Mixed phenotype acute leukemia (MPAL) in adults represents nearly 2 to 5 % of all acute leukemia cases. There are two large studies throughout the world and only case reports and small series have been reported in Latin America. This study retrospectively analyses the clinical characteristics and survival of 27 patients with MPAL evaluated in three medical institutions of Mexico. All cases meet World Health Organization 2008 criteria; 70.3 % of patients had B lymphoid/myeloid lineage MPAL. Induction chemotherapy protocols included 7 + 3 hyper-CVAD, high-density schedules, and pediatric-like regimens such as New York II and total XI. Complete remission was achieved in 23/27 patients (85.2 %). Only one patient died due to chemotherapy-induced aplasia during remission induction (5.2 %). In 68 % of cases, we were able to administer maintenance therapy as a regimen in lymphoblastic leukemia. At the time of analysis, 70.4 % of the patients in the entire cohort had died mainly as result of disease progression (73.6 %). Disease-free survival was 13 months (95 % CI, 9.6-16.3 months) and overall survival was 14.8 months (95 % CI 13.4-16.27). Survival rates are low and standardized therapy for the management of this type of leukemia is still lacking. This is the largest series reported in Mexico and to the best of our knowledge in Latin America.

Chronic myeloid leukemia (CML) is one of the most frequent hematological neoplasia worldwide. The abnormal accumulation of reactive oxygen species may be an important factor in CML development. The transcription factor NRF2 can regulate the transcription of a battery of antioxidant and detoxificant genes after heterodimerizing with small-Maf proteins. Although the participation of NRF2 in the development of chronic degenerative diseases has been thoroughly studied, the role of small-Maf genes has not been documented. We have identified polymorphisms in the three MAF genes (F, G and K) and assessed their association with CML. Over 266 subjects with CML and 399 unrelated healthy donors have been studied. After sequencing each MAF gene by Sanger technology, we found 17 variants in MAFF gene, eight in MAFG and seven in MAFK. In the case-control study, the homozygote genotype CC for the rs9610915 SNP of MAFF was significantly associated with CML. The frequency of the ACC haplotype from MAFK was significantly lower than controls. After stratification by gender, the ACC and GTG haplotypes were associated only with males with CML. These novel data suggest an association between MAFF and MAFG and the development of CML.

Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.

Background: Myelodysplastic syndrome (MDS) is associated with persistent immune activation. High mobility group box-1 (HMGB1) is a ubiquitous, functionally diverse, non-histone intranuclear protein. During acute and chronic inflammatory states, HMGB1 is actively released by inflammatory cells, further amplifying the inflammatory response. A role in MDS and other hypoplastic bone marrow (BM) disorders is incompletely understood. Objectives: The objective of the study is to evaluate whether circulating HMGB1 is elevated in patients with MDS and other BM failure syndromes [namely, aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH)]. Design: This is a observational, cross-sectional, single-center, exploratory study. Methods: We evaluated circulating concentrations of HMGB1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in patients with MDS and age-matched hematologically healthy controls as well as patients with AA and PNH. Results: We included 66 patients with MDS and 65 age-matched controls as well as 44 patients with other BM failures (AA = 27, PNH = 17). Circulating levels of HMGB1 were higher in patients with MDS [median, 4.9 ng/ml; interquartile range (IQR): 2.3–8.1] than in AA (median, 2.6 ng/ml; IQR: 1.7–3.7), PNH (median, 1.7 ng/ml; IQR: 0.9–2.5), and age-matched healthy individuals (median, 1.9 ng/ml; IQR: 0.9–2.5) ( p = 0.0001). We observed higher concentrations of HMGB1 in the very low/low-risk MDS patients than in the intermediate/high/very high-risk ones ( p = 0.046). Finally, in comparison with patients with AA, those with hypocellular MDS (h-MDS) had significantly higher levels of circulating HMGB1 ( n = 14; median concentration, 5.6 ng/ml, IQR: 2.8–7.3; p = 0.006). We determined a circulating HMGB1 value of 4.095 ng/ml as a diagnostic cutoff differentiator between h-MDS and AA. Conclusion: These observations indicate that circulating HMGB1 is increased in patients with MDS. HMGB1 (but not IL-1β or TNF-α) differentiated between MDS and other BM failures, suggesting that HMGB1 may be mechanistically involved in MDS and a druggable target to decrease inflammation in MDS.

A cross-sectional pilot study was conducted in acute leukemia adult patients in order to characterize oral mucosal conditions in acute leukemia, and to analyze their association with certain clinical, nutritional and laboratory parameters. Oral evaluation was performed. Epidemiologic, clinical and laboratory data were considered. Statistical analysis included non-parametric tests and multivariate analysis. A total of 30 patients (60% males) were included; median age of 39 (range 17-62) years old. The median percentage of caloric intake adequacy was 96.8% (range 21.8-205.7%), and the median ideal weight was 117.9% (range 88.2-162.9%). The most common oral mucosal findings were pallor and furred tongue. Leukoedema was seen only in patients <30 years old [OR=1.9 (CI=1.1-3.1); p=0.003]; more cases of fissured tongue [OR=17.1 (CI=1.8-163.8); p=0.005] were seen in subjects >30 years old. Exfoliative cheilitis was more frequent in females [OR=2.7 (CI=1.2-6.1); p=0.02] and in patients with high β-carotene concentrations [Md= 94.5 vs 57.0 µg/dl; (p=0.01)]. Higher rates of diffuse hyperpigmentation were seen (p<0.05) in patients having low vitamin B12 [Me=240 vs 626 pg/ml] and folic acid concentrations [Md=5.8 vs 8.5 ng/ml]; Geographic tongue was found among patients with low serum albumin [Md= 2.7 vs 3.5 g/dl; (p=0.006)] and folic acid [Md=7.9 vs 11.6 ng/mL; (p=0.02)]. Furred tongue was more frequent in patients with low hemoglobin concentration [Md=7.2 vs 8.5 g/dl ;( p=0.01)] and poor oral hygiene [Md=1.1vs 0.7 ;( p=0.04)]. Nutritional depletion was more frequently observed among patients with indentation (p=0.04) and geographic tongue (p=0.03)]. Age, gender and certain micronutrient deficiencies were significantly associated to specific oral mucosal findings in acute leukemia.