Pre-Transplant Serum Leptin Levels and Relapse of Acute Myeloid Leukemia After Allogeneic Transplantation

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 26

PMID 35216457

Authors

Mark-Alexander Schwarzbich

Hao Dai

Lambros Kordelas

Dietrich W Beelen

Aleksandar Radujkovic

Carsten Muller-Tidow

Peter Dreger

Thomas Luft

Affiliations

Soon will be listed here.

Abstract

Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). 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. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies ( = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. 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). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59-0.96, = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT.

Citing Articles

The predictive value of T-cell chimerism for disease relapse after allogeneic hematopoietic stem cell transplantation.

Li Z, Wang J, Deng L, Liu X, Kong F, Zhao Y Front Immunol. 2024; 15:1382099.

PMID: 38665912 PMC: 11043518. DOI: 10.3389/fimmu.2024.1382099.

Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges.

Tsilingiris D, Vallianou N, Spyrou N, Kounatidis D, Christodoulatos G, Karampela I Curr Obes Rep. 2023; 13(1):1-34.

PMID: 38159164 PMC: 10933194. DOI: 10.1007/s13679-023-00542-z.

References

Craddock C, Versluis J, Labopin M, Socie G, Huynh A, Deconinck E . Distinct factors determine the kinetics of disease relapse in adults transplanted for acute myeloid leukaemia. J Intern Med. 2017; 283(4):371-379. DOI: 10.1111/joim.12720. View

Mazziotti G, Parkes A, Lage M, Premawardhana L, Casanueva F, Lazarus J . High leptin levels in women developing postpartum thyroiditis. Clin Endocrinol (Oxf). 2004; 60(2):208-13. DOI: 10.1046/j.1365-2265.2003.01966.x. View

Dietrich S, Falk C, Benner A, Karamustafa S, Hahn E, Andrulis M . Endothelial vulnerability and endothelial damage are associated with risk of graft-versus-host disease and response to steroid treatment. Biol Blood Marrow Transplant. 2012; 19(1):22-7. DOI: 10.1016/j.bbmt.2012.09.018. View

Hino M, Nakao T, Yamane T, Ohta K, Takubo T, Tatsumi N . Leptin receptor and leukemia. Leuk Lymphoma. 2000; 36(5-6):457-61. DOI: 10.3109/10428190009148392. View

Weisdorf D, Zhang M, Arora M, Horowitz M, Rizzo J, Eapen M . Graft-versus-host disease induced graft-versus-leukemia effect: greater impact on relapse and disease-free survival after reduced intensity conditioning. Biol Blood Marrow Transplant. 2012; 18(11):1727-33. PMC: 3472079. DOI: 10.1016/j.bbmt.2012.06.014. View

Hahn M, Bottcher S, Dietrich S, Hegenbart U, Rieger M, Stadtherr P . Allogeneic hematopoietic stem cell transplantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse. Bone Marrow Transplant. 2015; 50(10):1279-85. DOI: 10.1038/bmt.2015.150. View

Bulley S, Gassas A, Dupuis L, Aplenc R, Beyene J, Greenberg M . Inferior outcomes for overweight children undergoing allogeneic stem cell transplantation. Br J Haematol. 2007; 140(2):214-7. DOI: 10.1111/j.1365-2141.2007.06900.x. View

Jagasia M, Greinix H, Arora M, Williams K, Wolff D, Cowen E . National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2014; 21(3):389-401.e1. PMC: 4329079. DOI: 10.1016/j.bbmt.2014.12.001. View

Fathi A, Chen Y . Treatment of relapse of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Curr Hematol Malig Rep. 2014; 9(2):186-92. DOI: 10.1007/s11899-014-0209-2. View

10.

Shimizu H, Shimomura Y, Hayashi R, Ohtani K, Sato N, Futawatari T . Serum leptin concentration is associated with total body fat mass, but not abdominal fat distribution. Int J Obes Relat Metab Disord. 1997; 21(7):536-41. DOI: 10.1038/sj.ijo.0800437. View

11.

Vadacca M, Margiotta D, Navarini L, Afeltra A . Leptin in immuno-rheumatological diseases. Cell Mol Immunol. 2011; 8(3):203-12. PMC: 4012876. DOI: 10.1038/cmi.2010.75. View

12.

Radujkovic A, Becker N, Benner A, Penack O, Platzbecker U, Stolzel F . Pre-transplant weight loss predicts inferior outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndrome. Oncotarget. 2015; 6(33):35095-106. PMC: 4741512. DOI: 10.18632/oncotarget.4805. View

13.

Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T . Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer. 2009; 115(20):4715-26. DOI: 10.1002/cncr.24531. View

14.

Gan B, Hu J, Jiang S, Liu Y, Sahin E, Zhuang L . Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature. 2010; 468(7324):701-4. PMC: 3058342. DOI: 10.1038/nature09595. View

15.

Yang J, Xue S, Zhang X, Zhou Y, Qin L, Shen Y . Effect of body mass index on overall survival of patients with allogeneic hematopoietic stem cell transplantation. Eur J Clin Nutr. 2016; 71(6):750-754. DOI: 10.1038/ejcn.2016.225. View

16.

Elmquist J, Elias C, Saper C . From lesions to leptin: hypothalamic control of food intake and body weight. Neuron. 1999; 22(2):221-32. DOI: 10.1016/s0896-6273(00)81084-3. View

17.

Busso N, So A, Chobaz-Peclat V, Morard C, Martinez-Soria E, Talabot-Ayer D . Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis. J Immunol. 2002; 168(2):875-82. DOI: 10.4049/jimmunol.168.2.875. View

18.

Wingard J, Majhail N, Brazauskas R, Wang Z, Sobocinski K, Jacobsohn D . Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011; 29(16):2230-9. PMC: 3107742. DOI: 10.1200/JCO.2010.33.7212. View

19.

Fantuzzi G, Faggioni R . Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol. 2000; 68(4):437-46. View

20.

Otvos Jr L, Shao W, Vanniasinghe A, Amon M, Holub M, Kovalszky I . Toward understanding the role of leptin and leptin receptor antagonism in preclinical models of rheumatoid arthritis. Peptides. 2011; 32(8):1567-74. DOI: 10.1016/j.peptides.2011.06.015. View