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Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes

Bone Marrow Transplantation volume 50, pages 1168–1172 (2015)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.

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References

  1. Shimamura A . Inherited bone marrow failure syndromes: molecular features. Hematology Am Soc Hematol Educ Program 2006; 1 63–71.

    Article  Google Scholar 

  2. Eapen M, Le Rademacher J, Antin JH, Champlin RE, Carreras J, Fay J et al. Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood 2011; 118: 2618–2621.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bacigalupo A, Socie G, Schrezenmeier H, Tichelli A, Locasciulli A, Fuehrer M et al. Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica 2012; 97: 1142–1148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Peffault de Latour R, Porcher R, Dalle JH, Aljurf M, Korthof ET, Svahn J et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European group for blood and marrow transplantation experience. Blood 2013; 122: 4279–4286.

    Article  CAS  PubMed  Google Scholar 

  5. Gluckman E, Ruggeri A, Volt F, Cunha R, Boudjedir K, Rocha V . Milestones in umbilical cord blood transplantation. Br J Haematol 2011; 154: 441–447.

    Article  PubMed  Google Scholar 

  6. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628–1633.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Locatelli F, Bruno B, Zecca M, Van-Lint MT, McCann S, Arcese W et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial. Blood 2000; 96: 1690–1697.

    CAS  PubMed  Google Scholar 

  8. Bacigalupo A, Socie G, Lanino E, Prete A, Locatelli F, Cesaro F et al. Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA Working Party. Haematologica 2010; 95: 976–982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wagner JE, Eapen M, MacMillan ML, Harris RE, Pasquini R, Boulad F et al. Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia. Blood 2007; 109: 2256–2262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Locatelli F, Zecca M, Pession A, Morreale G, Longoni D, Di Bartolomeo P et al. The outcome of children with Fanconi anemia given hematopoietic stem cell transplantation and the influence of fludarabine in the conditioning regimen: a report from the Italian pediatric group. Haematologica 2007; 92: 1381–1388.

    Article  PubMed  Google Scholar 

  11. Guardiola P, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh JC et al. Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European group for blood and marrow transplantation. Blood 2000; 95: 422–429.

    CAS  PubMed  Google Scholar 

  12. Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87: 386–392.

    CAS  PubMed  Google Scholar 

  13. Ayas M, Saber W, Davies SM, Harris RE, Hale GA, Socie G et al. Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia. J Clin Oncol 2013; 31: 1669–1676.

    Article  PubMed  PubMed Central  Google Scholar 

  14. MacMillan ML, Wagner JE . Haematopoeitic cell transplantation for Fanconi anaemia—when and how? Br J Haematol 2010; 149: 14–21.

    Article  PubMed  Google Scholar 

  15. Alter BP, Caruso JP, Drachtman RA, Uchida T, Velagaleti GV, Elghetany MT et al. Fanconi anemia: myelodysplasia as a predictor of outcome. Cancer Genet Cytogenet 2000; 117: 125–131.

    Article  CAS  PubMed  Google Scholar 

  16. Benajiba L, Salvado C, Dalle JH, Jubert C, Galambrun C, Soulier J et al. HLA-matched related-donor HSCT in Fanconi anemia patients conditioned with cyclophosphamide and fludarabine. Blood 2015; 125: 417–418.

    Article  CAS  PubMed  Google Scholar 

  17. Mitchell R, Wagner JE, Hirsch B, DeFor TE, Zierhut H, MacMillan ML et al. Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia. Br J Haematol 2014; 164: 384–395.

    Article  CAS  PubMed  Google Scholar 

  18. Talbot A, Peffault de Latour R, Raffoux E, Buchbinder N, Vigouroux S, Milpied N et al. Sequential treatment for allogeneic hematopoietic stem cell transplantation in Fanconi anemia with acute myeloid leukemia. Haematologica 2014; 99: e199–e200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mason PJ, Bessler M . The genetics of dyskeratosis congenita. Cancer Genet 2011; 204: 635–645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I . Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am J Hum Genet 2013; 92: 448–453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rocha V, Devergie A, Socie G, Ribaud P, Espérou H, Parquet N et al. Unusual complications after bone marrow transplantation for dyskeratosis congenita. Br J Haematol 1998; 103: 243–248.

