A higher percentage of leukemic blasts with vacuoles predicts unfavorable outcomes in patients with acute myeloid leukemia.

Cytoplasmic vacuoles, which are a morphological feature of dysplasia, can be observed under a microscope at initial diagnosis. Recently, this typical morphological feature has been found to be associated with impaired survival. To investigate the clinical significance of the grading of blasts with vacuoles in acute myeloid leukemia (AML), we retrospectively studied 152 patients newly diagnosed with non-M3 AML. The patients were categorized into three groups according to the percentage of blasts with vacuoles (>20 %, 11-20 %, 0-10 %). A high percentage of blasts with vacuoles (>20 %) was positively associated with the European Leukemia Net (2017-ELN) high-risk AML, a complex karyotype, TP53 and IDH1/2 mutations, and CD71 expression and negatively associated with the ELN low-risk category. Importantly, patients who had a higher percentage of blasts with vacuoles had a lower complete remission rate in response to first-cycle induction chemotherapy. The overall survival and event-free survival of patients who had a higher percentage of blasts with vacuoles were significantly shorter. Moreover, multivariate analysis showed that blast vacuolization was an independent high prognostic factor for AML. In conclusion, a higher percentage of leukemic blasts with vacuoles predicts worse outcomes in AML and may have potential as a prognostic marker.

Absolute Circulating Leukemic Cells as a Risk Factor for Early Bleeding Events in Patients with Non-High-Risk Acute Promyelocytic Leukemia.

BACKGROUND: Hemorrhagic complications are the most common cause of early death in patients with APL and remain a major challenge in the management of APL. Early fatal bleeding events occur not only in high-risk but also in non-high-risk acute promyelocytic leukemia (APL) patients with normal or low WBC counts. OBJECTIVES AND METHODS: To demonstrate the role of the absolute number of circulating leukemic cells in early bleeding events in APL patients. Clinical and laboratory characteristics of 149 patients newly diagnosed with APL were obtained from medical records and retrospectively investigated. RESULTS: In this study, circulating absolute leukemic cells were positively correlated with the WBC count (r=0.9813, p<0.001) in all patients with APL, and importantly, they were strongly associated with significant bleeding events in non-high-risk patients. Multivariate logistic regression analysis showed that the absolute number of leukemia cells was an independent risk factor for significant bleeding events in APL patients. A cut-off value of 2.59×109/L for circulating leukemic cells to predict significant bleeding events in APL patients was obtained by ROC curve analysis. We further confirmed that the significant bleeding rate of patients with non-high-risk APL was statistically increased when the absolute number of circulating leukemic cells was ≥2.59×109/L. CONCLUSION: Circulating leukemic cell content has great clinical value for predicting early bleeding events in APL patients, especially in non-high-risk APL.

The relationship between leukemia and TP53 gene codon Arg72Pro polymorphism: analysis in a multi-ethnic population.

Aim: Many studies have analyzed the relationship between Arg72Pro polymorphism of TP53 and leukemia; nevertheless, the findings continue to be indeterminate. We, therefore, performed an updated meta-analysis in multi-ethnic groups using specialized software for genome-wide association studies meta-analysis. Materials & methods: PubMed, EMBASE and Google Scholar were searched up to October 2018. An odds ratio (OR) with the corresponding 95% CI was used to evaluate the strength in the association. Results: This meta-analysis included 16 studies with 2337 cases and 9494 controls. In the overall population, significant relationship between Arg72Pro polymorphism of TP53 and leukemia susceptibility was found in two genetic models (recessive model: OR = 1.276, 95% CI = 1.102-1.476; p = 0.01; overdominant model: OR = 0.891, 95% CI = 0.802-0.988; p = 0.03). In stratified studies with ethnicity, a significant association was found in five ethnic groups, including Chinese, Americans, Africans, Japanese and Indians. Conclusion: We demonstrated that an association exist between leukemia risk and TP53 gene codon Arg72Pro polymorphism in the recessive and overdominant genetic models. Also, our findings show that the TP53 Arg72Pro polymorphism may influence leukemia development in different populations.

Evaluating and monitoring bone marrow hypoplasia in adults with aplastic anemia via high-resolution iliac magnetic resonance imaging in the current era.

The diagnosis and monitoring of aplastic anemia (AA) rely heavily on a complete blood count (CBC), and multiple-site bone marrow (BM) aspirations and biopsies. However, these approaches have certain limitations. We aimed to assess high-resolution magnetic resonance imaging (MRI) as a complementary approach for evaluating BM hypoplasia and monitoring treatment response in adults with AA in the current era.Twelve newly diagnosed AA patients and 12 sex- and age-matched healthy controls were enrolled in this study from January 2017 to August 2018. A bilateral iliac 3.0T MRI was used to collect data for each subject, and the signal intensity on the T1-weighted images (T1WIs) were expressed as a contrast-to-noise ratio (CNR). The MRI, CBC, and BM biopsy data were analyzed and compared.A qualitative analysis identified a significant difference in MRI signal characteristics between the AA group and the healthy control group. The clinical classifications of very severe aplastic anemia (VSAA) and severe aplastic anemia (SAA) corresponded to pattern I and pattern II on the MR images, respectively. However, this imaging classification did not correlate with the biopsy-based BM cellularity measure. A quantitative analysis showed a significantly higher signal intensity in AA patients than in controls. A within-group comparison revealed that more severe types of AA, based on the clinical classification, corresponded to stronger signals. Notably, MRI could detect treatment response earlier than CBC, regardless of whether there were improvements in hematopoiesis.MRI can be used to predict the therapeutic effects in patients with AA and is an important complementary tool for evaluating and monitoring BM hypoplasia.