Impacto pronóstico de la detección temprana de mutaciones en el dominio cinasa sobre la supervivencia de pacientes con leucemia mieloide crónica BCR-ABL positivo que reciben tratamiento con inhibidores de tirosina cinasa: revisión sistemática

Catalina Quintero Valencia; Liliana M.  Ochoa Galeano

doi:10.17533/udea.hm.5224

Authors

Catalina Quintero Valencia University of Antioquia
Liliana M. Ochoa Galeano University of Antioquia

DOI:

https://doi.org/10.17533/udea.hm.5224

Keywords:

BCR-ABL mutations, chronic myeloid leukemia, clinical evolution, mutational detection, prognosis, survival, treatment, tyrosine kinase inhibitors

Abstract

Introduction

The presence of BCR-ABL are important in mechanisms of resistance in CML, but the clinical benefits derived from its early detection, as a prognosis tool, have still not been demonstrated. This paper collects and systematically reviews data showing the effects of early detection of mutations on the survival of CML patients receiving treatment with tyrosine kinase inhibitors (TKI).

Materials and methods

We gathered randomized controlled clinical trials and corresponding data for the mutational analysis, which described the therapy phase when the analysis was done: pre-treatment, between zero and three months, or after the fourth month post-treatment with TKI. These studies provided data on the clinical phase, the overall survival, the progression-free survival and the response following for CML patients. The selected studies were published between 2001 and 2009. The search was done by two coworkers independently, using the Pubmed-Medline, Hinari and Science Direct databases. Both coworkers analyzed the information and chose trials that met the selection criteria, stored the trials using Endnote Web® software and analyzed them in a Microsoft Excel® matrix. The interesting results were described in terms of overall survival and progression-free survival index.

Results

Ten original articles were selected, which envolved trials including a total of 1.508 CML patients receiving first and second line TKI treatment (imatinib, dasatinib, nilotinib). The mutation type was considered a relevant factor, because the degree of resistance to treatment conferred varied among different mutation types, such as protein P-loop site and TKI binding site (T315I y F317L) mutations. We could not find any association between survival outcomes and the presence of mutations detected in the pre-treatment phase or in the first three months of therapy. We found contradictory results for the relation between the presence of late phase detected mutations and shortened survival. Additional data, such as mutation type detected, clinical phase, techniques used, patients’ classification and clonal selection, were found to have direct influence on the CML patient survival indices.

Discussion and Conclusions

The mutations’ impact on the survival of CMS patients is multifactorial. There is, therefore, a need for studies with appropriate methodology, in order to clearly demonstrate the utility of regular monitoring of mutations emerging during the first months of therapy, to allow following and management of the CML patients, and to justify the implementation of mutation monitoring in these patients.

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Author Biographies

Catalina Quintero Valencia, University of Antioquia

Microbiologist and Bioanalyst, University of Antioquia. Master's candidate in Microbiology and Bioanalysis, Emphasis in Hematology. Professor, Faculty of Medicine, University of Antioquia. Adult Hematology Laboratory University of Antioquia, San Vicente de Paul University Hospital.

Liliana M. Ochoa Galeano, University of Antioquia

Bacteriologist, Master in Basic Biomedical Sciences. Professor at the School of Microbiology, University of Antioquia. Adult Hematology Laboratory University of Antioquia, San Vicente de Paul University Hospital.

References

Organization WH. Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition ed. Fred T. Bosman ESJ, Sunil R. Lakhani, Hiroko Ohgaki, editor. Lyon, France: International Agency for Research on Cancer (IARC); 2008.

Pavon V. Leucemia mieloide crónica: actualización en citogenética y biología molecular. La Habana – Cuba; 2005.

Frame D. Chronic myeloid leukemia: standard treatment options. Am J Health Syst Pharm. 2006 Dec; 63(23 Suppl 8): S10-4; quiz S21-2.

Schiffer C. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med. 2007 Jul; 357(3): 258-65.

Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006 Sep; 108(6): 1809-20.

Aguilera D, Tsimberidou A. Dasatinib in chronic myeloid leukemia: a review. Ther Clin Risk Manag. 2009 Apr; 5(2): 281-9.

Melo J, Chuah C. Novel agents in CML therapy: tyrosine kinase inhibitors and beyond. Hematology Am Soc Hematol Educ Program. 2008: 427-35.

