2008HaematologicaOpen access

Pharmacokinetics of alemtuzumab in combination with fludarabine in patients with relapsed or refractory B-cell chronic lymphocytic leukemia

Thomas Elter, Julia Kilp, Peter Borchmann, H. Schulz, Michael Hallek, Andreas Engert

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Abstract

MDM2 SNP 309 can lead to earlier onset or more advanced disease 6 and TP53 negatively regulates MDM2 expression, we assessed MDM2 SNP 309 alleles in isolation or in combination with TP53 Arg72Pro alleles against these clinical parameters; there was no evidence of any association (illustrated in Table 1 for gender, stage and responses to therapy; p≥0.13).Kaplan-Meier plots and log rank test statistics demonstrated no evidence for association of MDM2 SNP 309 or TP53 Arg72Pro allelic variants alone, or in combination, with overall survival (Figure 1A), progression free survival, relapse free survival or time to transformation (Figure 1B) (p≥0.17).Consequently, whilst genomic lesions targeting the MDM2-TP53 axis are an important feature of FL, MDM2 SNP 309 and TP53 Arg72Pro do not predict clinical outcome.In contrast to other malignancies these polymorphisms are not significant in FL.

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MDM2 SNP 309 can lead to earlier onset or more advanced disease 6 and TP53 negatively regulates MDM2 expression, we assessed MDM2 SNP 309 alleles in isolation or in combination with TP53 Arg72Pro alleles against these clinical parameters; there was no evidence of any association (illustrated in Table 1 for gender, stage and responses to therapy; p≥0.13).Kaplan-Meier plots and log rank test statistics demonstrated no evidence for association of MDM2 SNP 309 or TP53 Arg72Pro allelic variants alone, or in combination, with overall survival (Figure 1A), progression free survival, relapse free survival or time to transformation (Figure 1B) (p≥0.17).Consequently, whilst genomic lesions targeting the MDM2-TP53 axis are an important feature of FL, MDM2 SNP 309 and TP53 Arg72Pro do not predict clinical outcome.In contrast to other malignancies these polymorphisms are not significant in FL.

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Available abstract

MDM2 SNP 309 can lead to earlier onset or more advanced disease 6 and TP53 negatively regulates MDM2 expression, we assessed MDM2 SNP 309 alleles in isolation or in combination with TP53 Arg72Pro alleles against these clinical parameters; there was no evidence of any association (illustrated in Table 1 for gender, stage and responses to therapy; p≥0.13).Kaplan-Meier plots and log rank test statistics demonstrated no evidence for association of MDM2 SNP 309 or TP53 Arg72Pro allelic variants alone, or in combination, with overall survival (Figure 1A), progression free survival, relapse free survival or time to transformation (Figure 1B) (p≥0.17).Consequently, whilst genomic lesions targeting the MDM2-TP53 axis are an important feature of FL, MDM2 SNP 309 and TP53 Arg72Pro do not predict clinical outcome.In contrast to other malignancies these polymorphisms are not significant in FL.

Key concepts: Alemtuzumab, Fludarabine, Chronic lymphocytic leukemia, Medicine, Monoclonal antibody, Monoclonal, Oncology, Refractory (planetary science)

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