Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)

  • A Correction to this article was published on 20 February 2020

Abstract

Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.

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Fig. 1: Decisional tree for the composition of the triple antiemetic prophylaxis in high emetogenic conditioning regimens.

Change history

  • 20 February 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

References

  1. 1.

    Bras G, Hill KR. Veno-occlusive disease of the liver; essential pathology. Lancet. 1956;271:161–3.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018;53:138–45.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Corbacioglu S, Jabbour EJ, Mohty M. Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Biol Blood Marrow Transplant. 2019;25:1271–80.

    PubMed  Article  Google Scholar 

  4. 4.

    Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2016;51:906–12.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Faraci M, Bertaina A, Luksch R, Calore E, Lanino E, Saglio F, et al. Sinusoidal obstruction syndrome/veno-occlusive disease after autologous or allogeneic hematopoietic stem cell transplantation in children: a retrospective study of the Italian Hematology-Oncology Association-Hematopoietic Stem Cell Transplantation Group. Biol Blood Marrow Transplant. 2019;25:313–20.

  6. 6.

    Essell JH, Schroeder MT, Harman GS, Halvorson R, Lew V, Callander N, et al. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128:975–81.

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Gharib MI, Bulley SR, Doyle JJ, Wynn RF. Venous occlusive disease in children. Thromb Res. 2006;118:27–38.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Ohashi K, Tanabe J, Watanabe R, Tanaka T, Sakamaki H, Maruta A, et al. The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation. Am J Hematol. 2000;64:32–8.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Park SH, Lee MH, Lee H, Kim HS, Kim K, Kim WS, et al. A randomized trial of heparin plus ursodiol vs. heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2002;29:137–43.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Ruutu T, Eriksson B, Remes K, Juvonen E, Volin L, Remberger M, et al. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100:1977–83.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012;379:1301–9.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, et al. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 2013;163:444–57.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Al Beihany A, Al Omar H, Sahovic E, Chaudhri N, Al Mohareb F, Al Sharif F, et al. Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone. Bone Marrow Transplant. 2008;41:287–91.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Myers KC, Lawrence J, Marsh RA, Davies SM, Jodele S. High-dose methylprednisolone for veno-occlusive disease of the liver in pediatric hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2013;19:500–3.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Qutob AF, Gue S, Revesz T, Logan RM, Keefe D. Prevention of oral mucositis in children receiving cancer therapy: a systematic review and evidence-based analysis. Oral Oncol. 2013;49:102–7.

    PubMed  Article  Google Scholar 

  16. 16.

    Wallhult E, Quinn B. Early and acute complications and the principles of HSCT nursing care. In: Kenyon M, Babic A, editors. The european blood and marrow transplantation textbook for nurses: under the auspices of EBMT. Cham: Springer International Publishing; 2018. p. 163–95.

  17. 17.

    Tomlinson D, Judd P, Hendershot E, Maloney AM, Sung L. Measurement of oral mucositis in children: a review of the literature. Support Care Cancer. 2007;15:1251–8.

    PubMed  Article  Google Scholar 

  18. 18.

    Quinn B, Potting CM, Stone R, Blijlevens NM, Fliedner M, Margulies A, et al. Guidelines for the assessment of oral mucositis in adult chemotherapy, radiotherapy and haematopoietic stem cell transplant patients. Eur J Cancer. 2008;44:61–72.

    PubMed  Article  Google Scholar 

  19. 19.

    Ethier MC, Regier DA, Tomlinson D, Judd P, Doyle J, Gassas A, et al. Perspectives toward oral mucositis prevention from parents and health care professionals in pediatric cancer. Support Care Cancer. 2012;20:1771–7.

    PubMed  Article  Google Scholar 

  20. 20.

    Harris DJ, Eilers J, Harriman A, Cashavelly BJ, Maxwell C. Putting evidence into practice: evidence-based interventions for the management of oral mucositis. Clin J Oncol Nurs. 2008;12:141–52.

    PubMed  Article  Google Scholar 

  21. 21.

    The modified would be:American Academy of Pediatric Dentistry (AAPD)". Guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation and/or radiation therapy. The reference manual of pediatric dentistry; 37:422–30

  22. 22.

