnell
M R
MR
Snyder
D S
DS
Kashyap
A
A
Spielberger
R
R
Bhatia
R
R
Krishnan
A
A
Sniecinski
I
I
Vora
N
N
Slovak
M
M
Dagis
A
A
Niland
J C
JC
Forman
S J
SJ
D000328:Adult; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation