ABSTRACT
INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML) in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR) rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil). BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60% probability of achieving MMR, while the probability for those patients who received late treatment was 40%. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79%), compared with patients who received early treatment (21%, odds ratio=5.75, P=0.012). The probability of maintaining MMR at 30 months of treatment was 80% in the early treatment group and 44% in the late treatment group (P=0.0005). CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Benzamides , Female , Fusion Proteins, bcr-abl/metabolism , Humans , Imatinib Mesylate , Kaplan-Meier Estimate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Male , Middle Aged , Remission Induction , Time Factors , Treatment Outcome , Young AdultABSTRACT
INTRODUCTION: In Brazil, patients with chronic myeloid leukemia (CML) in the chronic phase were not given first-line imatinib treatment until 2008. Therefore, there was a long period of time between diagnosis and the initiation of imatinib therapy for many patients. This study aims to compare the major molecular remission (MMR) rates of early versus late imatinib therapy in chronic phase CML patients. METHODS: Between May 2002 and November 2007, 44 patients with chronic phase CML were treated with second-line imatinib therapy at the Hematology Unit of the Ophir Loyola Hospital (Belém, Pará, Brazil). BCR-ABL transcript levels were measured at approximately six-month intervals using quantitative polymerase chain reaction. RESULTS: The early treatment group presented a 60 percent probability of achieving MMR, while the probability for those patients who received late treatment was 40 percent. The probability of either not achieving MMR within one year of the initiation of imatinib therapy or losing MMR was higher in patients who received late treatment (79 percent), compared with patients who received early treatment (21 percent, odds ratio=5.75, P=0.012). The probability of maintaining MMR at 30 months of treatment was 80 percent in the early treatment group and 44 percent in the late treatment group (P=0.0005). CONCLUSIONS: For CML patients in the chronic phase who were treated with second-line imatinib therapy, the probability of achieving and maintaining MMR was higher in patients who received early treatment compared with those patients for whom the time interval between diagnosis and initiation of imatinib therapy was longer than one year.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Fusion Proteins, bcr-abl/metabolism , Kaplan-Meier Estimate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Remission Induction , Time Factors , Treatment Outcome , Young AdultABSTRACT
Chronic myeloid leukemia (CML) originates from the hematopoietic stem cell and is characterized by the reciprocal translocation t(9;22)(q34;q11), which results in the BCR-ABL fusion gene on chromosome 22q-, also known as the Philadelphia chromosome. This chimeric gene codes for a cytoplasmic protein with constitutive tyrosine-kinase activity, responsible for cellular transformation and leukemogenesis in CML. The aim of this observational cohort study was to discriminate and quantify BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis). Twenty-two patients were followed for six months during treatment. Quantitative real time polymerase chain reaction was performed before treatment and after 3 and 6 months from treatment initiation. As compared with the third month, there was a significant decrease in BCR-ABL expression in the sixth month of treatment (P = 0.0002). At the sixth month, there was a significant difference in the levels of the two major transcripts of BCR-ABL, B2A2 and B3A2 (P = 0.0347), indicating that B2A2 may be more sensitive to imatinib. The results of our study indicate that imatinib is able to modify the natural history of CML, and raise the hypothesis that patients who express the B2A2 transcript may have a better prognosis.
