Drug induction apoptosis assay as predictive value of chemotherapy response in patients with B-cell chronic lymphocytic leukemia

• Published in: Leukemia & lymphoma Vol. 50; no. 4; pp. 593 - 603
• Main Authors: Castejón, Raquel, Yebra, Miguel, Citores, María-Jesús, Villarreal, Mercedes, García-Marco, José A., Vargas, Juan A.
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01-01-2009; Taylor & Francis
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; apoptosis induction assay; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; chemotherapy; Chlorambucil - pharmacology; Chronic lymphocytic leukemia; Cladribine - pharmacology; Female; Flow Cytometry; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Male; Middle Aged; Predictive Value of Tests; Prognosis; Time Factors; Tumor Cells, Cultured; Vidarabine - analogs & derivatives; Vidarabine - pharmacology
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428190902780669

A large number of prognostic factors are available to help predict the course of the disease for patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear the involvement of these well established prognostic factors in the clinical response of the patients with B-CLL to the chemotherapy. The possible association of the patient clinical-biological characteristics and the in vitro response to chemotherapic agents may serve to provide powerful predictive information to identify optimum treatment for patients. An apoptosis induction assay displays the patient in vitro responses to chemotherapy and the possible association with their clinical-biological characteristics. In this study, patients showed a significant better in vitro response to drugs when they were in the initial stages of the disease or with low β2 microglobulin serum level. Response to purine analogues was significantly higher in patients with long lymphocyte doubling time (LDT), few cells expressing CD38, normal karyotype or no p53 deletion, whereas there was no correspondence with ZAP-70 expression. Furthermore, a good correlation was shown between in vitro apoptosis induction assay and the patient clinical response to purine analogues. In conclusion, association between in vitro drug sensitivity and some of the markers considered as prognostic factors could help to develop personalised therapeutic regimens for patients with B-CLL.