Cyclophosphamide, Gemcitabine, Vinorelbine and Prednisone (CGEV) As Salvage Therapy for Relapsed or Refractory Hodgkin´s Lymphoma before Hematopoietic Stem Cell Transplantation: A Single Center Experience

Background and Objectives: 

Although the therapy of advanced-stage Hodgkin Lymphoma (HL) has improved, up to 10% of patients with advanced-stage HL will not achieve complete remission (CR) with standard therapy, and 20%–30% of responders will relapse after treatment. 

The disease status before autologous stem cell transplantation remains the most important factor predicting outcome for patients with relapsed or refractory HL. The IGEV regimen (Ifosfamide, gemcitabine, vinorelbine and prednisolone) is a good option for salvage induction therapy before autologous stem cell transplantation, with a reported overall response rate of 81%. Due to the high cost of the IGEV regimen, and the financial constrains of our population, we decided to modify the original regimen using cyclophosphamide instead of ifosfamide. 

Design and methods: 

From January 2011 to January 2015, 19 patients with relapsed or refractory HL received the protocol consisting of four cycles of cyclophosphamide, gemcitabine, vinorelbine and prednisone (CGEV). It was administrated in outpatient setting. The CGEV regimen consists of cyclophosphamide 600 mg/m2 on days 1 to 3, gemcitabine 800 mg/m2 on days 1 and 4, vinorelbine 20 mg/m2 on day 4, prednisone 100 mg on days 1 to 4 and granulocyte colony-stimulating factor (G-CSF) from day 7 to 12 of each course. Four courses of chemotherapy were planned before autologous stem cell transplantation, after the third course, autologous peripheral blood stem cells (PBSC) were collected. 

Results: 

Nineteen patients with primary refractory or relapsed HL received the CGEV regimen. There were 10 males and 9 females. Nodular sclerosis was the most frequent histological subtype in 73%. At diagnosis, there were 7 (36%) patients in clinical stage IV and 12 (63%) in early stage I-II. The lungs were the most frequent extranodal organ involved. B symptoms were present in 9 (47%) patients. All our patients received as first line chemotherapy the regimen ABVD, the disease status before salvage induction chemotherapy with CGEV was: 9 (47%) patients with refractory disease and 10 (53%) patients were in relapse. The median number of cycles administrated was 4 (1-4). Only 14 patients received the total planned courses. 

The overall response to the CGEV regimen was 78%, of these, 6 (42.8%) patients achieved complete response and 5 (35.7%) partial response. 

Ten patients underwent autologous stem cell mobilization, obtaining an adequate CD34+ cell collection in all the patients. The median number of CD34+ cell was 9.08 x 106/kg (2.1-5.60 x 106/kg) with a median of 1 apheresis procedure. 

Hematologic grade 3 and 4 toxicity developed in 11 (59%) patients, no grade 4 extra-hematologic toxicity was observed. There were 3 treatment-related infections. Four patients died, 2 due to septic shock, and 2 with disease progression. 

Interpretation and conclusions: 

We describe a similar overall response rate of 78% with CGEV regimen compared with the 81% reported with IGEV regimen, it is less expensive and can be used in relapsed or refractory patients with HL, as salvage regimen before autologous stem cell transplantation.