    Article  CAS  PubMed  Google Scholar 

  22. Savage SA, Alter BP . Dyskeratosis congenita. Hematol Oncol Clin North Am 2009; 23: 215–231.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gadalla SM, Sales-Bonfim C, Carreras J, Alter BP, Antin JH, Ayas M et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita. Biol Blood Marrow Transplant 2013; 19: 1238–1243.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Amarasinghe K, Dalley C, Dokal I, Laurie A, Gupta V, Marsh J . Late death after unrelated-BMT for dyskeratosis congenita following conditioning with alemtuzumab, fludarabine and melphalan. Bone Marrow Transplant 2007; 40: 913–914.

    Article  CAS  PubMed  Google Scholar 

  25. Kostmann R . Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr Suppl 1956; 45: 1–78.

    Article  CAS  PubMed  Google Scholar 

  26. Bonilla MA, Gillio AP, Ruggeiro M, Kernan NA, Brochstein JA, Abboud M et al. Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 1989; 320: 1574–1580.

    Article  CAS  PubMed  Google Scholar 

  27. Ferry C, Ouachee M, Leblanc T, Michel G, Notz-Carrére A, Tabrizi R et al. Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. Bone Marrow Transplant 2005; 35: 45–50.

    Article  CAS  PubMed  Google Scholar 

  28. Zeidler C, Welte K, Barak Y, Barriga F, Bolyard AA, Boxer L et al. Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation. Blood 2000; 95: 1195–1198.

    CAS  PubMed  Google Scholar 

  29. Donadieu J, Leblanc T, Bader Meunier B, Barkaoui M, Fenneteau O, Bertrand Y et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. Haematologica 2005; 90: 45–53.

    PubMed  Google Scholar 

  30. Pasquet M, Bellanne-Chantelot C, Tavitian S, Prade N, Beaupain B, Larochelle O et al. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood 2013; 121: 822–829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Connelly JA, Choi SW, Levine JE . Hematopoietic stem cell transplantation for severe congenital neutropenia. Curr Opin Hematol 2012; 19: 44–51.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Germeshausen M, Ballmaier M, Schulze H, Welte K, Flohr T, Beiske K et al. Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropenia. Blood 2001; 97: 829–830.

    Article  CAS  PubMed  Google Scholar 

  33. Dror Y, Donadieu J, Koglmeier J, Dodge J, Toiviainen-Salo S, Makitie O et al. Draft consensus guidelines for diagnosis and treatment of Shwachman–Diamond syndrome. Ann NY Acad Sci 2011; 1242: 40–55.

    Article  PubMed  Google Scholar 

  34. Cesaro S, Oneto R, Messina C, Gibson BE, Buzyn A, Steward C et al. Haematopoietic stem cell transplantation for Shwachman–Diamond disease: a study from the European Group for blood and marrow transplantation. Br J Haematol 2005; 131: 231–236.

    Article  PubMed  Google Scholar 

  35. Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L et al. Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman–Diamond syndrome. Bone Marrow Transplant 2008; 42: 159–165.

    Article  CAS  PubMed  Google Scholar 

  36. Donadieu J, Michel G, Merlin E, Bordigoni P, Monteux B, Beaupain B et al. Hematopoietic stem cell transplantation for Shwachman–Diamond syndrome: experience of the French neutropenia registry. Bone Marrow Transplant 2005; 36: 787–792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA et al. Response of Diamond–Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood 2002; 100: 2687–2691.

    Article  CAS  PubMed  Google Scholar 

  38. Vlachos A, Muir E . How I treat Diamond–Blackfan anemia. Blood 116: 3715–3723.

  39. Ballmaier M, Germeshausen M . Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost 2011; 37: 673–681.

    Article  CAS  PubMed  Google Scholar 

  40. Fahd M, Dalissier A, Alahmari AA, Cornish J, Sedlaçek P, Yaniv I et al. Allogeneic stem cell transplantation in amegacaryocytosis: results of a retrospective study in EBMT centers. 40th Annual Meeting of the European Society for Blood and Marrow Transplantation 30 March–2 April 2014. Milan, Italy, Oral presentation.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Service d’Hématologie Greffe, Hôpital Saint-Louis, AP-HP, Paris, France

