Could enteral nutrition improve the outcome of patients with haematological malignancies undergoing allogeneic haematopoietic stem cell transplantation? A study protocol for a randomized controlled trial (the NEPHA study)

Richard Lemal, Aurélie Cabrespine, Bruno Pereira, Cécile Combal, Aurélie Ravinet, Eric Hermet, Jacques-Olivier Bay, Corinne Bouteloup, Richard Lemal, Aurélie Cabrespine, Bruno Pereira, Cécile Combal, Aurélie Ravinet, Eric Hermet, Jacques-Olivier Bay, Corinne Bouteloup

Abstract

Background: Myeloablative allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a major procedure usually accompanied by multifactorial malnutrition, prompting the recommendation of systematic artificial nutritional support. Parenteral nutrition (PN) is usually administered during allo-HSCT, essentially for practical reasons. Recently published data suggest that enteral nutrition (EN), given as systematic artificial nutrition support, could decrease grade III-IV graft-versus-host disease (GVHD) and infectious events, which are associated with early toxicity after allo-HSCT and then have an impact on early transplant-related mortality (D100 mortality).

Methods/design: We report on the NEPHA trial: an open-label, prospective, randomised, multi-centre study on two parallel groups, which has been designed to evaluate the effect of EN compared to PN on early toxicity after an allo-HSCT procedure. Two hundred forty patients treated with allo-HSCT for a haematological malignancy will be randomly assigned to two groups to receive either EN or PN. The primary endpoint will assess the effect of EN on D100 mortality. Secondary endpoints will compare EN and PN with regards to the main haematological, infectious and nutritional outcomes.

Discussion: The impacts of nutritional support should exceed the limits of nutritional status improvement: EN may directly reduce immunological and infectious events, as well as decrease early transplant-related morbidity and mortality. EN and PN need to be prospectively compared in order to assess their impacts and to provide treatment guidelines. (Clinical trials gov number: NCT01955772; registration: July 19th, 2013).

Figures

Figure 1
Figure 1
Flow chart describing the study’s design.

