| High dose chemoradiotherapy and ASCT may overcome the prognostic importance of biologic markers in relapsed/refractory Hodgkin lymphoma. | |
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MedLine Citation:
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PMID: 19701081 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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INTRODUCTION: Of about 20% of patients with relapsed/refractory Hodgkin lymphoma (HL), approximately half achieve long-term remissions after high-dose chemoradiotherapy and autologous stem cell transplantation (HDT/ASCT). Treatment with a comprehensive program using second-line chemotherapy with ICE (ifosfamide, carboplatin, etoposide) before HDT/ASCT identified a clinical prognostic model, but prognostic biologic markers in relapsed/refractory HL remain unclear. We sought to determine if we could identify such markers, and if our comprehensive second-line program could overcome their significance. METHODS: Pre-ICE biopsy specimens of 191 patients enrolled on 1 of 2 Institutional Review Board-approved clinical trials of HDT/ASCT. We performed immunohistochemistry staining for Bcl-2, Bax, Bim, p53, and interleukin-6. Samples were considered positive if more than 10% of Hodgkin Reed-Sternberg cells stained at any intensity. RESULTS: Ninety-one patients had sufficient tissue available. Forty-eight patients (53%) had an event and 36 (40%) died. Median event-free survival (EFS) was 8.5 years, median overall survival (OS) was not reached, and median follow-up was 8.8 years. Bcl-2 was overexpressed in 37/91 (41%), Bax in 28/65 (43%), Bim in 9/72 (13%), p53 in 38/89 (43%), and interleukin-6 in 58/84 (69%) patients. Overexpression of these biomarkers had no statistically significant association with EFS or OS, except for association of Bim overexpression with inferior OS (P = 0.0385). The 3-factor clinical model (B symptoms at relapse, extranodal disease, and complete remission duration of < 1 y) remained highly significant (0/1 vs. 2/3 factors) for EFS and OS (P = 0.0008 and P = 0.0001, respectively). CONCLUSIONS: Despite the evidence that p53 and Bcl-2 overexpression may predict a worse prognosis with initial treatment, it seems that at relapse such overexpression is either not prognostically significant, or that the treatment with ICE and HDT/ASCT overcomes its significance. Subsequent studies should further address the role of Bim in both initial and relapsed/refractory settings. |
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Authors:
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Daniel O Persky; Craig H Moskowitz; Alexander Filatov; Rakhee Saxena; Haiyan Cui; Julie Teruya-Feldstein |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry Volume: 18 ISSN: 1533-4058 ISO Abbreviation: Appl. Immunohistochem. Mol. Morphol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-23 Completed Date: 2010-04-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888796 Medline TA: Appl Immunohistochem Mol Morphol Country: United States |
Other Details:
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Languages: eng Pagination: 35-40 Citation Subset: IM |
Affiliation:
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Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Apoptosis Regulatory Proteins / analysis Carboplatin / therapeutic use Combined Modality Therapy / methods Etoposide / therapeutic use Hematopoietic Stem Cell Transplantation / methods Hodgkin Disease / diagnosis, mortality, therapy* Humans Ifosfamide / therapeutic use Immunohistochemistry Membrane Proteins / analysis Middle Aged Prognosis Proto-Oncogene Proteins / analysis Proto-Oncogene Proteins c-bcl-2 / analysis Salvage Therapy / methods* Transplantation, Autologous Tumor Markers, Biological / analysis Tumor Suppressor Protein p53 / analysis Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Markers, Biological; 0/Tumor Suppressor Protein p53; 33419-42-0/Etoposide; 3778-73-2/Ifosfamide; 41575-94-4/Carboplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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