J P-glycoprotein expression in resistant or relapsing Hodgkin?s disease.

Twenty-eight males and 8 females with resistant (10 patients) or relapsing (26 patients) Hodgkin's Disease (HD) after chemotherapy were included in this study. Their ages ranged from 16 to 55 years with a median age of 28±8.3 years. Immunohistochemical staining for detection of p-glycoprotein (Pgp) using monoclonal antibody to multidrug resistance marker, p170 glycoprotein, clone JSB-1-Bio Genex, San Roman, California, USA, was done for all patients at relapse. P-glycoprotein was also studied in tissue specimens of ten of the studied patients at diagnosis as a control group. Salvage chemotherapy was tailored according to initial regimens and duration of the first disease-free survival (DFS1). Patients relapsed after long DFS1 were retreated by the same regimen, while those with primary resistance or short DFS1 were crossed over to another non cross-resistant combination chemotherapy. In the control group, Pgp expression was found in 20% (2/ 10) of patients in the affected nodes at initial diagnosis compared with 90% (9/10) of them at relapse (p = 0.01). For all patients at relapse or resistance, Pgp expression was found in 29 patients (80%) and was more expressed in patients with B-symptoms, primary progressive disease or short DFS1 and histological subtypes other than lymphocyte predominance. Patients with negative Pgp expression had a better overall response (100%) compared with those with positive Pgp expression (72.4%). Pgp overexpression was found to be inversely correlated with 1-year survival. The overall response rate to salvage treatment was 77.8% with 38.9% complete response. Male patients, age above 40, lymphocyte depletion histology, B-symptoms, bulky disease, those with primary resistance or short DFS1 were found to have poor overall response rate. Variables associated with longer response duration after salvage therapy were complete response, long DFS1, negative Pgp expression, young age, female gender, absence of B-symptoms and lymphocyte predominance histology. It was concluded from this study that Pgp overexpression could be a useful prognostic factor in addition to other factors in predicting the response to salvage therapy and survival in patients with relapsing HD.