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Graft-Versus-Host Disease

Statement of current majority practices in graft-versus-host disease prophylaxis and treatment in children

Abstract

Great variations exist in the prophylaxis and treatment of GVHD in children undergoing allogeneic stem cell transplantation (SCT). The EBMT Working Party Paediatric Diseases (EBMT-WP PD) and the International BFM Study Group – Subcommittee Bone Marrow Transplantation (IBFM-SG), aimed at evaluating current local standards in the prevention and treatment of GVHD and steps which can be taken to achieve a uniform policy for the individual methods. Several conferences with their members assessed practices which are mainly applied or under investigation in children and identified where additional information is needed. For prevention of GVHD, the majority of the paediatric centres prefer CsA ± MTX. Addition of folinic acid to MTX was considered for reduction of side-effects. During treatment of acute GVHD most centres administer prednisolone and whole blood level-adjusted CsA as medications of first choice. In cases of poor or no response to this therapy, additional immunosuppressive agents such as ATG, mycophenolate-mofetile and tacrolimus are being increasingly used. The treatment of chronic GVHD usually consists of various combinations of prednisolone and CsA. In severe cases, extracorporeal photopheresis, psoralene-UVA (PUVA) and thalidomide are administered. Bone Marrow Transplantation (2000) 26, 405–411.

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References

  1. Weisdorf D, Hakke R, Blazar B et al. Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation Transplantation 1991 51: 1197–1203

    Article  CAS  PubMed  Google Scholar 

  2. Kernan NA, Bartsch G, Ash RC et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program New Engl J Med 1993 328: 593–602

    Article  CAS  PubMed  Google Scholar 

  3. Montagna D, Maccario R, Comoli P et al. Frequency of donor cytotoxic T cell precursors does not correlate with occurrence of acute graft-versus-host disease in children transplanted using unrelated donors J Clin Immunol 1996 16: 107–114

    Article  CAS  PubMed  Google Scholar 

  4. Kernan NA, Bordignon C, Heller G et al. Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants Blood 1989 74: 2227–2236

    CAS  PubMed  Google Scholar 

  5. Peters C, Ladenstein R, Ochsenreiter W et al. Survey of GVHD prophylaxis for pediatric stem cell transplantation in Europe: a report from the EBMT Paediatric Diseases Working Party Bone Marrow Transplant 1997 19: 3 (Abstr.)

    Article  Google Scholar 

  6. Slavin S, Ackerstein A, Naparstek E et al. The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? Bone Marrow Transplant 1990 6: 155–161

    CAS  PubMed  Google Scholar 

  7. Aschan J, Ringden O, Andstrom E et al. Individualized prophylaxis against graft-versus-host disease in leukemic marrow transplant recipients Bone Marrow Transplant 1994 14: 79–87

    CAS  PubMed  Google Scholar 

  8. Holler E, Ertl B, Hintermeier-Knabe R et al. Inflammatory reactions induced by pretransplant conditioning – an alternative target for modulation of acute GvHD and complications following allogeneic bone marrow transplantation? Leuk Lymphoma 1997 25: 217–224

    Article  CAS  PubMed  Google Scholar 

  9. Potter MN, Pamphilon DH, Cornish JM et al. Graft-versus-host disease in children receiving HLA-identical allogeneic bone marrow transplants with a low adjusted T lymphocyte dose Bone Marrow Transplant 1991 8: 357–361

    CAS  PubMed  Google Scholar 

  10. Quaglini S, Bellazzi R, Locatelli F et al. An influence diagram for assessing GVHD prophylaxis after bone marrow transplantation in children Med Decis Making 1994 14: 223–235

    Article  CAS  PubMed  Google Scholar 

  11. Ruutu T, Niederwieser D, Gratwohl A et al. A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow Transplantation (EBMT) Bone Marrow Transplant 1997 19: 759–764

    Article  CAS  PubMed  Google Scholar 

  12. Martin PJ, Schoch G, Fisher L et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment Blood 1991 77: 1821–1828

    CAS  PubMed  Google Scholar 

  13. Ferrara JL, Deeg HJ . Graft-versus-host disease New Engl J Med 1991 324: 667–674

    Article  CAS  PubMed  Google Scholar 

  14. Schultz KR, Green GJ, Wensley D et al. Obstructive lung disease in children after allogeneic bone marrow transplantation Blood 1994 84: 3212–3220

