About 20%-50% of patients with stage IV Hodgkins disease may suffer a relapse after initial chemotherapy-induced remission. Consolidative radiotherapy has been used in combination with chemotherapy to reduce relapse at areas of initial bulky disease; however, no survival benefit has been shown in the few randomized studies.
The purpose of this study was to evaluate the role of high-dose therapy and autologous stem-cell transplantation (SCT) in the treatment of patients with stage IV Hodgkins disease and to evaluate the impact of prior radiotherapy on the outcome of autologous SCT. A retrospective analysis was performed in 65 patients with stage IV Hodgkins disease who underwent autologous SCT at our institution between February 1987 and August 1997. There were 35 (54%) males and 30 (46%) females, with a median age of 32 years (range, 14-60 years). At diagnosis, 55 (85%) of patients had B-symptoms, 39 (60%) had bone marrow or lung involvement, 12 (18%) had ³ 2 extranodal sites, and 16 (34%) had hemoglobin < 10.5 g/dL. Disease status at transplant was: first complete response (CR)/partial response (PR) in 17 (26%) patients, induction failure (IF) in 12 (18%), and relapse or ³ 2 CRs in 37 (56%). The median number of chemotherapy regimens was two (range, one to three), and 27 (42%) of patients had received prior radiation therapy, including 20 as induction therapy and 7 as salvage therapy. Median time from diagnosis to SCT was 18 months (range, 5-199 months). For patients transplanted in relapse or IF, 19 had extranodal involvement at conditioning, including 10 with bone marrow or lung involvement, and 8 had ³ 2 extranodal sites.
The conditioning regimens were either fractionated total-body irradiation (1,200 cGy) in 42 patients (65%), or carmustine(Drug information on carmustine) (450 mg/m2) in 23 patients (35%), in combination with etoposide (60 mg/kg) and cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar; 100 mg/kg). Currently, 37 patients are alive in remission, 19 have relapsed (13 died), and 9 have died from transplant-related complications. The median follow-up for all living patients is 3.9 years (range, 1.0-11.5 years). The median time to relapse was 6.8 months (range, 1.6-42.9 months). The 3-year Kaplan-Meier overall survival (OS), disease-free survival (DFS), and relapse rates for all patients were 74% (95% confidence interval [CI], 61%-83%), 63% (95% CI, 51%-74%), and 27% (95% CI, 17%-40%), respectively. None of the patients transplanted in first CR/PR have relapsed. The 3-year DFS for patients transplanted in first CR/PR was 100%, compared with 55% (95% CI, 26%-80%) for IF and 50% (95% CI, 37%-66%) for relapsed patients (P = .001; log-rank test).
By univariate survival analysis, disease status at transplant predicted for relapse (P = .02), DFS (P = .003), and OS (P = .02); bone marrow or lung involvement had a negative impact on DFS (P = .05); and extranodal sites at SCT and prior radiation both increased the risk of relapse (P = .02 and .04, respectively). By stepwise Cox regression analysis, prior radiation remained a significant predictor for relapse (P = .04; risk ratio, 2.79 [95% CI, 1.05-7.46]). When disease status at SCT was not included in the model, both the number of prior regimens and bone marrow or lung involvement predicted for DFS (P = .05 for both).
CONCLUSION: We conclude that: (1) high-dose therapy plus autologous SCT is an effective salvage therapy for patients with stage IV Hodgkins disease who have relapsed or have primary refractory disease; (2) in this analysis, patients with prior radiotherapy are at risk for relapse after autologous SCT; and (3) the outcome of autologous SCT is best when performed during first remission in unfavorable advanced-stage Hodgkins disease