Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma:: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG)

Background: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). Patients and methods: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). Results: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P < 0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P = 0.0127) were prognostic factors for FF2F. Response after DHAP (P < 0.0081), duration of first remission (P = 0.0017) and anemia (P = 0.019) were significant for OS. Conclusion: Based on the promising results of this study, a prospective randomized European inter-group study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).