A 2-step comprehensive high-dose chemoradiotherapy second-line program forrelapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with high-dose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%, Unfortun ately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Resul ts of a comprehensive a-step protocol encompassing dose-dense and dose-inte nse second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty -five consecutive patients, 22 with primary refractory HD and 43 with relap sed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE), Peripheral blood progenitor cells from responding patient s were collected, and the patients were given accelerated fractionation inv olved field radiotherapy (IFRT) followed by cyclophosphamide etoposide and either intensive accelerated fractionation total lymphoid irradiation or ca rmustine and ASCT. The EFS rate at a median follow-up of 43 months, as anal yzed by intent to treat, was 58%, The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%, Cox regressio n analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission durati on of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 fact ors (P < .001), These results compare favorably with other series and docum ent the feasibility and efficacy of giving uniform dose-dense and dose-inte nse cytoreductive chemotherapy and integrating accelerated fractionation ra diotherapy into an ASCT treatment program, This prognostic model provides a basis for risk-adapted HDT. (C) 2001 by The American Society of Hematology .