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Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

ABSTRACT: Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ?88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-? only (n=3). The most common malignancies (n?4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.

SUBMITTER: Miranda MB

PROVIDER: S-EPMC4895174 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

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Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

Miranda M B MB Lauseker M M Kraus M-P MP Proetel U U Hanfstein B B Fabarius A A Baerlocher G M GM Heim D D Hossfeld D K DK Kolb H-J HJ Krause S W SW Nerl C C Brümmendorf T H TH Verbeek W W Fauser A A AA Prümmer O O Neben K K Hess U U Mahlberg R R Plöger C C Flasshove M M Rendenbach B B Hofmann W-K WK Müller M C MC Pfirrmann M M Hochhaus A A Hasford J J Hehlmann R R Saußele S S

Leukemia 20160209 6

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) ...[more]

PMID: 26859076

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Project description:OBJECTIVE:Cytochrome P450 is one of the major drug metabolizing enzyme families and its role in metabolism of cancer drugs cannot be less emphasized. The association be- tween single nucleotide polymorphisms (SNPs) in CYP1A1 and pathogenesis of chronic myeloid leukemia (CML) has been investigated in several studies, but the results observed vary based on varied risk factors. The objective of this study was to investigate the risk factors associated with the CYP1A1*2C [rs1048943: A>G] polymorphism in CML patients and its role in therapeutic response to imatinib mesylate (IM) affecting clinico-pathological parameters, in the Indian population. MATERIALS AND METHODS:In this case-control study, CYP1A1*2C was analysed in CML patients. After obtaining approval from the Ethics Committee of oncology hospital, we collected blood samples from 132 CML patients and 140 matched controls. Genom- ic DNA was extracted and all the samples were analysed for the presence of the CYP1A1*2C polymorphism using allele-specific polymerase chain reaction, and we examined the relationship of genotypes with risk factors such as gender, age, phase of the disease and other clinical parameters. RESULTS:We observed a significant difference in the frequency distribution of CYP1A1*2C genotypes AA (38 vs. 16%, P=0.0001), AG (57 vs. 78%, P=0.0002) and GG (5 vs. 6%, P=0.6635) between patients and controls. In terms of response to IM therapy, significant variation was observed in the frequencies of AA vs AG in major (33 vs 67%) and poor (62 vs 31%) hematological responders, and AA vs AG in major (34 vs. 65%) and poor (78 vs. 22%) cytogenetic responders. However, the patients with the GG homozygous genotype did not show any significant therapeutic outcome. CONCLUSION:The higher frequency of AG in controls indicates that AG may play a protec- tive role against developing CML. We also found that patients with the AG genotype showed favorable treatment response towards imatinib therapy, indicating that this polymorphism could serve as a good therapeutic marker in predicting response to such therapy.

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Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

Publications

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

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