References

    1. Crowther M, Avenell A, Culligan DJ. Systematic review and meta-analyses of studies of glutamine supplementation in haematopoietic stem cell transplantation. Bone Marrow Transplant. 2009;44(7):413–25. doi: 10.1038/bmt.2009.41.
    1. Mattsson J, Westin S, Edlund S, Remberger M. Poor oral nutrition after allogeneic stem cell transplantation correlates significantly with severe graft-versus-host disease. Bone Marrow Transplant. 2006;38(9):629–33. doi: 10.1038/sj.bmt.1705493.
    1. Malone FR, Leisenring WM, Storer BE, Lawler R, Stern JM, Aker SN, et al. Prolonged anorexia and elevated plasma cytokine levels following myeloablative allogeneic hematopoietic cell transplant. Bone Marrow Transplant. 2007;40(8):765–72. doi: 10.1038/sj.bmt.1705816.
    1. Iestra JA, Fibbe WE, Zwinderman AH, Van Staveren WA, Kromhout D. Body weight recovery, eating difficulties and compliance with dietary advice in the first year after stem cell transplantation: a prospective study. Bone Marrow Transplant. 2002;29(5):417–24. doi: 10.1038/sj.bmt.1703375.
    1. Deeg HJ, Seidel K, Bruemmer B, Pepe MS, Appelbaum FR. Impact of patient weight on non-relapse mortality after marrow transplantation. Bone Marrow Transplant. 1995;15(3):461–8.
    1. Taskinen M, Saarinen UM. Skeletal muscle protein reserve after bone marrow transplantation in children. Bone Marrow Transplant. 1996;18(5):937–41.
    1. Schulte C, Reinhardt W, Beelen D, Mann K, Schaefer U. Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation. Bone Marrow Transplant. 1998;22(12):1171–8. doi: 10.1038/sj.bmt.1701502.
    1. Lobato-Mendizábal E, López-Martínez B, Ruiz-Argüelles GJ. A critical review of the prognostic value of the nutritional status at diagnosis in the outcome of therapy of children with acute lymphoblastic leukemia. Rev Investig Clínica Organo Hosp Enfermedades Nutr. 2003;55(1):31–5.
    1. Ollenschläger G, Thomas W, Konkol K, Diehl V, Roth E. Nutritional behaviour and quality of life during oncological polychemotherapy: results of a prospective study on the efficacy of oral nutrition therapy in patients with acute leukaemia. Eur J Clin Invest. 1992;22(8):546–53. doi: 10.1111/j.1365-2362.1992.tb01504.x.
    1. Horsley P, Bauer J, Gallagher B. Poor nutritional status prior to peripheral blood stem cell transplantation is associated with increased length of hospital stay. Bone Marrow Transplant. 2005;35(11):1113–6. doi: 10.1038/sj.bmt.1704963.
    1. August DA, Huhmann MB. American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr. 2009;33(5):472–500. doi: 10.1177/0148607109341804.
    1. Raynard B, Nitenberg G, Gory-Delabaere G, Bourhis J-H, Bachmann P, Bensadoun R-J, et al. Standards, options and recommendations for nutritional support in bone marrow transplant patients. Bull Cancer (Paris) 2002;89(4):381–98.
    1. Herrmann VM, Petruska PJ. Nutrition support in bone marrow transplant recipients. Nutr Clin Pract Off Publ Am Soc Parenter Enter Nutr. 1993;8(1):19–27.
    1. Lough M, Watkins R, Campbell M, Carr K, Burnett A, Shenkin A. Parenteral nutrition in bone marrow transplantation. Clin Nutr Edinb Scotl. 1990;9(2):97–101. doi: 10.1016/0261-5614(90)90060-6.
    1. Charuhas PM, Fosberg KL, Bruemmer B, Aker SN, Leisenring W, Seidel K, et al. A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: effect on resumption of oral intake after marrow transplantation. JPEN J Parenter Enteral Nutr. 1997;21(3):157–61. doi: 10.1177/0148607197021003157.
    1. Roberts S, Miller J, Pineiro L, Jennings L. Total parenteral nutrition vs oral diet in autologous hematopoietic cell transplant recipients. Bone Marrow Transplant. 2003;32(7):715–21. doi: 10.1038/sj.bmt.1704204.
    1. Weisdorf SA, Lysne J, Wind D, Haake RJ, Sharp HL, Goldman A, et al. Positive effect of prophylactic total parenteral nutrition on long-term outcome of bone marrow transplantation. Transplantation. 1987;43(6):833–8. doi: 10.1097/00007890-198743060-00012.
    1. Braunschweig CL, Levy P, Sheean PM, Wang X. Enteral compared with parenteral nutrition: a meta-analysis. Am J Clin Nutr. 2001;74(4):534–42.
    1. Bozzetti F, Braga M, Gianotti L, Gavazzi C, Mariani L. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: a randomised multicentre trial. Lancet. 2001;358(9292):1487–92. doi: 10.1016/S0140-6736(01)06578-3.
    1. Murray SM, Pindoria S. Nutrition support for bone marrow transplant patients. Cochrane Database Syst Rev. 2009;1:CD002920.
    1. Papadopoulou A, MacDonald A, Williams MD, Darbyshire PJ, Booth IW. Enteral nutrition after bone marrow transplantation. Arch Dis Child. 1997;77(2):131–6. doi: 10.1136/adc.77.2.131.
    1. Sefcick A, Anderton D, Byrne JL, Teahon K, Russell NH. Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study. Bone Marrow Transplant. 2001;28(12):1135–9. doi: 10.1038/sj.bmt.1703301.
    1. Seguy D, Berthon C, Micol J-B, Darré S, Dalle J-H, Neuville S, et al. Enteral feeding and early outcomes of patients undergoing allogeneic stem cell transplantation following myeloablative conditioning. Transplantation. 2006;82(6):835–9. doi: 10.1097/01.tp.0000229419.73428.ff.
    1. Seguy D, Duhamel A, Rejeb MB, Gomez E, Buhl ND, Bruno B, et al. Better outcome of patients undergoing enteral tube feeding after myeloablative conditioning for allogeneic stem cell transplantation. Transplantation. 2012;94(3):287–94. doi: 10.1097/TP.0b013e3182558f60.
    1. Guièze R, Lemal R, Cabrespine A, Hermet E, Tournilhac O, Combal C, et al. Enteral versus parenteral nutritional support in allogeneic haematopoietic stem-cell transplantation. Clin Nutr Edinb Scotl. 31 juill 2013.
    1. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18(4):295–304. doi: 10.1097/00007890-197410000-00001.
    1. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;46(12):1813–21. doi: 10.1086/588660.
    1. Schneider SM, Le Gall P, Girard-Pipau F, Piche T, Pompei A, Nano JL, et al. Total artificial nutrition is associated with major changes in the fecal flora. Eur J Nutr. 2000;39(6):248–55. doi: 10.1007/s003940070003.
    1. Deplancke B, Vidal O, Ganessunker D, Donovan SM, Mackie RI, Gaskins HR. Selective growth of mucolytic bacteria including Clostridium perfringens in a neonatal piglet model of total parenteral nutrition. Am J Clin Nutr. 2002;76(5):1117–25.
    1. Schneider SM, Girard-Pipau F, Anty R, van der Linde EGM, Philipsen-Geerling BJ, Knol J, et al. Effects of total enteral nutrition supplemented with a multi-fibre mix on faecal short-chain fatty acids and microbiota. Clin Nutr Edinb Scotl. 2006;25(1):82–90. doi: 10.1016/j.clnu.2005.09.006.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y-Y, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8. doi: 10.1126/science.1208344.
    1. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–84. doi: 10.1038/nature11319.
    1. Taur Y, Jenq RR, Perales M-A, Littmann ER, Morjaria S, Ling L, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood. 2014;124(7):1174–82. doi: 10.1182/blood-2014-02-554725.
    1. Bredeson CN, Zhang M-J, Agovi M-A, Bacigalupo A, Bahlis NJ, Ballen K, et al. Outcomes following HSCT Using Fludarabine, Busulfan, and Thymoglobulin: A Matched Comparison to Allogeneic Transplants Conditioned with Busulfan and Cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(9):993–1003. doi: 10.1016/j.bbmt.2008.06.009.

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