Clinical outcomes of patients with acute myeloid leukemia: evaluation of genetic and molecular findings in a real-life setting

Despite its undeniable importance, standard cytogenetic analysis is still not a routine practice for most reference centers in developing countries, and its accomplishment is practically limited to university research centers. Particularly in Brazil, little is known about the cytogenetic and molecular characterization of patients with acute myeloid leukemia (AML), and results about clinical outcomes remain scarce. In an effort to minimize the lack of results and contribute new insights in our setting, we reported clinical features and outcomes of 241 nonselectedBrazilian patientswithAML (nonacute promyelocytic leukemia) from 2 university hospitals, followed from November 2005 to April 2015. Patients were classified according morphologic, immunophenotypic, and cytogenetic findings. Treatment protocols were similar between centers. For patients up to 60 years of age, the treatment protocol was adapted according to performance status and the presence of comorbidities (in particular, cardiac disorders). Briefly, the conventional chemotherapy consisted of daunorubicin (45-90 mg/m per day for 3 days) and cytarabine (100-200mg/m per day for 7 days) or thioguanine, cytosine arabinoside, and daunorubicin as induction, followed by 3 or 4 cycles of consolidation therapy with high doses of cytarabine (.1 g/m per day). For patients who did not achieve complete remission (CR) after 1 course of chemotherapy, a second course was administered between days 28 and 35 after the end of the first course.CRwas assessed by bonemarrow examination on day 28 after each course of chemotherapy. For those who needed it, a postremission therapy based on autologous or allogeneic transplantation was performed. Patients older than 60 years were treated with low-dose cytarabine; a combination of etoposide, thioguanine, and idarubicin; or best supportive care. The local research ethics board of each participating center approved the study. Research was conducted in accordance with the Declaration of Helsinki. The baseline characteristics are summarized in supplemental Table 1. One hundred thirty patients were enrolled in Recife (northeast Brazil, 54%), and 111 patients were enrolled in Campinas (southeast Brazil, 46%). Baseline features were similar between centers. The median age was 47 years (range, 18-97 years) with 114 males (47%). Sixty-two patients (26%) were older than 60 years. Pretreatment bone marrow samples were analyzed by G-banding cytogenetics, of which 187 (78%) were successful. According to Medical Research Council trials, patients were stratified as follows: favorable (30/187, 16%), intermediate (119/187, 64%), and adverse (38/187, 20%). Overall, 101 patients (42%) were cytogenetically normal. To test whether the samples without cytogenetics results were missing at random, the overall survival (OS) was evaluated for patients with and without cytogenetics data. The 5-year OS rate did not differ between patients with (18%) and without (23%) available cytogenetics data (P 5 .372). Additionally, the entire cohort was fully characterized for NPM1 and FLT3-ITD mutations. Details can be found in the supplemental Data, available on the BloodWeb site. Out of 241 enrolled patients, 39 patients (16%) who started the induction treatment were lost to follow-up without assessment for CR. Of 202 evaluable patients, 115 (57%) achieved complete hematologic remission. CR rates according to the cytogenetic risk stratificationwere 33%, 64%, and 77% for adverse, intermediate, and favorable groups, respectively (P 5 .001). The logistic regression analysis revealed that age (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.93-0.98; P5 .002) and cytogenetic risk stratification (OR, 0.41; 95% CI, 0.19-0.89; P 5 .024) were independently