    Chaveli-Lopez B, Bagan-Sebastian JV. Treatment of oral mucositis due to chemotherapy. J Clin Exp Dent. 2016;8:e201–9.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Wang L, Gu Z, Zhai R, Zhao S, Luo L, Li D, et al. Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. PLoS ONE. 2015;10:e0128763.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24.

    Treister N, Nieder M, Baggott C, Olson E, Chen L, Dang H, et al. Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. Br J Cancer. 2017;116:21–7.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Gobbo M, Verzegnassi F, Ronfani L, Zanon D, Melchionda F, Bagattoni S, et al. Multicenter randomized, double-blind controlled trial to evaluate the efficacy of laser therapy for the treatment of severe oral mucositis induced by chemotherapy in children: laMPO RCT. Pediatr Blood Cancer. 2018;65:e27098.

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Vitale MC, Modaffari C, Decembrino N, Zhou FX, Zecca M, Defabianis P. Preliminary study in a new protocol for the treatment of oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) and chemotherapy (CT). Lasers Med Sci. 2017;32:1423–8.

    PubMed  Article  Google Scholar 

  27. 27.

    Langdana A, Tully N, Molloy E, Bourke B, O’Meara A. Intensive enteral nutrition support in paediatric bone marrow transplantation. Bone Marrow Transplant. 2001;27:741–6.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Wilken M. The impact of child tube feeding on maternal emotional state and identity: a qualitative meta-analysis. J Pediatr Nurs. 2012;27:248–55.

    PubMed  Article  Google Scholar 

  29. 29.

    Azarnoush S, Bruno B, Beghin L, Guimber D, Nelken B, Yakoub-Agha I, et al. Enteral nutrition: a first option for nutritional support of children following allo-SCT? Bone Marrow Transplant. 2012;47:1191–5.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Lemal R, Cabrespine A, Pereira B, Combal C, Ravinet A, Hermet E, et al. 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). Trials. 2015;16:136.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  31. 31.

    Gonzales F, Bruno B, Alarcon Fuentes M, De Berranger E, Guimber D, Behal H, et al. Better early outcome with enteral rather than parenteral nutrition in children undergoing MAC allo-SCT. Clin Nutr. 2018;37:2113–21.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Rzepecki P, Barzal J, Oborska S. Blood and marrow transplantation and nutritional support. Support Care Cancer. 2010;18:S57–65.

    PubMed  Article  Google Scholar 

  33. 33.

    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;94:287–94.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Heubi JE. Whenever possible, use the gut! J Pediatr Hematol Oncol. 1999;21:88–90.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    Angelucci E, Pilo F. Management of iron overload before, during, and after hematopoietic stem cell transplantation for thalassemia major. Ann N Y Acad Sci. 2016;1368:115–21.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Majhail NS, Lazarus HM, Burns LJ. Iron overload in hematopoietic cell transplantation. Bone Marrow Transplant. 2008;41:997–1003.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J, et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 2002;100:17–21.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Jastaniah W, Harmatz P, Pakbaz Z, Fischer R, Vichinsky E, Walters MC. Transfusional iron burden and liver toxicity after bone marrow transplantation for acute myelogenous leukemia and hemoglobinopathies. Pediatr Blood Cancer. 2008;50:319–24.

    PubMed  Article  Google Scholar 

  39. 39.

    Taher AT, Saliba AN. Iron overload in thalassemia: different organs at different rates. Hematol Am Soc Hematol Educ Program. 2017;2017:265–71.

    Article  Google Scholar 

  40. 40.

    Angelucci E, Brittenham GM, McLaren CE, Ripalti M, Baronciani D, Giardini C, et al. Hepatic iron concentration and total body iron stores in thalassemia major. N Engl J Med. 2000;343:327–31.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Wood JC. Use of magnetic resonance imaging to monitor iron overload. Hematol Oncol Clin North Am. 2014;28:747–64.

    PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Wood JC. Guidelines for quantifying iron overload. Hematol Am Soc Hematol Educ Program. 2014;2014:210–5.

    Article  Google Scholar 

  43. 43.