    CAS  PubMed  Google Scholar 

  15. Dall'Amico R, Rossetti F, Zulian F et al. Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease Br J Haematol 1997 97: 848–854

    Article  CAS  PubMed  Google Scholar 

  16. Weisdorf D, Haake R, Blazar B et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome Blood 1990 75: 1024–1030

    CAS  PubMed  Google Scholar 

  17. Hings IM, Severson R, Filipovich AH et al. Treatment of moderate and severe acute GVHD after allogeneic bone marrow transplantation Transplantation 1994 58: 437–442

    Article  CAS  PubMed  Google Scholar 

  18. Rovelli A, Arrigo C, Nesi F et al. The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children Bone Marrow Transplant 1998 21: 577–581

    Article  CAS  PubMed  Google Scholar 

  19. Peters C, Ladenstein R, Gadner H et al. Proposal for standard recommendations for prophylaxis of graft-versus-host disease in children. European Group for Blood and Marrow Transplantation (EBMT) Working Party Paediatric Diseases and the International Study Committee of the BFM family – subcommittee Bone Marrow Transplantation (IBFM-STG) Bone Marrow Transplant 1998 Suppl. 2: 57–60

    Google Scholar 

  20. Peters C, Ladenstein R, Minkov M et al. Transplantation activities and treatment strategies in paediatric stem cell transplantation centres: a report from the EBMT Working Party on Paediatric Diseases. European Group for Blood and Marrow Transplantation Bone Marrow Transplant 1998 22: 431–437

    Article  CAS  PubMed  Google Scholar 

  21. Peters C, Ladenstein R, Ochsenreiter W et al. Survey of supportive care standards for paediatric allogeneic stem cell transplantation patients in Europe: a first report from the EBMT Paediatric Diseases Working Party Bone Marrow Transplant 1966 (Suppl. 2) 17–24

  22. Przepiorka D, Weisdorf D, Martin P et al. 1994 Consensus Conference on Acute GVHD Grading Bone Marrow Transplant 1995 15: 825–828

    CAS  PubMed  Google Scholar 

  23. McBride JH, Kim S, Rodgerson DO et al. Conversion of cardiac and liver transplant recipients from HPLC and FPIA (polyclonal) to an FPIA (monoclonal) technique for measurement of blood cyclosporin A J Clin Lab Anal 1998 12: 337–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hoyer PF, Brodehl J, Ehrich JH et al. Practical aspects in the use of cyclosporin in paediatric nephrology Pediatr Nephrol 1991 5: 630–638

    Article  CAS  PubMed  Google Scholar 

  25. Peters C, Matthes-Martin S, Fritsch G et al. Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment Leukemia 1999 13: 2070–2078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Storb R, Etzioni R, Anasetti C et al. Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia Blood 1994 84: 941–949

    CAS  PubMed  Google Scholar 

  27. Schumm M, Lang P, Taylor G et al. Isolation of highly purified autologous and allogeneic peripheral CD34+ cells using the CliniMACS device J Hematother 1999 8: 209–218

    Article  CAS  PubMed  Google Scholar 

  28. Green A, Clarke E, Hunt L et al. Children with acute lymphoblastic leukemia who receive T-cell-depleted HLA mismatched marrow allografts from unrelated donors have an increased incidence of primary graft failure but a similar overall transplant outcome Blood 1999 94: 2236–2246

    CAS  PubMed  Google Scholar 

  29. Michallet M, Perrin MC, Belhabri A et al. Impact of cyclosporine and methylprednisolone dose used for prophylaxis and therapy of graft-versus-host disease on survival and relapse after allogeneic bone marrow transplantation Bone Marrow Transplant 1999 23: 145–150

    Article  CAS  PubMed  Google Scholar 

  30. Van Lint MT, Uderzo C, Locasciulli A et al. Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation Blood 1998 92: 2288–2293

    CAS  PubMed  Google Scholar 

  31. Racadot E, Milpied N, Bordigoni P et al. Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients Bone Marrow Transplant 1995 15: 669–677

