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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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
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
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
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
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.)
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
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
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
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
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
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
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
Ferrara JL, Deeg HJ . Graft-versus-host disease New Engl J Med 1991 324: 667–674
Schultz KR, Green GJ, Wensley D et al. Obstructive lung disease in children after allogeneic bone marrow transplantation Blood 1994 84: 3212–3220
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
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
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
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
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
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
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
Przepiorka D, Weisdorf D, Martin P et al. 1994 Consensus Conference on Acute GVHD Grading Bone Marrow Transplant 1995 15: 825–828
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
Hoyer PF, Brodehl J, Ehrich JH et al. Practical aspects in the use of cyclosporin in paediatric nephrology Pediatr Nephrol 1991 5: 630–638
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Roujeau JC . Pulse glucocorticoid therapy. The ‘big shot’ revisited Arch Dermatol 1996 132: 1499–1502
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
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
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
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
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
Jampel RM, Farmer ER, Vogelsang GB et al. PUVA therapy for chronic cutaneous graft-vs-host disease Arch Dermatol 1991 127: 1673–1678
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
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
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
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
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
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
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
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
Shaw PJ, Afify Z . Rapid tapering of cyclosporin to maximise the graft-versus-leukaemia effect (letter) Bone Marrow Transplant 1999 23: 632–633
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
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
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
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
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
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
Barrett AJ, Horowitz MM, Gale RP et al. Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival Blood 1989 74: 862–871
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
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
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
Bacigalupo A, Maiolino A, Van Lint MT et al. Cyclosporin A and chronic graft versus host disease Bone Marrow Transplant 1990 6: 341–344
Deeg HJ, Henslee-Downey PJ . Management of acute graft-versus-host disease Bone Marrow Transplant 1990 6: 1–8
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
Morton AJ, Durrant ST . Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation Clin Transplant 1995 9: 205–208
Atkinson K, Weller P, Ryman W et al. PUVA therapy for drug-resistant graft-versus-host disease Bone Marrow Transplant 1986 1: 227–236
Acknowledgements
We are grateful to all colleagues who contributed to the proposal for the common GVHD prophylaxis and therapy regimen.
Author information
Authors and Affiliations
Consortia
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1702524
Keywords
This article is cited by
-
Low cyclosporine concentrations in children and time to acute graft versus host disease
BMC Pediatrics (2020)
-
First report of pediatric hematopoietic stem cell transplantation activities in the eastern mediterranean region from 1984 to 2011: on behalf of the pediatric cancer working committee of the eastern mediterranean blood and marrow transplantation group
Bone Marrow Transplantation (2017)
-
Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis
Bone Marrow Transplantation (2016)
-
Folinic acid after MTX as prophylaxis for GVHD in pediatric bone marrow transplantation
International Journal of Hematology (2015)
-
Superior outcome using cyclosporin A alone versus cyclosporin A plus methotrexate for post-transplant immunosuppression in children with acute leukemia undergoing sibling hematopoietic stem cell transplantation
Journal of Cancer Research and Clinical Oncology (2015)