Leucemia Mieloide Crônica: histórico, tratamento com inibidores de tirosino-quinase e recomendações da Leukemia NetOs primeiros casos de leucemia mieloide crônica (LMC) foram descritos em 1845. Em 1960 foi descrito o cromossomo Filadélfia (Ph), depois identificado como uma translocação recíproca entre os cromossomos 9 e 22. Em 1983, demonstrou-se que esta translocação justapõe a região BCR no cromossomo 22, ao gene c-ABL localizado no cromossomo 9, resultando num gene híbrido -o BCR-ABL. Em seguida verificou-se que o produto deste oncogene era uma proteína de 210 KD, com atividade de tirosina quinase. Em 1990, foi demonstrado em um modelo murino, que a presença do gene híbrido induzia uma doença mieloproliferativa semelhante à LMC vista em humanos, estabelecendo relação de causalidade entre o BCR-ABL e a LMC. 1,2 A irradiação corporal total ou esplênica, o uso de derivados de arsênico (licor de Fowley), o bussulfano e a hidroxiureia, tratamentos utilizados inicialmente, resultavam em controle hematológico, mas não havia mudança da histó-ria natural da doença, com uma inexorável progressão para

INTRODUCTION: CML relapsed after HSCT has been treated with donor lymphocyte infusions (DLI), with responses achieving 60–70%, and even better results in earlier relapses. However, complications as chronic GVHD and myelossupression can be a problem, especially on those who receive larger DLI doses. The present study has the objective of evaluate quality of response and chimerism in patients who received Gleevec as therapy for relapsed CML after HSCT. PATIENTS AND METHODS: We report 32 CML patients who received Gleevec as therapy for relapse after HSCT. Age: 13 – 56 (Median: 38 y); sex M/F: 17/15; Allogeneic HSCT: 31 pts, syngeneic: 1 pt. Time from HSCT to relapse: 0–122 m (M 16m). Relapse was hematologic in 29 and cytogenetic in 3 patients. Phase at hematologic relapse: CP-14 pts, AP-11 pts and BC-4 pts; clonal evolution: 7 patients. Previous VNTR was available in 16 pts: 10–35% donor in 11, 0% donor in 3 and 95% donor in 2 pts. Previous DLI: 14 pts. Dose: 600mg QD in 15 pts, 400 mg QD - 17 pts. RESULTS: Therapy duration: 7–1795 d (M 365 d). 27 (84%) pts reached complete hematologic response (CHR). Time to CHR: 7–60 d (M 28 d). Cytogenetic response was available for 25 pts, being complete in 16 (48%), partial in 2 and absent in 7 pts. Competitive Q-PCR was available in 21 patients, of whom 10 had major molecular responses (3-log reduction at the BCR-ABL/ABL ratio). In 6 (18%) patients, BCR-ABL was negative by nested PCR. Four (13%) pts relapsed after a initial response (1 BC, 3 AP). Nine from 10 pts with sequential VNTR, improved chimerism to more than 95% donor cells after Gleevec therapy. One patient had autologous recovery of Ph negative cells. Hematologic toxicity grade II–IV was observed in 21 pts (63%). Eleven pts developed grade IV neutropenia with a duration of 0–8m (M 2m). Five pts developed non-hematologic toxicity grade III–IV. Dose was held in 4 pts, increased in 6 and reduced in 11 pts. Only two pts developed skin and liver chronic GVHD, and two patients who had c-GVHD before therapy with imatinib did not flare. Estimated 5y OS is 67%. CONCLUSIONS:Gleevec can be used safely as therapy for BMT relapse, with durable cytogenetic and molecular responses in chronic phase;Complete chimerism is often reestablished by Gleevec therapy after allogeneic BMT;Increased incidence of GVHD was not observed in this group of patients.