Bcl2 Over-Expression as a Prognostic factor In Hodgkin Lymphoma Patients who Required Intensive Treatment

The majority of patients with classical Hodgkinxs Lymphoma (cHL) are cured with primary treatment. However, a significant proportion of patients will not achieve a complete response (CR) or relapse after completion of initial therapy and need to be rescued with high-dose chemotherapy and stem cell transplantation (SCT): autologous (aSCT) and/or alogeneic (Alo-SCT). The identification of clinical and biological characteristics of these patients at diagnosis is still a challenge and the most prognostic systems used to date fail to identify a proportion of patients with worse prognosis. The best understanding of the biology of cHL could help to identify these patients and different groups works in the use of biological marker as determinants of clinical outcome. Bcl2 over-expression has been described in cHL and seems to be an independent marker associated to bad prognosis in probably relation with alterations in apoptosis regulatory molecules.

To retrospectively analyze the frequency of Bcl2 protein over-expression in tissue biopsies of patients diagnosed with cHL, which required intensive treatment in our centre.

We revised clinical data and samples at diagnosis of patients with cHL who received SCT (aSCT or/and Allo-SCT) due to partial remission, relapse or progression and we determined Bcl2 expression protein by immunohistochemistry. All patients received at least 2 lines of treatment previous to intensive treatment with SCT. We analyzed the expression of Bcl2 according to each patient histology: Nodular Sclerosis (NE), Mixed cellularity (MC), Lymphocyte-rich (LR), and Lymphocyte-depleted (LD).

Between September 1997 and May 2010, 39 patients with cHL required intensive treatment in our center: 32 aSCT and 7 Allo-SCT due to partial remission, refractory, relapse or progression after first line of treatment. Average age was 32 years (range: 18–64), males: 25/females 14. The characteristics of patients and remission status at transplant are described in table 1. We had available samples at diagnosis from 31 out of 39 patients (80%): 20 NE, 5 MC, 6 LR and we found over-expression of Bcl2 in 17/20 (85%) NE; 5/5(100%) MC and 2/6 LR (33%).

Our results suggest that over-expression of Bcl2 is frequent in patients with cHL which needed intensive treatment after failure of the first line of therapy (particularly with NE and MC). Further studies are needed to confirm the worse prognosis of Bcl2 expression in cHL and if may be useful at diagnosis in association with other clinical parameters to identify patients with poor prognosis.

Alo-SCT: Alogeneic stem cell transplant; aSCT: autologous stem cell transplant; CR: Complete Remission; F: female; LD: Lymphocyte-deplete; LR: Lymphocyte rich; M: male; MC: mixed cellularity Md: median; n: number; NE: nodular sclerosis; Nv: negative; P: positive; PR: Parcial remision R: range; RF: refractory

No relevant conflicts of interest to declare.