pY-STAT3 and p53 expression predict outcome for poor prognosis diffuse large B-cell lymphoma treated with high dose chemotherapy and autologous stem cell transplantation.
The purpose of this study was to evaluate the ability of biomarkers to predict 5-year event-free survival (EFS) of poor prognosis patients with diffuse large B-cell lymphoma (DLBCL) who were treated on a prospective clinical trial with upfront high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). We previously reported 51 patients with DLBCL treated with one cycle each of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP), and carmustine, etoposide, Ara-C, and melphalan (BEAM)/ASCT. Of these patients, 33 had DLBCL and suitable tissue for immunohistochemical (IHC) biomarker evaluation. We found no statistically significant association between EFS and age adjusted International Prognostic Index (IPI) score, bulk over 10 cm, germinal center B-cell phenotype, or expression of BCL-2 or BCL-6 biomarkers. However, the detection of pY-STAT3 expression was associated with improved 5-year EFS (93%versus 47%, p = 0.006), and p53 expression was associated with lower 5-year EFS (47%versus 83%, p = 0.025). Predictive ability was improved by combining pY-STAT3 and p53 expression. Specifically, 5-year EFS rates were 93% for pY-STAT3+, 77% for pY-STAT3-/p53-, and 20% for pY-STAT3-/p53+ patients (p = 0.0002). In conclusion, pY-STAT3 and p53 expression may help predict outcome of HDCT for DLBCL, and further study of these biomarkers is warranted.
Stewart
Douglas A
DA
Department of Oncology and Medicine, University of Calgary and Tom Baker Cancer Centre, Calgary, AB, Canada. douglast@cancerboard.ab.ca
Bahlis
Nizar
N
Mansoor
Adnan
A
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D011034:Podophyllotoxin / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D011499:Protein Processing, Post-Translational; D050796:STAT3 Transcription Factor / Q000032:analysis* / Q000737:chemistry; D014182:Transplantation, Autologous; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014750:Vincristine / Q000008:administration & dosage
D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine; D019000:Phosphotyrosine; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine; D011241:Prednisone