Dissertação
Monitoramento da resposta molecular aos inibidores de tirosino-quinase em pacientes com leucemia mieloide crônica
Fecha
2019-02-28Autor
Villa, Bárbara
Institución
Resumen
Chronic Myeloid Leukemia (CML) is associated with the chromosome Philadelphia. This abnormal
chromosome forms the chimeric BCR-ABL1 gene, which is responsible for producing a protein with
tyrosine kinase activity. Tyrosine kinase inhibitors drugs (ITKs) used in Brazil are imatinib mesylate (IM),
dasatinib and nilotinib. The response to these tests can be rated at three levels: hematological,
cytogenetic and molecular. This last one is more sensitive and evaluated with Reaction in Chain of Real
Time Polimerase (RQ-PCR). The treatment aims at achieving the Major Molecular Response (MMR),
whose ratio of bcr-abl1 chimeric transcript levels and endogenous control are less than or equal to 0.1%.
European Leukemia Net (ELN) establishes guidelines for molecular responses according to the
quantification of transcripts and the time of treatment with ITQs, classifying them as optimal response,
alert and failure. According to the literature, it is known that approximately 15-25% of patients treated
with MI do not reach optimal response. Due to the low number of studies that show how the molecular
monitoring of CML in Brazil is we decided to evaluate the molecular response to treatment with the ITQs
of CML patients treated in HUSM through RQ-PCR monitoring for quantification of transcripts of the
BCR-ABL1 fusion gene. The analysis was did through the database of the Hematology-Oncology
Service of the HUSM and the quantification of the transcripts and the mutation search in the ABL gene
were performed in an external laboratory. 117 medical records were reviewed, of which 58.11% were
male. The mean age at diagnosis was 48.1 years and 9.4% of the patients died. Six patients were
analyzed separately for different characteristics of the others. Thus, of the 111 patients, 52.25% of the
patients received exclusively MI, 42.30% reached MMR at 12 months and 73.40% had MMR at some
point during IM treatment. 54.25% of the patients who exclusively used IM reached the MMR and
maintained it to the end. Of the 47.74% that changed ITQ, 58.82% reached MMR shortly after the
exchange and maintained this response to the end. Of the 19 (37.25%) patients who failed during the
exchange, 14 went to the third line of therapy. Currently, 91.06% of patients who use IM are with MRM,
as are 65.37% of patients using nilotinib and 58.81% of those who use dasatinib. Of the patients who
were tested for mutation in the ABL gene, 40% had presence. According to the criteria of the EUROSKI
study, five patients would be eligible to enter a study protocol for Treatment-Free Referral. We
observed an improvement in monitoring over time, as well as good MMR results compared to the three
ITQs currently used in HUSM. Our results are in agreement with the literature and the HUSM has been