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Additional file 2: Supplementary tables.

Additional file 1: Appendix.

Background specific heart rate parameters notably associate with variable risks of cardiovascular disease and mortality, however, to date there are no readily available blood tests associated with these parameters. Because of the established parasympathetic contributions towards cardiac regulation, we challenged the working hypothesis that serum acetylcholinesterase (AChE) activity is involved. Methods A total of 403 Healthy men and women were included in the study and underwent treadmill exercise testing. Prior to exercise testing the subject’s serum AChE activity levels were assessed by measuring rates of acetylthiocholine hydrolysis. Results In male subjects AChE activity was positively correlated to resting heart rate (r = 0.210, p = 0.001). Complementing this observation, AChE activity was negatively correlated to the exercise-induced heart rate increase (r = –0.181, p = 0.005) and to heart rate recovery at 1, 2 and 5 minutes following cessation of exercise (r = –0.150, p = 0.022; r = –0.157, p = 0.016; r = –0.176, p = 0.008 respectively). This indicated that lower than average AChE activities, which presumably reflect increased peripheral ACh levels, might be correlated to favorable heart rate parameters. Similar observations were made in female subjects, except for lack of correlation to their resting heart rate. Additionally, we observed that we were able to stratify subjects into two groups of significantly different AChE activity (p = 0.001) based on a cut point of heart rate recovery below 20 beats one minute after cessation of exercise. Conclusion In asymptomatic individuals lower than average AChE activity is associated with favorable indices of exercise-inducible heart rate increase as well as heart rate recovery. Future studies will be needed to evaluate the added prognostic significance gained by implementing this marker into routine practice.

Haploidentical hematopoietic cell transplantation (haplo-HCT) is being increasingly used in acute leukemia patients as an alternative transplant modality when matched sibling or matched unrelated donors are unavailable. As several potential haploidentical relative donors are typically available for a given patient, optimizing donor selection to improve clinical outcome is crucial. The impact of donor age and kinship on the outcome of acute leukemia patients is not clearly established in this setting. Using the multinational registry of the acute leukemia working party of the European society for blood and marrow transplantation we retrospective analyzed the clinical outcome of 1270 acute myeloid leukemia and acute lymphoblastic leukemia patients who underwent haplo-HCT between 2005 and 2015. Patients over the age of 40 were significantly affected by increasing donor age resulting in higher non-relapse mortality (NRM) [Hazard ratio (HR)=1.86, confidence interval (CI) 95%, 1.18-2.94; P = .007], inferior leukemia-free survival (LFS) (HR = 1.59, CI 95%, 1.13-2.24; P = .007), and overall survival (OS) (HR = 1.74, CI 95%, 1.22-2.47; P = .002) when donors were over the age of 40. Additionally, kinship was found to be prognostically significant as patients transplanted from children donors over the age of 35 experienced an increased rate of NRM (HR = 1.82, CI 95%, 1.13-2.9; P = .01), inferior LFS (HR = 1.5, CI 95%, 1.05-2.13; P = .03), and OS (HR = 1.5, CI 95%, 1.04-2.15; P = .03). For patients younger than 40 years, donor age and kinship were mostly not clinically impactful. Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for acute leukemia patients.

ABO incompatibility is commonly observed in stem cell transplantation and its impact in this setting has been extensively investigated. HLA-mismatched unrelated donors (MMURD) are often used as an alternative stem cell source but are associated with increased transplant related complications. Whether ABO incompatibility affects outcome in MMURD transplantation for acute myeloid leukemia (AML) patients is unknown. We evaluated 1,013 AML patients who underwent MMURD transplantation between 2005 and 2014. Engraftment rates were comparable between ABO matched and mismatched patients, as were relapse incidence [34%; 95% confidence interval (CI), 28-39; for ABO matched vs. 36%; 95% CI, 32-40; for ABO mismatched; P = .32], and nonrelapse mortality (28%; 95% CI, 23-33; for ABO matched vs. 25%; 95% CI, 21-29; for ABO mismatched; P = .2). Three year survival was 40% for ABO matched and 43% for ABO mismatched patients (P = .35), Leukemia free survival rates were also comparable between groups (37%; 95% CI, 32-43; for ABO matched vs. 38%; 95% CI, 33-42; for ABO mismatched; P = .87). Incidence of grade II-IV acute graft versus host disease was marginally lower in patients with major ABO mismatching (Hazard ratio of 0.7, 95% CI, 0.5-1; P = .049]. ABO incompatibility probably has no significant clinical implications in MMURD transplantation. ispartof: American Journal of Hematology vol:92 issue:8 pages:789-796 ispartof: location:United States status: published