HD Chemoradiotherapy and ASCT Can Overcome the Prognostic Importance of Bcl-2, Bim, and p53 in Relapsed/Refractory Hodgkin’s Lymphoma

Aim:
Prior studies showed that overexpression of bcl-2 and p53 have negative impact on outcome with primary therapy. The study sought to determine if the comprehensive second-line program could overcome these poor prognostic features.

Conclusions:
Researchers concluded that despite the evidence that p53 and bcl-2 overexpression may predict a worse prognosis with initial treatment, it appears that the approach of incorporating ICE and HDT/ASCT may overcome the significance of these biological
markers at relapse.

Official Title

Conditions

Study Type

Study Design

Immunohistochemistry staining for bcl-2, bim (a bcl-2 family marker), were performed on biopsy tissue p53; samples were considered positive if any Reed-Sternberg (RS) cells stained for bcl-2 or bim, and if more than 50% stained for p53, at any staining intensity.

Further Details

Treatment:At MSKCC, ICE (ifosfamide, carboplatin, etoposide) is incorporated as second-line chemotherapy prior to HDT/ASCT in a comprehensive treatment program.About 50% of relapsed patients achieved long-term remissions after high-dose chemoradiotherapy and autologous stem cell transplantation (HDT/ASCT).Results: Median PFS was 4.8 years, median OS was not reached, and median follow-up was 5.7 years. Bcl-2 was overexpressed in 19(27%), bim in 22 (32%), and p53 in 20 (29%) patients. Expression of bcl-2, bim, or p53 had no significant association with PFS or OS. Five-year PFS rates for positive vs. negative cases were 52.6% vs 50% for bcl-2, 54.5% vs 50% for bim, and 50% vs 51% for p53 (all p=NS). The 3 factor clinical model (B symptoms at relapse, extranodal disease and complete remission duration of less than 1 year) remained highly significant (0/1 vs 2/3 factors) for PFS and OS (p=0.002 and p=0.0003, respectively).

Study Start

Eligibility & Criteria

Indication: Relapsed/Refractory Hodgkin’s Lymphoma

Total Enrolment

71 patients had sufficient tissue available. 35 patients (49%) had disease progression and 28 (39%).

Contact Details

Abstract 2073 ASH 2005Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA