Encouraging results with the compassionate use of hydralazine/valproate (TRANSKRIP™) as epigenetic treatment for myelodysplastic syndrome (MDS).

The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day. Both drugs were given daily until disease progression. Response and toxicity were evaluated with the International Working Group criteria and CTCAE, version 4, respectively. Survival parameters were estimated with the Kaplan-Meier method. From 2009 to 2012, 14 patients were treated. The median age ± SD was 55.2 ± 19.52 (range 23-87) years. According to the IPSS, cases were graded as intermediate-1 (n = 8/14; 57.2%) or intermediate-2 (n = 6/14; 42.8%). Responses were as follows: five (35.7%) complete response, one (7.1%) partial response, and two (14.28%) became transfusion independent. The mean duration of response ± SD was 60 ± 35.28 months (range 5-94). Three patients progressed to AML. At a median follow-up of 57 months (range 1-106), the median OS was 27 months. At that point, five patients remained on the treatment, one with partial response and four with complete response. The median OS was not reached in the eight patients who saw a clinical benefit from the treatment, in comparison to an OS of 7 months in the six patients who had no treatment. The combination of hydralazine and valproate is safe and effective in MDS, and its further testing is highly desirable.

Acute Myeloid Leukemia in Mexico: The Specific Challenges of a Developing Country. Results From a Multicenter National Registry.

BACKGROUND: In the past decades, long-term survival outcomes for younger patients with acute myeloid leukemia (AML) have improved. Nonetheless, developing nations might be lagging behind, highlighting the need to assess real-world outcomes in such regions. METHODS: We performed a multicenter retrospective study, which included patients with AML diagnosed between January 2013 and December 2017 from 13 centers in Mexico. RESULTS: A total of 525 patients with AML met the inclusion criteria and were included in the study. Median age for the entire cohort was 47 years. The patients were classified according to cytogenetic risk: favorable 16.0%, intermediate 55.6%, and unfavorable 28.4%. Most patients received intensive chemotherapy (80.2%), and among these 74.1% underwent a 7 + 3 induction regimen. A complete remission was achieved in 71.3% of patients. Induction-related mortality occurred in 17.8% and we identify the following as independent risk factors: >60 years (odds ratio [OR] 2.09 [1.09-4.02]), Eastern Cooperative Oncology Group >2 (OR 4.82 [2.46-9.43]), prior solid tumor (OR 3.8 [1.24-11.59]) and active infection (OR 1.82 [1.06-3.12]). Further, allogeneic hematopoietic stem-cell transplantation (AlloHSCT) was performed in 8.2% in CR1. The 3-year overall survival (OS) was 34.8%. In a multivariate analysis, several factors were independently associated with a worse OS, including secondary AML (hazard ratio [HR] 2.14 [1.15-4.01]) and unfavorable cytogenetic risk (HR 1.81 [1.16-2.82]), whereas maintenance therapy (HR 0.53 [0.32-0.86]) and AlloHSCT (HR 0.40 [0.17-0.94]) were associated with better OS. CONCLUSIONS: This is the first multicenter report analyzing AML survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed to improve outcomes.