| Abstract: |
SUMMARY AND CONCLUSIONNHLs include a large number of lymphoid neoplasms that can now be recognized on basis of morphologic, immunophenotypic and genetic features.Nm23H1 has been shown to negatively correlate with tumor metastasis, to support endocytosis, to act as a histidine kinase and to nick DNA during cytotoxic T lymphocyte induced apoptosis.5-10% of patients with aggressive NHLs do not respond to induction therapy, 5-15% of patients with aggressive NHLs achieve only a partial response and 20-40% of patients with aggressive NHLs who achieve initial CR subsequently develop recurrent diseases and likelihood of relapsing from CR varies depending on patients initial risk profile.This study had been carried out in Medical Oncology and Hematology Unit, Internal Medicine Department, Zagazig University Hospital, between Jan. 2002 and Jul. 2004, on 30 patients with chemotherapy naïve aggressive NHLs and 30 relapsed aggressive NHLs (of diffuse large cell type) with 10 healthy subjects as a control.Each patient was subjected to complete history, complete physical examination, staging “according to Ann Arbor staging system”, routine laboratory investigations and evaluation of nm23H1 in serum by ELISA.Patients with chemotherapy naïve aggressive NHLs were treated by CHOP protocol and relapsed aggressive NHLs were treated with DHAP protocol. After 3 cycles all patients were re-evaluated and responding patients continued for 6-8 cycles of CHOP or 6 cycles of DHAP then response was evaluated. All patients were followed up for 2 years from randomization to evaluate DFS and OS.Our results showed that:• The response to CHOP protocol in chemotherapy naïve patients were CR after 6 cycles was 66.7%, PR was 13.3% (OR was 80%) and NR was 20%.• The response to DHAP protocol after 6 cycles in relapsed aggressive NHLs were CR was 56.7%, PR was 16.6% (OR was 73.3%) and NR was 26.6%.• Comparison between cases and control in serum nm23H1 where there is a statistically significant difference.• The stage (III-IV), PS (2 or more according to ECOG), extra nodal (2 or more sites), IPI (>2), presence of B- symptoms, bulky disease (>10cm in diameter), BM involvement, response to chemotherapy, low s. albumin(<3.5 gm%) and Hb level (10 gm% or less) were statistically significant associated with markedly elevated nm23H1 level (p<0.05) in chemotherapy naïve aggressive NHLs.• The age (more than 60 years), stage (III-IV), IPI (>2), BM involvement, response to chemotherapy, and Hb level (10 gm% or less) were statistically significant associated with markedly elevated nm23H1 level (p>0.05) where presence of B-symptoms and low s. albumin(<3.5 gm%) were borderline significant in relapsed aggressive NHLs.• The age (more than 60 years), stage (III-IV), PS (2 or more according to ECOG), extranodal (2 or more sites), IPI (>2), presence of B-symptoms, bulky disease (>10cm in diameter), BM involvement, low s. albumin(<3.5 gm%) and Hb level (10 gm% or less) are statistically significant associated with poor response to chemotherapy (p<0.05) in chemotherapy naive aggressive NHLs group.• The age (more than 60 years), IPI (>2), BM involvement, and Hb level (10 gm% or less) are statistically significant associated with poor response to chemotherapy (p<0.05) where PS (2 or more according to ECOG) was borderline significant (p=0.08) relapsed aggressive NHLs group.• Only nm23H1(80ng/ml or more) and advanced stage (III-IV) were significantly and independently affecting DFS in all patients and only nm23H1 (80ng/ml or more), presence of B-symptoms and B.M involvement were significantly and independently affecting OS in all patients.RECOMMENDATIONS• Evaluation of pretreatment nm23H1 by ELISA is a simple and informative to evaluate nm23H1 in NHLs a prognostic factor but further large randomized studies are needed.• In future, we hope that more useful prognostic factors can be defined by studying more cases. Also its important to study nm23H1 in NHLs for further analysis of its function in lymphomas, because there is still many questions with regard to the functions of nm23H1.• Development of a new prognostic index based on actual measures of drug resistance including: clinical variables, biological and molecular markers then patients with adverse prognostic features should be subjected to new strategies of therapy to improve the results obtained.• But, if progress can be made, the evaluation of new treatments will need randomized studies with large number of patients and a prolonged follow up.
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