    CAS  PubMed  Google Scholar 

  32. Hebart H, Ehninger G, Schmidt H et al. Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies Bone Marrow Transplant 1995 15: 891–894

    CAS  PubMed  Google Scholar 

  33. Stoppa AM, Maraninchi D, Blaise D et al. Anti-LFA1 monoclonal antibody (25.3) for treatment of steroid-resistant grade III-IV acute graft-versus-host disease Transpl Int 1991 4: 3–7

    CAS  PubMed  Google Scholar 

  34. Basara N, Blau WI, Romer E et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients Bone Marrow Transplant 1998 22: 61–65

    Article  CAS  PubMed  Google Scholar 

  35. Ippoliti C, Champlin R, Bugazia N et al. Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies J Clin Oncol 1997 15: 3350–3354

    Article  CAS  PubMed  Google Scholar 

  36. Ely P, Dunitz J, Rogosheske J et al. Use of a somatostatin analogue, octreotide acetate, in the management of acute gastrointestinal graft-versus-host disease Am J Med 1991 90: 707–710

    Article  CAS  PubMed  Google Scholar 

  37. Dall'Amico R, Rossetti F, Zulian F et al. Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease Br J Haematol 1997 97: 848–854

    Article  CAS  PubMed  Google Scholar 

  38. Sullivan KM, Witherspoon RP, Storb R et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease Blood 1988 72: 555–561

    CAS  PubMed  Google Scholar 

  39. Roujeau JC . Pulse glucocorticoid therapy. The ‘big shot’ revisited Arch Dermatol 1996 132: 1499–1502

    Article  CAS  PubMed  Google Scholar 

  40. Vogelsang GB, Farmer ER, Hess AD et al. Thalidomide for the treatment of chronic graft-versus-host disease New Engl J Med 1992 326: 1055–1058

    Article  CAS  PubMed  Google Scholar 

  41. Sullivan KM, Witherspoon RP, Storb R et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation Blood 1988 72: 546–554

    CAS  PubMed  Google Scholar 

  42. Kanamaru A, Takemoto Y, Kakishita E et al. FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Japanese FK506 BMT Study Group Bone Marrow Transplant 1995 15: 885–889

    CAS  PubMed  Google Scholar 

  43. Mookerjee B, Altomonte V, Vogelsang G . Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus Bone Marrow Transplant 1999 24: 517–520

    Article  CAS  PubMed  Google Scholar 

  44. Volc-Platzer B, Honigsmann H, Hinterberger W et al. Photochemotherapy improves chronic cutaneous graft-versus-host disease J Am Acad Dermatol 1990 23: 220–228

    Article  CAS  PubMed  Google Scholar 

  45. Jampel RM, Farmer ER, Vogelsang GB et al. PUVA therapy for chronic cutaneous graft-vs-host disease Arch Dermatol 1991 127: 1673–1678

    Article  CAS  PubMed  Google Scholar 

  46. Rossetti F, Dall'Amico R, Crovetti G et al. Extracorporeal photochemotherapy for the treatment of graft-versus-host disease Bone Marrow Transplant 1996 18: (Suppl.2) 175–181

    PubMed  Google Scholar 

  47. Stockschlaeder M, Storb R, Pepe M et al. A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation Br J Haematol 1992 80: 49–54

    Article  CAS  PubMed  Google Scholar 

  48. Locatelli F, Uderzo C, Dini G et al. Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporin A Bone Marrow Transplant 1993 12: 627–633

    CAS  PubMed  Google Scholar 

  49. Heitger A, Neu N, Kern H et al. Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation Blood 1997 90: 850–857

    CAS  PubMed  Google Scholar 

  50. Petersdorf EW, Gooley TA, Anasetti C et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient Blood 1998 92: 3515–3520

    CAS  PubMed  Google Scholar 

  51. Hows J, Bradley BA, Gore S et al. Prospective evaluation of unrelated donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study Bone Marrow Transplant 1993 12: 371–380

    CAS  PubMed  Google Scholar 

  52. Ringden O, Remberger M, Persson U et al. Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings Bone Marrow Transplant 1995 15: 619–625

