High-Dose Therapy with Peripheral Blood Stem Cell Transplantation for Patients with Relapsed or Refractory Hodgkin’s Disease: A Single-Institution 20-Year Follow-up Experience.

Most patients with Hodgkin disease achieve durable remission with radiation therapy, combination chemotherapy, or both. However, patients who relapse after attaining complete remission with chemotherapy and those who have primary refractory disease have a poor outcome with conventional dose salvage chemoradiotherapy regimens. In the past 20 years, several clinical trials using high-dose chemotherapy (HDCT) or chemoradiotherapy with autologous stem cell transplantation have been reported, but only few of them focused on long term outcome, late toxicity and different treatment options after relapse.

From March 1986 to August 2007, 107 patients with relapsed or refractory Hodgkin’s disease underwent HDCT with peripheral blood stem cell transplantation in our center. There were 64 males and 43 females with a median age of 31 years (range 17 – 63 years). For HDCT, 82 patients were treated with CBV (cyclophosphamide, etoposide, carmustine), while 20 patients received BEAM (carmustine, etoposide, cytarabine, melphalan) or other regimens (n=5).

For the entire group, the probabilities of freedom from progression (FFP), overall survival (OS) and event-free survival (EFS) after HDCT were 65%, 61%, and 53% at 10 years, respectively, after a median follow-up of 12.4 years (range, 0.15 – 20.3 years). Notably, no relapse occurred later than 48 months post transplant. Cox analyses identified duration of remission (≤12 versus >12 months) as well as disease status prior to transplantation (complete remission versus partial remission versus stable / refractory disease) as significant prognostic factors for FFP, EFS, and OS.

Early mortality rate (≤100 days) declined from 17.1% to 8.3% after 1992 subsequent to introduction of hematopoietic growth factors for stem cell mobilization. Late mortality rate (>100 days) was 30.8% (n=33), causes of death were Hodgkin’s disease (n=21), secondary malignancies (n=6), fibrosis of the lung (n=3), myocardial fibrosis (n=1), perforated sigmoid diverticulitis (n=1) and septicemia (n=1). The probability of secondary malignancies was 6.4% and 12.1% after 5 and 10 years, respectively.

For the patients relapsing after HDCT (n=33), the median OS was 17.3% at 5 years. We found that patients with a remission time of >6 months after transplantation had a prolonged 5-year OS of 50.3% versus 0% (p=0.03) in patients with remission times of ≤6 months. To date, three of 33 patients live disease-free more than 5 years after relapse. These patients were treated with allogeneic transplantation (n=1), secondary HDCT (n=1) or conventional chemotherapy (n=1), suggesting that different treatment approaches have the potential to rescue individual patients although the overall outcome after HDCT failure is poor.

In conclusion, HDCT can provide long-term disease control in patients who have failed primary therapy for Hodgkin’s disease. Although the results as a whole are encouraging for chemosensitive patients and have improved over time, new therapeutic strategies are needed to reduce toxicity of HDCT and improve the clinical outcome of those patients who relapse after HDCT.