High-dose therapy and autologous hematopoietic-cell transplantation for follicular lymphoma beyond first remission: The Stanford University experience

A retrospective analysis was performed to investigate the outcome of high-d ose therapy (HDT) and autologous hematopoietic cell transplantation in pati ents with follicular lymphomas beyond first remission. Ninety-two patients with primary induction failure or relapsed follicular low-grade lymphoma (F LGL), follicular large cell lymphoma (FLCL), and transformed follicular lym phoma (TFL) were treated with myeloablative therapy consisting of etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either carmustine (BCNU;15 m g/kg) or fractionated total body irradiation (FTBI; 1200 cGy) followed by t ransplantation of purged autologous bone marrow or peripheral blood hematop oietic cells. For the 49 patients with relapsed FLGL, the median age was 49 years and the median interval from diagnosis to HDT was 30 months. The 4-y ear estimate of overall survival (OS) was 60% (95% confidence interval [CI] , 45%-75%) and of disease-free survival (DFS) was 44% (95% CI, 29%-59%). Tr eatment with the FTBI-containing HDT regimen was associated with significan tly longer DFS (P = .04) and OS (P = .04) in our multivariate analysis. OS was also significantly longer among those treated with 3 or fewer chemother apy regimens. For the 26 FLCL patients, the median age was 51 years and in 31% the indication for HDT was primary induction failure. For FLCL patients , the 4-year estimate of OS was 58% (95% CI, 37%-79%) and of DFS was 51% (9 5% CI, 30%-72%). Among the 17 patients with TFL, 13 (76%) transformed at fi rst relapse, and only 6 patients (35%) achieved complete remission with sal vage therapy prior to HDT. For TFL patients, the 4-year estimate of OS was 50% (95% CI, 24%-76%) and of DFS 49% (95% CI, 20%-78%). There were 3 occurr ences of myelodysplasia (1 after treatment with TBI, 2 after BCNU treatment ), yielding an estimated incidence of 7% (95% CI, 0%-16%) at 56 months. Thi s analysis shows that relapsed FLGL patients treated with 3 or fewer differ ent chemotherapy regimens show inferior survival. The HDT regimen containin g FTBI appears to be superior to the BCNU-based regimen for relapsed FLGL, although longer follow-up is needed to evaluate late effects. Lastly, patie nts with TFL or induction failure and relapsed FLCL can achieve survival ou tcome comparable to those observed with the indolent follicular lymphomas.