Abstract |
Although chromosome 17p abnormalities and TP53 mutations have been reported as poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not been defined in patients with CLL treated with chemoimmunotherapy, particularly in the context of other novel markers such as ZAP-70 expression and IgVH mutation status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed in 208 and 108 patients, respectively. One hundred sixty-eight patients had concurrent classical cytogenetic analysis. p53-IHC correlated with abnormal karyotype (p = 0.002) and adversely affected overall survival independent of ZAP70 expression and IgVH MS (p < 0.001). Patients with p53-IHC(+) CLL were less likely to achieve complete remission, but patients who did achieve complete remission showed a durable response. In this patient cohort, p53-IHC is an important determinant of complete remission and overall survival, but not remission duration, in patients with CLL receiving FCR.
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Authors | Ellen J Schlette, Joan Admirand, William Wierda, Lynne Abruzzo, Katherine I Lin, Susan O'Brien, Susan Lerner, Michael J Keating, Constantine Tam |
Journal | Leukemia & lymphoma
(Leuk Lymphoma)
Vol. 50
Issue 10
Pg. 1597-605
(Oct 2009)
ISSN: 1029-2403 [Electronic] United States |
PMID | 19863337
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Murine-Derived
- Biomarkers, Tumor
- Tumor Suppressor Protein p53
- Rituximab
- Cyclophosphamide
- ZAP-70 Protein-Tyrosine Kinase
- ZAP70 protein, human
- Vidarabine
- fludarabine
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
(administration & dosage)
- Antibodies, Monoclonal, Murine-Derived
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology, therapeutic use)
- Biomarkers, Tumor
(analysis, genetics)
- Bone Marrow Examination
(methods)
- Combined Modality Therapy
- Cyclophosphamide
(administration & dosage)
- Female
- Follow-Up Studies
- Gene Expression Regulation, Leukemic
- Genes, p53
- Humans
- Immunohistochemistry
- Leukemia, Lymphocytic, Chronic, B-Cell
(drug therapy, genetics, mortality, pathology)
- Male
- Middle Aged
- Prognosis
- Rituximab
- Somatic Hypermutation, Immunoglobulin
(genetics)
- Survival Analysis
- Tumor Suppressor Protein p53
(analysis, biosynthesis)
- Vidarabine
(administration & dosage, analogs & derivatives)
- Young Adult
- ZAP-70 Protein-Tyrosine Kinase
(analysis)
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