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Non-Malignant Disease

Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism

Abstract

In this retrospective study, we evaluated the chimerism status and outcome in 58 patients (64 transplants) with non-malignant diseases. Reduced intensity conditioning (RIC) was given in half of the transplants. Mixed chimerism (MC) was defined as >1% recipient cells. Two consecutive samples showing >30% recipient cells were defined as high chimerism (high MC). Patients with high MC and the management of these patients were analyzed in greater detail. The overall survival rate was 87%. In total, 23 transplants were donor chimerism (DC) and 41 transplants showed some degree of MC. The incidence of MC was 78 and 50% after RIC and myeloablative conditioning, respectively (P=0.04). Acute GVHD of grades II–III was more common in patients with DC (39%) than in patients with MC (8%) (P=0.002). Owing to high MC, donor lymphocyte infusions were given in 17 cases. The level of MC was reduced in seven cases, unchanged in four cases, increased in one case and there was graft rejection in five cases. A second transplant was carried out in six cases with rejections, five are alive and in remission. We conclude that patients with non-malignant diseases, who develop MC after transplant have less acute GVHD. Despite the high incidence of MC, overall survival is promising.

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References

  1. Ringden O, Remberger M, Svahn BM, Barkholt L, Mattsson J, Aschan J et al. Allogeneic hematopoietic stem cell transplantation for inherited disorders: experience in a single center. Transplantation 2006; 81: 718–725.

    Article  PubMed  Google Scholar 

  2. Steward CG, Jarisch A . Haemopoietic stem cell transplantation for genetic disorders. Arch Dis Child 2005; 90: 1259–1263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bader P, Kreyenberg H, Hoelle W, Dueckers G, Kremens B, Dilloo D et al. Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. Bone Marrow Transplant 2004; 33: 815–821.

    Article  CAS  PubMed  Google Scholar 

  4. Mattsson J, Uzunel M, Remberger M, Ringden O . T cell mixed chimerism is significantly correlated to a decreased risk of acute graft-versus-host disease after allogeneic stem cell transplantation. Transplantation 2001; 71: 433–439.

    Article  CAS  PubMed  Google Scholar 

  5. Amrolia PJ, Vulliamy T, Vassiliou G, Lawson S, Bryon J, Kaeda J et al. Analysis of chimaerism in thalassaemic children undergoing stem cell transplantation. Br J Haematol 2001; 114: 219–225.

    Article  CAS  PubMed  Google Scholar 

  6. Peters C, Steward CG . Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant 2003; 31: 229–239.

    Article  CAS  PubMed  Google Scholar 

  7. Srinivasan R, Takahashi Y, McCoy JP, Espinoza-Delgado I, Dorrance C, Igarashi T et al. Overcoming graft rejection in heavily transfused and allo-immunised patients with bone marrow failure syndromes using fludarabine-based haematopoietic cell transplantation. Br J Haematol 2006; 133: 305–314.

    Article  CAS  PubMed  Google Scholar 

  8. Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood 2006; 107: 1233–1236.

    Article  CAS  PubMed  Google Scholar 

  9. Peters C, Balthazor M, Shapiro EG, King RJ, Kollman C, Hegland JD et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996; 87: 4894–4902.

    CAS  PubMed  Google Scholar 

  10. Malm G, Gustafsson B, Berglund G, Lindstrom M, Naess K, Borgstrom B et al. Outcome in six children with mucopolysaccharidosis type IH, Hurler syndrome, after haematopoietic stem cell transplantation (HSCT). Acta Paediatr 2008; 97: 1108–1112.

    Article  PubMed  Google Scholar 

  11. Olerup O, Zetterquist H . HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 h: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation. Tissue Antigens 1992; 39: 225–235.

    Article  CAS  PubMed  Google Scholar 

  12. Shaw PJ, Hugh-Jones K, Hobbs JR, Downie CJ, Barnes R . Busulphan and cyclophosphamide cause little early toxicity during displacement bone marrow transplantation in fifty children. Bone Marrow Transplant 1986; 1: 193–200.

