Kinetics of early therapeutic response as measured by quantitative PCR predicts survival in a murine xenograft model of human T cell acute lymphoblastic leukemia.
The identification of prognostic parameters and surrogate markers for defining patient risk has been beneficial in effectively guiding therapy and increasing the survival of leukemia patients. It has been hypothesized that the therapeutic response, as measured by a change in tumor burden during therapy, might serve as a new surrogate marker of survival. Here we describe the development of a murine SCID xenograft model of human T cell acute lymphoblastic leukemia (T-ALL), and the use of a sensitive, quantitative PCR assay for the measurement of tumor levels to investigate the relationships between tumor burden quantification, therapeutic response and survival. Animals engrafted with the CCRF-CEM (CEM) human T-ALL cell line develop leukemia that closely resembles the human disease. Quantitative PCR detects the expanding tumor mass in the peripheral blood of the animals several weeks before death. In response to induction therapy with chemotherapeutic agents, both the level of minimal residual disease (MRD) in peripheral blood at the end of therapy and the rate of tumor reduction in peripheral blood during therapy strongly correlated with animal survival. Thus, these surrogate markers, which can be measured during the early stages of therapy, may help improve patient survival through dynamic risk stratification.
Department of Pathology and Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas 75390-9072, USA.
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Hosler
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Scheuermann
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002138:Calibration; D002453:Cell Cycle; D003520:Cyclophosphamide / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000235:genetics*; D004317:Doxorubicin / Q000627:therapeutic use; D004341:Drug Evaluation; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012015:Reference Standards; D018570:Risk Assessment; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D008727:Methotrexate