Melo J, Chuah C. Resistance to imatinib mesylate in chronic myeloid leukaemia. Cancer Lett. 2007 May; 249(2): 121-32.

Cang S, Liu D. P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia. J Hematol Oncol. 2008; 1: 15.

Baccarani M, Pane F, Saglio G. Monitoring treatment of chronic myeloid leukemia. Haematologica. 2008 Feb; 93(2): 161-9.

Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006 Jul; 108(1): 28-37.

Hehlmann R, Hochhaus A, Baccarani M. Chronic myeloid leukaemia. Lancet. 2007 Jul; 370(9584): 342-50.

Hernández-Boluda J, Cervantes F. Prognostic factors in chronic myeloid leukaemia. Best Pract Res Clin Haematol. 2009 Sep; 22(3): 343-53.

Pai M, McCulloch M, Gorman J, Pai N, Enanoria W, Ken-nedy G, et al. Systematic reviews and meta-analyses: an illustrated, step-by-step guide. Natl Med J India 17(2): 86-95.

O’Brien S, Berman E, Borghaei H, Deangelo D, Devetten M, Devine S, et al. NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. J Natl Compr Canc Netw. 2009 Oct; 7(9): 984-1023.

Khorashad J, de Lavallade H, Apperley J, Milojkovic D, Reid A, Bua M, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression. J Clin Oncol. 2008 Oct; 26(29): 4806-13.

Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood. 2003 Jul; 102(1): 276-83.

Willis S, Lange T, Demehri S, Otto S, Crossman L, Niederwieser D, et al. High-sensitivity detection of BCR-ABL kinase domain mutations in imatinib-naive patients: correlation with clonal cytogenetic evolution but not response to therapy. Blood. 2005 Sep; 106(6): 2128-37.

Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol. 2005 Jun; 23(18): 4100-9.

Nicolini F, Corm S, Lê Q, Sorel N, Hayette S, Bories D, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP). Leukemia. 2006 Jun; 20(6): 1061-6.

Jabbour E, Kantarjian H, Jones D, Talpaz M, Bekele N, O’Brien S, et al. Frequency and clinical significance of BCR-ABL mutations in patients with chronic myeloid leukemia treated with imatinib mesylate. Leukemia. 2006 Oct; 20(10): 1767-73.

Jabbour E, Kantarjian H, Jones D, Breeden M, Garcia-Manero G, O’Brien S, et al. Characteristics and outco-mes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy. Blood. 2008 Jul; 112(1): 53-5.

Jabbour E, Kantarjian H, Jones D, Reddy N, O’Brien S, Garcia-Manero G, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood. 2008 Dec; 112(13): 4839-42.

Jabbour E, Jones D, Kantarjian H, O’Brien S, Tam C, Koller C, et al. Long-term outcome of patients with chronic myeloid leukemia treated with second generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations. Blood. 2009; 112(13): 4839-4842.

Press R, Willis S, Laudadio J, Mauro M, Deininger M. Determining the rise in BCR-ABL RNA that optimally predicts a kinase domain mutation in patients with chronic myeloid leukemia on imatinib. Blood. 2009 Jul; 114(13): 2598-605.

Ernst T, Gruber F, Pelz-Ackermann O, Maier J, Pfirrmann M, Müller M, et al. A co-operative evaluation of different methods of detecting BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia on second-line dasatinib or nilotinib therapy after failure of imatinib. Haematologica. 2009 Sep; 94(9): 1227-35.

Bao F, Munker R, Lowery C, Martin S, Shi R, Veillon D, et al. Comparison of FISH and quantitative RT-PCR for the diagnosis and follow-up of BCR-ABL-positive leukemias. Mol Diagn Ther. 2007; 11(4): 239-45.

Soverini S, Colarossi S, Gnani A, Rosti G, Castagnetti F, Poerio A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res. 2006 Dec; 12(24): 7374-9.

Hughes T, Saglio G, Branford S, Soverini S, Kim D, Müller M, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol. 2009 Sep; 27(25): 4204-10.

Cortes J, Jabbour E, Kantarjian H, Yin C, Shan J, O’Brien S, et al. Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood. 2007 Dec; 110(12): 4005-11.

Soverini S, Gnani A, Colarossi S, Castagnetti F, Abruz-zese E, Paolini S, et al. Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood. 2009 Sep; 114(10): 2168-71.