RESUMO
Imatinib mesylate (IM) is now first-line treatment for CML. To study the results of treatment with IM after IFN failure/intolerance versus allogeneic BMT (allo-BMT), we retrospectively analyzed 264 patients treated for CML in first chronic phase in three different institutions. Over a 6-year period (2001-2006), 174 patients received IM after failure of or intolerance to IFN. During the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). The IM group was older (41 versus 33 years, P<0.001). Five-year EFS was 62% among patients receiving IM and 52% among patients undergoing allo-BMT (P=0.0002). OS at 5 years was 93% for IM-treated patients and 59% for patients undergoing allo-BMT (P<0.0001). Allo-BMT cannot be considered as first-line treatment for CML patients in first chronic phase.
Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/terapia , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Benzamidas , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Mesilato de Imatinib , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Adulto JovemRESUMO
Point mutations in codons 12, 13 and 61 of the N-ras proto-oncogene have been detected in several human malignancies. We studied 170 patients with acute lymphoblastic leukemia (ALL), treated from 1988 to 1994 according to a protocol derived from BFM-83 studies, in order to evaluate the incidence and prognostic significance of mutations in this gene in childhood ALL. DNA was extracted from bone marrow smears at diagnosis and amplified by polymerase chain reaction (PCR). After screening with SSCP, PCR products were hybridized with allele specific probes and, in some cases, cloned in a pMOS Blue T vector and sequenced. Exon 2 was also studied in 101 children. Our results showed 4% of mutations in codons 12 and 13 and 2% in exon 2. Similar to a previous report, we identified 7% of mutations among children who were studied for both exons. A new mutation in codon 64 of the N-ras gene was detected in one patient. No significant clinical differences between patients with and without mutations were detected (sex, age, leukocyte counts at diagnosis, nutritional status, and risk factor according to the BFM protocol). Children with mutations in codons 12 and 13 showed significantly higher reactivity to PAS staining on blast cells than children with a wild type N-ras gene configuration. Comparison of overall- and recurrence-free survival did not show significant difference between groups with and without mutations. Our results suggest that mutations in the ras gene are infrequent in children with ALL at diagnosis and seem to be of low prognostic value.