Pre-Conditioning Serum Leptin Levels Predict Early Relapse Rates of High Risk AML after Allogeneic Stem Cell Transplantation
Authors: Schwarzbich Mark-Alexander , Dai Hao , Kordelas Lambros , Beelen Dietrich W. , Radujkovic Aleksandar , Müller-Tidow Carsten , Dreger Peter , Luft Thomas 
Published: October 2019

Abstract
Background: Allogeneic stem cell transplantation (alloSCT) is an effective treatment for many hematologic diseases including intermediate- and high-risk acute myeloid leukemia (AML). Relapse of the original disease continues to be the most common cause of treatment failure following alloSCT for AML. The factors governing relapse and non-relapse mortality (NRM) following alloSCT are poorly understood. We have previously reported that weight loss prior to conditioning therapy is a risk factor for relapse of myeloid diseases following alloSCT (1). The peptide hormone Leptin is a key regulator of food intake and body weight (2). Moreover, it has known roles in regulation of metabolism and immune homeostasis (3). This retrospective study evaluates Leptin as a predictor of survival, relapse and NRM following alloSCT for hematologic malignancies.
Methods: Clinical data and Leptin serum levels measured prior to start of conditioning were collected retrospectively in a cohort of patients transplanted for acute leukemias (AML and ALL, n=206). Findings from this cohort were validated in an independent validation cohort of AML patients transplanted in another institution (n=367). Distribution of serum Leptin levels was highly skewed and thus log2-transformation was applied.
Results: We identified low serum Leptin as an independent predictor for early relapse following alloSCT for intermediate and advanced stage acute leukemia (AML and ALL) as defined by the EBMT score (4). Multivariate analysis of Leptin and known covariables (age at transplantation, HLA mismatch, conditioning intensity, in-vivo T cell depletion with ATG, recipient and donor sex) revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59-0.96, p=0.020) for Leptin. We observed an increased risk of NRM with higher leptin serum levels with an HR of 1.63 (1.15-2.31, p=0.006) while no statistically significant effect on OS was found. In order to visualize the effect of the continuous variable on the distribution of survival times, the quartiles of serum Leptin levels with regards to relapse, NRM and OS are shown in Figure 1. This effect on relapse was similar in intermediate and advanced stage AML patients from an independent cohort with an HR of 0.84 (0.72-0.97, p=0.020) while no statistically significant effects on NRM and OS were found. Pre-conditioning serum Leptin was confirmed as a predictor for early relapse by fitting the Cox model to the validation data.
Conclusion: Low pre-conditioning serum Leptin levels appear to be an independent risk factor for early relapse following alloSCT for intermediate and advanced stage AML. Pre-conditioning serum Leptin should be explored to guide nutritional intervention in AML patients undergoing alloSCT in order to improve transplant success.
References Dietrich S, Radujkovic A, Stolzel F, Falk CS, Benner A, Schaich M, et al. Pretransplant metabolic distress predicts relapse of acute myeloid leukemia after allogeneic stem cell transplantation. Transplantation. 2015;99(5):1065-71. Elmquist JK, Elias CF, Saper CB. From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 1999;22(2):221-32. Procaccini C, La Rocca C, Carbone F, De Rosa V, Galgani M, Matarese G. Leptin as immune mediator: Interaction between neuroendocrine and immune system. Developmental and comparative immunology. 2017;66:120-9. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009;115(20):4715-26.

Disclosures
Beelen: Medac: Consultancy, Other: Travel Support.