    R Peffault de Latour

  2. Stem Cell Transplantation Unit, St Anna Children’s Hospital, Vienna, Austria

    C Peters & A Lawitschka

  3. Royal Hospital for Sick Children, Glasgow, Scotland

    B Gibson

  4. Department of Pediatrics and Adolescent Medicine, Pediatric Hematology and Oncology, University Medical Centre, Freiburg, Germany

    B Strahm

  5. Department of Pediatrics, Division of Immuno-Hematology and Stem Cell Transplantation, Leiden University Medical Centre, Leiden, The Netherlands

    A Lankester

  6. Servicio de Oncología y Hematología Pediátricas, Hospital Vall d’Hebron, Barcelona, Spain

    C D de Heredia

  7. Bone Marrow Transplantation Unit, San Gerardo Hospital, Monza, Italy

    D Longoni

  8. Dipartimento di Emato Oncologia Pediatrica, Ematologia Clinica e di Laboratorio, IRCCS Istituto G. Gaslini, Genova, Italy

    F Fioredda

  9. Dipartimento di Onco-Ematologia Pediatrica e Medicina Trasfusionale, U.O. di Oncologia Pediatrica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy

    F Locatelli

  10. Pediatric Hematology Oncology and Stem Cell Transplantation Division, Schneider Children's Medical Centre of Israel, Sackler Faculty of Medicine Tel Aviv University, Petah Tikva, Israel

    I Yaniv

  11. Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland

    J Wachowiak

  12. Service d'Hémato-Oncologie Pédiatrique, Hopital Trousseau AP-HP, Paris Registre des neutropénies, Centre de référence des déficits immunitaires héréditaires (neutropénies), Paris, France

    J Donadieu

  13. BMT-Unit, University Medical Centre Utrecht Pediatrics, Utrecht, The Netherlands

    M Bierings

  14. Department of Pediatrics, Hematology and Oncology, University of Freiburg, Freiburg, Germany

    M Wlodarski

  15. Pediatric Hematology, Oncology and Stem Cell Transplantation, Children's Hospital, University of Regensburg, Regensburg, Germany

    S Corbacioglu

  16. Pediatric Hematology Unit, San Gerardo Hospital, Monza, Italy

    S Bonanomi

  17. Pediatric Hematology, Great Ormond Street Hospital, London, UK

    S Samarasinghe

  18. Service d’hémato-immunologie pédiatrique, GH Robert-Debré, AP-HP, Paris, France

    T Leblanc & J-H Dalle

  19. Pediatric Hematology, G. Gaslini Institute, Genova, Italy

    C Dufour

  20. Université Paris Diderot—Paris 7, Pres Paris-Cité Sorbonne, Paris, France

    J-H Dalle

Authors
  1. R Peffault de Latour
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  2. C Peters
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  3. B Gibson
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  4. B Strahm
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  8. F Fioredda
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  9. F Locatelli
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  19. T Leblanc
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  21. J-H Dalle
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Consortia

on behalf of the Pediatric Working Party (PDWP) and the Severe Aplastic Anemia Working Party (SAAWP) of the European Group for Blood and Marrow Transplantation (EBMT)

Corresponding author

Correspondence to R Peffault de Latour.

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The authors declare no conflict of interest.

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Author contributions

Conception and design: CP, J-HD; provision of study materials and patients: RPL, CP, BG, BS, AL, CDH, DL, FF, FL, IY, JW, JD, AL, MB, MW, SC, SB, SS, TL, CD, J-HD; data collection and assembly: RPL, J-HD; data analysis and interpretation: RPL, CP, BG, BS, AL, CDH, DL, FF, FL, IY, JW, JD, AL, MB, MW, SC, SB, SS, TL, CD, J-HD; manuscript: RPL, CP, J-HD; final approval of manuscript: RPL, CP, BG, BS, AL, CDH, DL, FF, FL, IY, JW, JD, AL, MB, MW, SC, SB, TL, CD, J-HD.

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Peffault de Latour, R., Peters, C., Gibson, B. et al. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Bone Marrow Transplant 50, 1168–1172 (2015). https://doi.org/10.1038/bmt.2015.117

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