High-Dose Sequential Chemotherapy (HDSC) in Support of Autologous Stem Cell Transplantation (ASCT) in Patients with Relapsed/Refractory Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL).

Background and aim: High-dose chemotherapy followed by ASCT is currently the standard treatment in achieving long-term survival in patients with relapsed or refractory HL and NHL. The aim of the present study is to assess the role of HDSC and ASCT in attaining high survival rates in patients with relapsed or refractory lymphoma.

Patients and Method: From 2000 to 2004, 42 patients with relapsed/refractory HL or NHL with a median age of 42 years (M:F=28:14) were treated with HDSC and ASCT. Only patients who were sensitive to salvage chemotherapy were eligible for the protocol, consisting of 3 phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF (10 mcg/kg/d) and PBSC collection. Phase II consisted of etoposide (2 g/m2) with G-CSF support of at 5 mcg/kg/d. The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by APBSC infusion.

Results: NHL patients had diffuse large cell (n=16), anaplastic large cell (n=4), mantle cell (n=2), follicular (n=2), small lymphocytic (n=2) and peripheral T cell (n=2) histology. Patients with HL had mixed cellular (n=7) and nodular sclerosing (n=7) histology. The rationale for ASCT was first relapse in 17 (41%) patients, more than one relapse in 14 (33%) patients, primary refractory disease in 10 (24%) patients and high risk disease in 1 (2%) patient. Prior to HDSC, 69% and 31% of the patients were in CR and PR, respectively. Patients received a median of 5.3x106/kg CD34+ cells. Median times to achieve neutrophil and platelet engraftments were 14 and 24 days, respectively. Transplant related mortality rate was 7% (n=3). At a median follow-up of 26 months (range, 1–48), 10 patients relapsed and 12 patients died. Causes of mortality were; veno-occlusive disease (n=1), infection (n=3), progression/relapse (n=6), congestive heart failure (n=1) and secondary AML (n=1). Five patients developed congestive heart failure (severe in one patient), mainly due to high cumulative doses of anthracyclines during the previous therapies. The estimated 3-year disease-free survival (DFS) and overall survival (OS) were 66.7% and 69.2% in HL patients and 75% and 77.4% in NHL patients, respectively. Regarding DFS and OS, there was no statistically significant difference between HD and NHL. Currently, 30 (71%) of patients are alive, of which 28 (67%) patients are in complete remission.

Conclusion: HDSC followed by APBSCT is an effective therapy in patients with relapsed/refractory NHL or HD, with an acceptable mortality rate.