Chronic myeloid leukemia treatment guidelines: Brazilian Association of Hematology, Hemotherapy and Cell Therapy. Brazilian Medical Association Guidelines Project – 2012 Recommendation: The monitoring of CML patients treated with TKIs can be accomplished by bone marrow cytogenetics and qPCR for the BCR-ABL gene in peripheral blood, thereby allowing an estimation of prognosis and the definition of therapeutic strategies. Mutational analysis should be performed in patients with suboptimal response or loss of response to TKIs. When should bone marrow indicated for CML patients? transplantation be Imatinib may be used as treatment for relapse after allogeneic hematopoietic stem cell transplantation, the prevalence of which ranges from 40% to 70% at 5 months. In the chronic phase, the cytogenetic and hematologic response rates obtained and survival at 9 months are 58%, 84% and 100%, respectively(93,94) (B). Imatinib came to be used as first-line treatment in the chronic phase of CML demonstrating increased survival when used before bone marrow transplant(95)(B). Due to the lower cost, resistance to imatinib or advanced stages of the disease (accelerated and blast crisis phases), some series of cases of transplant in CML have been reported with comparative results or in association to imatinib, demonstrating similar disease- free survival, overall survival and cardiotoxicity(96)(C). The previous use (before transplantation) of imatinib in patients with advanced stages of CML, produces hematological response in 73% and cytogenetic response in 40% of patients, and 3 years after the transplant, 66.7% of patients have complete molecular response(97)(C). In a prospective study, Jiang et al. compared accelerated phase patients treated either with imatinib (n = 87) or allogeneic transplantations (n = 54). In this study, multivariate analysis established hemoglobin < 10.0 g/dL, blasts in peripheral blood ≤ 5% and disease duration of less than 12 months as independent risk factors for survival. High-risk (two risk factors or more) or intermediate-risk patients (one risk factor) had better overall survival and progression-free survival with allogeneic transplant. No difference was seen with low-risk patients(98)(BII). The mortality of CML patients on imatinib treatment associated to hematopoietic stem cell transplant is 9.7% and the relapse rate is 5.0% at one year(99)(C). Despite the new options in imatinib-resistant patients, such as dasatinib and nilotinib, non-comparative case series that associate TKIs and transplant are still being performed(100)(C). Data are still limited for the pediatric population, but the results with imatinib are similar to those seen in adults. Millot et al. published their experience in 44 children with newly diagnosed CML treated with imatinib. With a median follow- up of 31 months, the estimated progression-free survival at 36 months was 98%. The rates of complete cytogenetic response and major molecular response at 12 months were 61% and 31%, respectively. About 30% of the children discontinued the use of medication, mainly due to lack of effectiveness. There are adverse effects of TKIs on the growth of children and this aspect should be monitored(101)(BII). Rev Bras Hematol Hemoter. 2012;34(5):367-82 Moreover, researchers reported the results of a prospective study involving 200 CML children and adolescents treated by allogeneic transplantation according to donor availability. The probability of survival at five years was 87 ± 11% for matched related donors, 52 ± 9% for matched unrelated donors and 45 ± 16% for unmatched donors. The likelihood of relapse at 5 years was 20 ± 12%(102)(BII). Recommendation: Bone marrow transplantation is a therapeutic option to treat CML but it should be reserved for cases resistant to TKI treatment and patients in the advanced stages of the disease after an initial course of TKIs. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Baccarani M, Dreyling M; ESMO Guidelines Working Group. Chronic myelogenous leukemia: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009;20(Suppl 4):105-7. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51. Comment in: Blood. 2010;115(3):748-9; author reply 749-50. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008;22(1):14-22. Comment in: Leukemia. 2008;22(11):2118-9. Verma D, Kantarjian HM, Jones D, Luthra R, Borthakur G, Verstovsek S, et al. Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance. Blood. 2009;114(11):2232-5. Lucas CM, Harris RJ, Giannoudis A, Davies A, Knight K, Watmough SJ, et al. Chronic myeloid leukemia patients with the e13a2 BCR-ABL fusion transcript have inferior responses to imatinib compared to patients with the e14a2 transcript. Haematologica. 2009;94(10):1362-7. Comment in: Haematologica. 2010;95(5):852-3. de Lemos JA, de Oliveira CM, Scerni AC, Bentes AQ, Beltrão AC, Bentes IR, et al. Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia. Genet Mol Res. 2005;4(4):803-11. Sharma P, Kumar L, Mohanty S, Kochupillai V. Response to Imatinib mesylate in chronic myeloid leukemia patients with variant BCR-ABL fusion transcripts. Ann Hematol. 2010;89(3):241-7. Kreil S, Pfirrmann M, Haferlach C, Waghorn K, Chase A, Hehlmann R, Reiter A, Hochhaus A, Cross NC; German Chronic Myelogenous Leukemia (CML) Study Group. Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic myelogenous leukemia. Blood. 2007;110(4):1283-90. Ghaith F, Abdou S, El-Bendary A, Shahin D, Eid M, Megeed WA, et al. Prognostic relevance of 9q34 deletion and the suppressor of cytokine signalling-1 in CML patients. Int J Lab Hematol. 2010;32(1 Pt 2):103-12. 10. Cohen N, Rozenfeld-Granot G, Hardan I, Brok-Simoni F, Amariglio N, Rechavi G, et al. Subgroup of patients with Philadelphia-positive chronic myelogenous leukemia characterized by a deletion of 9q proximal to ABL gene: expression profiling, resistance to interferon therapy, and poor prognosis. Cancer Genet Cytogenet. 2001;128:114-9. 11. Quintas-Cardama A, Kantarjian H, Talpaz M, O’Brien S, Garcia-Manero 375