    Yesilipek MA, Karasu G, Kaya Z, Kuskonmaz BB, Uygun V, Dag I, et al. A phase II, multicenter, single-arm study to evaluate the safety and efficacy of deferasirox after hematopoietic stem cell transplantation in children with beta-thalassemia major. Biol Blood Marrow Transplant. 2018;24:613–8.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Mariotti E, Angelucci E, Agostini A, Baronciani D, Sgarbi E, Lucarelli G. Evaluation of cardiac status in iron-loaded thalassaemia patients following bone marrow transplantation: improvement in cardiac function during reduction in body iron burden. Br J Haematol. 1998;103:916–21.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Jarisch A, Salzmann-Manrique E, Cario H, Grosse R, Soerensen J, Fischer R, et al. Serum ferritin is not a reliable predictor to determine iron overload in thalassemia major patients post-hematopoietic stem cell transplantation. Eur J Haematol. 2018;101:791–7.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Fischer R, Harmatz PR. Non-invasive assessment of tissue iron overload. Hematology Am Soc Hematol Educ Program. 2009;1:215–21.

  47. 47.

    Navari RM. 5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy. Biochim Biophys Acta. 2015;1848:2738–46.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Berger MJ, Ettinger DS, Aston J, Barbour S, Bergsbaken J, Bierman PJ, et al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017;15:883–93.

    PubMed  Article  Google Scholar 

  49. 49.

    Schnell FM. Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control. Oncologist. 2003;8:187–98.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Dupuis LL, Boodhan S, Holdsworth M, Robinson PD, Hain R, Portwine C, et al. Guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2013;60:1073–82.

    PubMed  Article  Google Scholar 

  51. 51.

    Dupuis LL, Robinson PD, Boodhan S, Holdsworth M, Portwine C, Gibson P, et al. Guideline for the prevention and treatment of anticipatory nausea and vomiting due to chemotherapy in pediatric cancer patients. Pediatr Blood Cancer. 2014;61:1506–12.

    PubMed  Article  Google Scholar 

  52. 52.

    Dupuis LL, Roscoe JA, Olver I, Aapro M, Molassiotis A. 2016 updated MASCC/ESMO consensus recommendations: anticipatory nausea and vomiting in children and adults receiving chemotherapy. Support Care Cancer. 2017;25:317–21. 2017

    PubMed  Article  Google Scholar 

  53. 53.

    Einhorn LH, Rapoport B, Navari RM, Herrstedt J, Brames MJ. 2016 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. Support Care Cancer. 2017;25:303–8. 2017

    PubMed  Article  Google Scholar 

  54. 54.

    Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2017;35:3240–61.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Patel P, Robinson PD, Thackray J, Flank J, Holdsworth MT, Gibson P, et al. Guideline for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric cancer patients: a focused update. Pediatr Blood Cancer. 2017;64:1–12.

  56. 56.

    Dupuis LL, Boodhan S, Sung L, Portwine C, Hain R, McCarthy P, et al. Guideline for the classification of the acute emetogenic potential of antineoplastic medication in pediatric cancer patients. Pediatr Blood Cancer. 2011;57:191–8.

    PubMed  Article  Google Scholar 

  57. 57.

    Morrow GR. Effect of the cognitive hierarchy in the systematic desensitization treatment of anticipatory nausea in cancer patients: a component comparison with relaxation only, counseling, and no treatment. Cogn Ther Res. 1986;10:421–46.

    Article  Google Scholar 

  58. 58.

    Flank J, Robinson PD, Holdsworth M, Phillips R, Portwine C, Gibson P, et al. Guideline for the treatment of breakthrough and the prevention of refractory chemotherapy-induced nausea and vomiting in children with cancer. Pediatr Blood Cancer. 2016;63:1144–51.

    PubMed  Article  Google Scholar 

  59. 59.

    Patel P, Leeder JS, Piquette-Miller M, Dupuis LL. Aprepitant and fosaprepitant drug interactions: a systematic review. Br J Clin Pharmacol. 2017;83:2148–62.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

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Nava, T., Ansari, M., Dalle, J. et al. Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 55, 1126–1136 (2020). https://doi.org/10.1038/s41409-020-0818-4

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