Aim: Imatinib is considered as the first-line drug of choice for the treatment of CML who is positive for Philadelphia chromosome. To correlate various prognostic scores (Sokal, Hasford and Eutos) and pharmacogenetic markers like ABCG2 421 C>A, SLC22A1 1386C>A, SLC22A1 1022C>T, SLC22A1 1222A>G, ABCB1 3435T>C, ABCB1 2677 G>T/A with the overall and progression-free survival in CML patients.

Methods: The patients who were started on imatinib from December 2009 to January 2014 at Regional Cancer Centre (RCC), JIPMER, Puducherry, India were recruited into the study. DNA was extracted from peripheral blood using phenol-chloroform method. The genotype status was identified using RT-PCR technique (AB7300, Applied Biosystems) using validated SNP genotyping kits. The influence of various factor on OS and PFS was determined using log-rank test (SPSS Ver 20.0).

Results: A total of 119 patients was identified as BCR/ABL positive and started on Imatinib treatment. Out of this 113 patients were in Chronic phase and six were in Accelerated phase. The median age of the patient group wad 39 years (18-74). The median overall survival and progression-free survival was found to be 25 months and 19 months respectively. The three yr overall survival was 94.5%. None of the prognostic scores or genotypes correlated with progression-free survival of the patients in this study cohort. The low-risk category of Sokal and Hasford groups had a statistically better overall survival compared to intermediate and high-risk groups (p value 0.030 and 0.014 using log-rank test analysis). The Mutant alleles for MDR1 C3435T had a better overall survival compared to other genotypes (p value <0.001 using log-rank test).

Conclusion: The Sokal score and Hasford score, not the Eutos score were better predictors of overall survival in our study. Out of the pharmacogenetic markers analyzed, MDR1 C3435T polymorphism had an influence on the overall survival.

Acknowledgments: The study was supported by the Science and Engineering Research Board (SERB) research grant (SB/FT/LS-147/2012).

Disclosures

No relevant conflicts of interest to declare.

Topics:
genotype, imatinib mesylate, leukemia, p-glycoprotein, accelerated phase, bcr-abl tyrosine kinase, chloroform, dna, genotype determination, phenol

Author notes

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Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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