Evaluation of p53 in relapsed and refractory aggressive nhl and response to dhap protocol

Abstract EN

Forty patients with relapsed / refractory aggressive non-Hodgkin's lymphomas (NHLs) of diffuse large cell type were included in the study.

All patients were subjected to complete history taking, physical examination, routine laboratory and radiological investigations for proper staging and evaluation of p53 by immunohistochemistry.

All patients were treated with DHAP protocol "cisplatin 100 mg / m2 D1 C.I.

over 24 hours, cytosine arabinose 2 gm / m2 over 3 hours every 12 hours D2 and dexamethasone 40 mg I.V.

/ day for four days from D1 to D4".

Evaluation was carried out after two cycles and responding patients continued for 6 cycles.

Our results showed that DHAP protocol induced complete response (CR) in 37.5 % of patients, partial response (PR) in 22.5 % of patients and no response (NR) in 40 % of patients.

P53 expression by immunohisto-chemistry was positive in 47.5 % patients of relapsed / refractory aggressive NHLs and more prevalent in old patients (≥ 60 years) poor performance status (PS) and high LDH.

Also, P53 expression was a good predictor for poor response ; the results showed that there was an independent association of P53 with drug resistance along with performance status and age.

Only old age (≥ 60 years) high LDH, poor performance status, short time of disease duration before starting salvage therapy and refractory disease to initial protocol (s) were statistically significant in predicting poor response.

Toxicity to DHAP protocol was acceptable except for hepatic toxicity which terminated the protocol in 12 % of patients and delayed chemotherapy in 20 % of cases due to HCV infection.

In conclusion DHAP protocol provides effective short term therapy in relapsed / refractory aggressive NHLs but further advances in high dose chemo radiotherapy will be necessary for long-term survival.

Assessment of P53 mutations and expression as well as other genes related to P53 such as P21 WAF1 / CIPI and MDM2 are needed for evaluation of the actual P53 gene status.