    CAS  PubMed  Google Scholar 

  13. Bitan M, Or R, Shapira MY, Aker M, Resnick IB, Ackerstein A et al. Fludarabine-based reduced intensity conditioning for stem cell transplantation of Fanconi anemia patients from fully matched related and unrelated donors. Biol Blood Marrow Transplant 2006; 12: 712–718.

    Article  CAS  PubMed  Google Scholar 

  14. Mattsson J, Uzunel M, Tammik L, Aschan J, Ringden O . Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation. Leukemia 2001; 15: 1976–1985.

    Article  CAS  PubMed  Google Scholar 

  15. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C et al. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 2002; 99: 4618–4625.

    Article  CAS  PubMed  Google Scholar 

  16. Hochberg EP, Miklos DB, Neuberg D, Eichner DA, McLaughlin SF, Mattes-Ritz A et al. A novel rapid single nucleotide polymorphism (SNP)-based method for assessment of hematopoietic chimerism after allogeneic stem cell transplantation. Blood 2003; 101: 363–369.

    Article  CAS  PubMed  Google Scholar 

  17. Willasch A, Hoelle W, Kreyenberg H, Niethammer D, Handgretinger R, Lang P et al. Outcome of allogeneic stem cell transplantation in children with non-malignant diseases. Haematologica 2006; 91: 788–794.

    PubMed  Google Scholar 

  18. Malm G, Mansson JE, Winiarski J, Mosskin M, Ringden O . Five-year follow-up of two siblings with aspartylglucosaminuria undergoing allogeneic stem-cell transplantation from unrelated donors. Transplantation 2004; 78: 415–419.

    Article  PubMed  Google Scholar 

  19. Boelens JJ, Wynn RF, O′Meara A, Veys P, Bertrand Y, Souillet G et al. Outcomes of hematopoietic stem cell transplantation for Hurler′s syndrome in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant 2007; 40: 225–233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lucarelli G, Gaziev J . Advances in the allogeneic transplantation for thalassemia. Blood Rev 2008; 22: 53–63.

    Article  PubMed  Google Scholar 

  21. Mattsson J, Uzunel M, Brune M, Hentschke P, Barkholt L, Stierner U et al. Mixed chimaerism is common at the time of acute graft-versus-host disease and disease response in patients receiving non-myeloablative conditioning and allogeneic stem cell transplantation. Br J Haematol 2001; 115: 935–944.

    Article  CAS  PubMed  Google Scholar 

  22. Spitzer TR . Nonmyeloablative allogeneic stem cell transplant strategies and the role of mixed chimerism. Oncologist 2000; 5: 215–223.

    Article  CAS  PubMed  Google Scholar 

  23. Valcarcel D, Martino R, Caballero D, Mateos MV, Perez-Simon JA, Canals C et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2003; 31: 387–392.

    Article  CAS  PubMed  Google Scholar 

  24. Jillella AP, Shafer D, Klumpp TR, Emmons RV, Mangan KF . Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; conversion to full donor chimerism. Am J Hematol 2007; 82: 419–426.

    Article  CAS  PubMed  Google Scholar 

  25. Hoelle W, Beck JF, Dueckers G, Kreyenberg H, Lang P, Gruhn B et al. Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia. Bone Marrow Transplant 2004; 33: 219–223.

    Article  CAS  PubMed  Google Scholar 

  26. Remberger M, Ringden O, Ljungman P, Hagglund H, Winiarski J, Lonnqvist B et al. Booster marrow or blood cells for graft failure after allogeneic bone marrow transplantation. Bone Marrow Transplant 1998; 22: 73–78.

    Article  CAS  PubMed  Google Scholar 

  27. Michallet M, Tanguy ML, Socie G, Thiebaut A, Belhabri A, Milpied N et al. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de moelle (SFGM). Br J Haematol 2000; 108: 400–407.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to M Uzunel.

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Svenberg, P., Mattsson, J., Ringdén, O. et al. Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism. Bone Marrow Transplant 44, 757–763 (2009). https://doi.org/10.1038/bmt.2009.82

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