Since patients undergoing alloSCT represent a heterogeneous group of disease entities, the interaction factor serum Leptin (pg/mL) * disease entity (AML and ALL) was introduced in the Cox model, indicating a significant interaction of serum Leptin levels and the diagnosis of acute leukaemia (AL) (HR (95% CI): 0.83 (0.71–0.99) p = 0.033 Table S2). In the discovery cohort, multivariate Cox regression analysis showed a trend towards lower relapse rates with higher serum Leptin levels (HR per log2 increase (95% CI): 0.91 (0.82–1.00) p = 0.061 Table S1). Pre-Conditioning Serum Leptin Levels Predict Time to Relapse (TTR) Depending on Disease Entity and Disease Stage The known functions of Leptin in metabolism and regulation of immune homeostasis has led us to hypothesize that Leptin levels before alloSCT may be associated with alloSCT outcome.Ģ.1. Leptin is also an important regulator of immune homeostasis. Thus, Leptin plays a crucial role in the pathogenesis of obesity and eating disorders and is thought to mediate the neuroendocrine response to food deprivation. Leptin acts by binding to specific receptors in the hypothalamus and alters expression of several neuropeptides that regulate neuroendocrine function, energy intake and expenditure. Serum levels correlate with total body fat mass. Leptin is a peptide hormone secreted by adipocytes. Similarly, pre-transplant weight loss was associated with poor disease-free and overall survival in patients allografted for myelodysplastic syndrome (MDS). Our group has reported that pre-transplant weight loss and low total serum protein levels independently predicted relapse in patients with acute myeloid leukemia (AML) after alloSCT. Pre-transplant metabolic status is an important and potentially modifiable predictor for 2-year outcome in those patients. Numerous studies have suggested that being either overweight or underweight at alloSCT may affect NRM and survival in both adults and children. Weight and metabolic status can influence outcome after alloSCT. While graft-versus-host disease (GvHD) is known as the main determinant of non-relapse mortality (NRM) after alloSCT, host factors governing relapse following alloSCT are still poorly understood. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT.Īllogeneic stem cell transplantation (alloSCT) is an effective treatment for high-risk hematologic malignancies. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. This effect was similar in an independent validation cohort. Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59–0.96, p = 0.020). Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies ( n = 524) and correlated retrospectively with clinical outcome. This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT).
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