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Results of treatment of acute lymphoblastic leukemia in two cohorts of Mexican patients (Rev Med Chile 2011; 139: 1135-1142.

ObjectiveApproximately 40–50% of patients with acute myeloid leukaemia (AML) have been reported to present with a normal karyotype and a variable disease-free period, most likely due to the molecular heterogeneity presented by these patients. A variety of mutations have been identified at the molecular level, such as those in the IDH1/2 gene, which causes a gain of function of the isocitrate dehydrogenase enzyme, generating high levels of the (R)-2-hydroxyglutarate oncometabolite, which competitively inhibits dioxygenase enzymes. Therefore, the objective of this study was to evaluate the incidence of IDH1/2 gene mutations in AML patients and their impact on survival.Materials and methodsA total of 101 patients with a diagnosis of AML were included; mononuclear cells were obtained for DNA extraction and purification. Mutations were detected using TaqMan™ competitive allele-specific probes (castPCR™). Overall survival curves were plotted using IBM SPSS Statistics 23 software.ResultsThe frequency of IDH gene mutations was 19.8%. For the IDH1 gene, 13.8% of the mutations identified included R132H, V178I, G105G and R132C. The frequency of mutations of the IDH2 gene was 5.9%; the variants included R172K and R140Q. The mean survival time in patients without IDH1 gene mutations was 173.15 days (120.20–226.10), while the mean survival time for patients with mutations was 54.95 days (9.7–100.18), p = 0.001.ConclusionThe frequency of IDH1 and IDH2 gene mutations in the sample was similar to that reported in other studies. The analysis of these mutations in AML patients is of great importance as a prognostic factor due to their impact on survival and their use as potential therapeutic targets or as targets of inhibitors of IDH1(Ivosidenib, Tibsovo) and IDH2 (Enasidenib, Idhifa).

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Background:In the last decades, the outcome of patients with AML treated with intensive chemotherapy have improved, reaching long‐term overall survival (OS) >40%. This has been due to better supportive care and risk stratification with cytogenetic/molecular tests, increasingly access to transplant (HSCT) programs and more recently, new drugs. This improvement has not been equivalent in developing countries were the OS is lower. There are no multicentric studies with survival analysis in Mexico.Aims:To analyze the outcome of Mexican adult patients with AML treated with intensive chemotherapy.Methods:Multicentric and retrospective study, including patients with AML diagnosed between January 2013 and December 2017 in 13 centers in Mexico.Results:The information of 525 patients with AML with a median age of 47 years was recorded. Cytogenetics were available in 363/525 patients (69.1%). The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6% and unfavorable 28.4%. FLT3 mutations were analyzed in 64 cases and positive in 22% and NPM1 mutations in 43 cases and positive in 12%. Other mutations were analyzed less frequently. The majority of the patients (80.2%) were treated with intensive chemotherapy. When comparing them with those receiving non‐intensive regimens, they were younger (43 vs. 70 years, p < 0.001), with less comorbidity (HCT‐CI≥ 3 11.2% vs. 32.7%, p < 0.001) and fewer secondary AML (10.5% vs. 26.9%, p < 0.001). The most common induction regimen was 7+3 in 74.1%. The complete remission (CR) rate was 71.3%. Induction related mortality occurred in 17.8% and we identify as independent risk factors: >60 years (OR=2.088), ECOG>2 (OR=4.820), prior solid tumor (OR=3.795) and active infection (OR=1.817). Some patients (28.9%) received maintenance therapy after consolidation: methotrexate and 6‐mercaptopurine (66.3%), cytarabine‐based (27.7%) or hypometilating agents (6%). Allogeneic HSCT was performed in 33 patients (8.2%) in first CR.The 3‐year overall survival (OS) was 34.8% (median OS of 13.9 months). Cytogenetic risk was significantly associated with survival, with median OS of 45.2, 20.5 and 12 months for favorable, intermediate and unfavorable cytogenetics (p = 0.001). Survival increased in patients with less comorbidities (16.6 vs. 8 months, p = 0.001) and in those who received allogenic HSCT in first remission (median NR vs. 10.6 months, p < 0.01). Interestingly, during remission, any maintenance therapy had a positive trend in survival compared to those with no maintenance: median NR vs. 27.1 months, p = 0.011; nevertheless, this advantage was only significant for patients receiving cytarabine‐based maintenance (p = 0.021) and for intermediate cytogenetic risk (p = 0.017). In a multivariate analysis, prognostic factors related to worse OS were secondary AML (HR=2.029) and high cytogenetic risk (HR=1.874), whereas maintenance therapy (HR=0.547) and allogeneic HSCT (HR=0.034) were associated with better OS.Summary/Conclusion:This is the first large multicentric report that analyses the outcome of adult AML patients in Mexico. The impact of cytogenetic risk on survival was like previous reports. The use of a cytarabine‐based maintenance is associated with better survival only in intermediate‐risk patients. We identified some short‐term challenges: to standardize supportive care in order to reduce induction‐related mortality and to expand access to cytogenetic/molecular testing and HSCT programs. This will be addressed in a prospective multicentric trial.image