Background: TP53 gene is a tumour suppressor gene located in the short arm of chromosome 17. TP53 plays a pivotal role in maintaining genomic stability in response to DNA damage. It is mutated in more than 50% of the human cancer. TP53 mutation (TP53mut) is commonly associated with therapy-related acute myeloid leukemia (AML) and complex karyotype. The incidence of TP53mutn was between 5-10% in de novo AML. This study described the clinicopathologic features of TP53mut AML and their clinical outcome in an Asian cohort.Method: 166 consecutively cell-banked marrow samples of AML were tested for TP53 mutations using a next generation sequencing platform. Baseline disease characteristic and clinical outcomes were retrospectively collected with approval granted by institutional review board.Results: 9/166 had TP53mut (5.4%). 6/9 of TP53mut AML was associated with complex karyotype (p<0.001). The remaining 3 cases were two acute promyelocytic leukemia (APML) and one with normal cytogenetics. TP53mut was mutually exclusive with FLT3 mutation. Two cases had concomitant NPM1 mutation and another two had ASXL1 mutation. TP53mut AML appeared to be associated with TET2 mutation (3/9, 33.3%) compared to 10.2% of the TP53wt (p=0.069). TP53mut AML had a lower CR rate compared to TP53wt (28.6% vs 84.3%, p=0.003). Only two cases achieved CR, one was an APML who remained in continuous remission after 4 years. The other case achieved CR after allogeneic transplant but, relapsed 8 months later. TP53mut AML was significantly associated with inferior OS compared to TP53wt (p=0.001). 0.8 months (95%CI: 0.159 -1.484) and 36.8 months (95%CI: 0.000 -92.676) respectively. It remains an independent predictor of OS in multivariate analysis that include cytogenetic risk, WBC, LDH and BM blasts (HR 43.07, 95%CI: 6.87-272.41, p<0.001). Conclusion:Our results confirmed the extremely dismal prognosis of TP53mut AML. TP53 mutation testing should be included as part of the pre-chemotherapy workout since this is not a standard practice as yet. The significance of its association with TET2 mutation requires further exploration in a larger study cohort.
Category: Basic Sciences/Biologics, Hindfoot, Sports Introduction/Purpose: Heel pain syndrome is a complex condition causing morbidity and decreases the quality of life in our adult population. It is known that individuals with a body mass index (BMI) of more than >30 kg/m2 have increased risk of plantar fasciitis. However, heel pain consists of larger entities not merely to plantar fasciitis alone. Limited study mentioned the association between hypertension and musculoskeletal pain. Platelet rich plasma (PRP) therapy is an emerging treatment option for its regenerative properties in the treatment of degenerative enthesopathic conditions as in plantar fasciitis and lateral elbow epicondylitis. We hypothesize that obesity (BMI>30 kg/m2) and hypertension do influence the poorer outcome after PRP injection in individuals with heel pain. Methods: We analysed 154 heel pain cases from orthopaedic outpatient clinic that were treated with PRP injection. BMI and BP were taken as preadmission measurements with at least three readings for blood pressure. PRP was harvested from the antecubital vein, and spun in a centrifuge machine. Follow-up was conducted with AOFAS Ankle Hindfoot system before injection, 6 weeks and up to 2 years after injection. Results: Mean age was 49.96 (range 20-81 years old) with 52.60% female and 47.4% male. Plantar fasciitis was the majority source of heel pain (71.43%) followed by achilles tendinopathy (26.62%), posterior tibial tendon disorder (1.3%), and peroneal tendinopathy (0.65%). One hundred and twenty-eight (83.1%) patients achieved resolution of heel pain and related symptoms after injection. Statistical analysis was performed using one sample student t-test. No statistical significant result was found in both overweight (p =0.29) and obesity grade 1 (p = 0.40). Statistical significant result found in the prehypertension group (p<0.04). Conclusion: Based on this preliminary data, we recommend weight loss with trials of lifestyle modification in individuals with obesity, and better control of our patients’ blood pressure in order to achieve comparable outcome with normal BMI population.
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