    CAS  PubMed  Google Scholar 

  53. Miller KB, Schenkein DP, Comenzo R et al. Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation Ann Hematol 1994 68: 15–20

    Article  CAS  PubMed  Google Scholar 

  54. Shaw PJ, Afify Z . Rapid tapering of cyclosporin to maximise the graft-versus-leukaemia effect (letter) Bone Marrow Transplant 1999 23: 632–633

    Article  CAS  PubMed  Google Scholar 

  55. Ringden O, Hermans J, Labopin M et al. The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT) Leuk Lymphoma 1996 24: 71–79

    Article  CAS  PubMed  Google Scholar 

  56. Locatelli F, Zecca M, Rondelli R et al. Graft-versus-host disease prophylaxis with low-dose cyclosprine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial Blood 2000 95: 1572–1579

    CAS  PubMed  Google Scholar 

  57. Ghalie R, Fitzsimmons WE, Weinstein A et al. Cyclosporine monitoring improves graft-versus-host disease prophylaxis after bone marrow transplantation Ann Pharmacother 1994 28: 379–383

    Article  CAS  PubMed  Google Scholar 

  58. Schmidt H, Ehninger G, Dopfer R et al. Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation Blut 1988 57: 139–142

    Article  CAS  PubMed  Google Scholar 

  59. Yee GC, Self SG, McGuire TR et al. Serum cyclosporine concentration and risk of acute graft-versus-host disease after allogeneic marrow transplantation New Engl J Med 1988 319: 65–70

    Article  CAS  PubMed  Google Scholar 

  60. Carlens S, Aschan J, Remberger M et al. Low-dose cyclosporine of short duration increases the risk of mild and moderate GVHD and reduces the risk of relapse in HLA-identical sibling marrow transplant recipients with leukaemia Bone Marrow Transplant 1999 24: 629–635

    Article  CAS  PubMed  Google Scholar 

  61. Barrett AJ, Horowitz MM, Gale RP et al. Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival Blood 1989 74: 862–871

    CAS  PubMed  Google Scholar 

  62. Peters C, Minkov M, Gadner H et al. Proposal for standard recommendations for prophylaxis of graft-versus-host disease in children. European Group for Blood and Marrow Transplantation (EBMT) Working Party Paediatric Diseases and the International Study Committee of the BFM family-sub-committee Bone Marrow Transplantation (IBFM-STG) Bone Marrow Transplant 1998 21: (Suppl.2) S57–60

    PubMed  Google Scholar 

  63. Russell JA, Woodman RC, Poon MC et al. Addition of low-dose folinic acid to a methotrexate/cyclosporin A regimen for prevention of acute graft-versus-host disease Bone Marrow Transplant 1994 14: 397–401

    CAS  PubMed  Google Scholar 

  64. Remberger M, Svahn B, Hentschke P et al. Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation Bone Marrow Transplant 1999 24: 823–830

    Article  CAS  PubMed  Google Scholar 

  65. Bacigalupo A, Maiolino A, Van Lint MT et al. Cyclosporin A and chronic graft versus host disease Bone Marrow Transplant 1990 6: 341–344

    CAS  PubMed  Google Scholar 

  66. Deeg HJ, Henslee-Downey PJ . Management of acute graft-versus-host disease Bone Marrow Transplant 1990 6: 1–8

    CAS  PubMed  Google Scholar 

  67. Mookerjee B, Altomonte V, Vogelsang G . Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus Bone Marrow Transplant 1999 24: 517–520

    Article  CAS  PubMed  Google Scholar 

  68. Morton AJ, Durrant ST . Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation Clin Transplant 1995 9: 205–208

    CAS  PubMed  Google Scholar 

  69. Atkinson K, Weller P, Ryman W et al. PUVA therapy for drug-resistant graft-versus-host disease Bone Marrow Transplant 1986 1: 227–236

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to all colleagues who contributed to the proposal for the common GVHD prophylaxis and therapy regimen.

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Peters, C., Minkov, M., Gadner, H. et al. Statement of current majority practices in graft-versus-host disease prophylaxis and treatment in children. Bone Marrow Transplant 26, 405–411 (2000). https://doi.org/10.1038/sj.bmt.1702524

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