Single or Tandem Autologous Stem-Cell Transplantation Given According to Prognostic Factors at Relapse for Hodgkin Lymphoma.

Patients with relapsed hodgkin lymphoma (HL)have a different prognostic after high-dose therapy (HDT)according to time to relapse and extend of relapse. From 1995 to 1997, 48 patients with early relapse or refractory HL were included in a pilot study of tandem transplantation to evaluate the feasibility before the protocol. From 1998 to 2002, 200 patients with refractory disease or first relapse of HL were prospectively treated with induction chemotherapy followed by HDT and autologous stem-cell transplantation (ASCT). Patients were stratified in 2 groups according to prognostic factors at relapse: groupe 1 (unfavorable relapse: primary refractory disease or early/disseminated relapse) and group 2 (favorable relapse: patients with either early or disseminated relapse). Induction chemotherapy consisted of ifosfamide/etoposide with doxorubicin (IVA) in 70% of patients or with vinorelbine and mitoguazone (MINE)for the remainings. Group 1, patients received 2 cycles of chemotherapy, PBSC collection and tandem ASCT, with a CBV mitoxantrone (30 mg/m2) and 2 months later cytarabine (6g/m2), melphalan (140mg/m2)with total body irradiation (40%) or busulfan (12 mg/kg) followed by the second ASCT.

Group 2, patients received 3 cycles of chemotherapy, PBSC collection and a BEAM regimen followed by ASCT. Final results, updated, January 2005 are presented with 245 evaluable patients.

Results: after induction chemotherapy overall response rate was at 61% in group 1 and 96% in group 2. In group 1, 70% received the two ASCT, the major reason not to receive the procedure was disease progression after induction chemotherapy (10%) or after the first ASCT (15%), than low stem-cell collection (4%) or toxicity (2%). In group 2, 97% of patients received ASCT and 1 patient received a tandem ASCT for refractory relapse. 5 patients died from toxicity in group1 and none in group2, but 2 secondary leukemia were observed in this group. In intent to treat analysis, at a 3 years median follow-up from the relapse, the EFS was at 45% in group 1 versus 75% in group 2 and the survival at 55% in group 1 versus 80% in group 2. Despite a different consolidation between group 1 and 2, results remained better in group 2. In conclusion, these results confirmed the importance of prognostic factors at relapse of HL.No differences were found in the unfavorable group 1 between refractory patients and early/disseminated relapse. HL patients with adverse prognostic factors (group 1) but responding to second line chemotherapy and eligible for tandem ASCT may benefit from this procedure with an EFS at 70%. The major cause of failure was chemoresistance either at induction or after high-dose therapy.