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Graft-Versus-Host Disease

Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies

Abstract

Prevention of GVHD is one of the most desirable goals of BMT in aplastic anemia (AA). We reviewed the medical records of 24 consecutive patients treated with BMT for acquired AA using two different GVHD prevention strategies. Ten patients were given alemtuzumab-based GVHD prophylaxis (50–60 mg in three divided doses on days −8, −7 and −6), and 14 patients were given conventional GVHD prophylaxis with calcineurin inhibitors plus MTX before the introduction of the alemtuzumab-based protocols. The incidence of acute, chronic and ‘serious GVHD’ was significantly reduced in alemtuzumab-treated patients compared to conventionally treated patients [11 vs 64% (P=0.03), 0 vs 78% (P=0.002) and 0 vs 57% (P=0.007), respectively]. Engraftment time and rates of graft failure appeared similar in the two groups. A significantly higher proportion of alemtuzumab-treated patients developed CMV reactivation compared to control patients (83 vs 12%; P=0.03); none developed CMV disease. The rates of other infectious complications did not appear significantly different. Our data suggest that 50–60 mg of alemtuzumab given according to the current schedule significantly reduces the risk of GVHD without increasing the risk of graft failure or serious infections.

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References

  1. Storb R, Deeg HJ, Farewell V, Doney K, Appelbaum F, Beatty P et al. Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease. Blood 1986; 68: 119–125.

    CAS  PubMed  Google Scholar 

  2. Storb R, Leisenring W, Deeg HJ, Anasetti C, Appelbaum F, Bensinger W et al. Long-term follow-up of a randomized trial of graft-versus-host disease prevention by methotrexate/cyclosporine versus methotrexate alone in patients given marrow grafts for severe aplastic anemia. Blood 1994; 83: 2749–2750.

    CAS  PubMed  Google Scholar 

  3. 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 

  4. Storb R, Blume KG, O'Donnell MR, Chauncey T, Forman SJ, Deeg HJ et al. Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers. Biol Blood Marrow Transplant 2001; 7: 39–44.

    Article  CAS  PubMed  Google Scholar 

  5. Ades L, Mary JY, Robin M, Ferry C, Porcher R, Esperou H et al. Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood 2004; 103: 2490–2497.

    Article  CAS  PubMed  Google Scholar 

  6. Deeg HJ, Leisenring W, Storb R, Nims J, Flowers ME, Witherspoon RP et al. Long-term outcome after marrow transplantation for severe aplastic anemia. Blood 1998; 91: 3637–3645.

    CAS  PubMed  Google Scholar 

  7. Syrjala KL, Langer SL, Abrams JR, Storer B, Sanders JE, Flowers ME et al. Recovery and long-term function after hematopoietic cell transplantation for leukemia or lymphoma. JAMA 2004; 291: 2335–2343.

    Article  CAS  PubMed  Google Scholar 

  8. Gupta V, Ball SE, Yi QL, Sage D, McCann SR, Lawler M et al. Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia. Biol Blood Marrow Transplant 2004; 10: 867–876.

    Article  CAS  PubMed  Google Scholar 

  9. Gupta V, Ball SE, Sage D, Ortin M, Freires M, Gordon-Smith EC et al. Marrow transplants from matched unrelated donors for aplastic anaemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning. Bone Marrow Transplant 2005; 35: 467–471.

    Article  CAS  PubMed  Google Scholar 

  10. Avivi I, Chakrabarti S, Milligan DW, Waldmann H, Hale G, Osman H et al. Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab. Biol Blood Marrow Transplant 2004; 10: 186–194.

    Article  PubMed  Google Scholar 

  11. Chakrabarti S, Avivi I, Mackinnon S, Ward K, Kottaridis PD, Osman H et al. Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality. Br J Haematol 2002; 119: 1125–1132.

    Article  PubMed  Google Scholar 

  12. Chakrabarti S, Mackinnon S, Chopra R, Kottaridis PD, Peggs K, O'Gorman P et al. High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 2002; 99: 4357–4363.

    Article  CAS  PubMed  Google Scholar 

  13. Rzepecki P, Sarosiek T, Szczylik C . Alemtuzumab, fludarabine and melphalan as a conditioning therapy in severe aplastic anemia and hypoplastic myelodysplastic syndrome—single center experience. Jpn J Clin Oncol 2006; 36: 46–49.

    Article  PubMed  Google Scholar 

  14. Juliusson G, Theorin N, Karlsson K, Frodin U, Malm C . Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival. Bone Marrow Transplant 2006; 37: 503–510.

    Article  CAS  PubMed  Google Scholar 

  15. Incidence of aplastic anemia: the relevance of diagnostic criteria. By the International Agranulocytosis and Aplastic Anemia Study. Blood 1987; 70: 1718–1721.

  16. Gerrie A, Marsh J, Lipton JH, Messner H, Gupta V . Marrow transplantation for severe aplastic anemia with significant renal impairment. Bone Marrow Transplant 2007; 39: 311–313.

    Article  CAS  PubMed  Google Scholar 

  17. Bearman SI, Appelbaum FR, Buckner CD, Petersen FB, Fisher LD, Clift RA et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.

    Article  CAS  PubMed  Google Scholar 

  18. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  19. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  20. Flowers ME, Traina F, Storer B, Maris M, Bethge WA, Carpenter P et al. Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning. Bone Marrow Transplant 2005; 35: 277–282.

    Article  CAS  PubMed  Google Scholar 

  21. Gupta V, Daly A, Lipton JH, Hasegawa W, Chun K, Kamel-Reid S et al. Nonmyeloablative stem cell transplantation for myelodysplastic syndrome or acute myeloid leukemia in patients 60 years or older. Biol Blood Marrow Transplant 2005; 11: 764–772.

    Article  PubMed  Google Scholar 

  22. Nollet F, Billiet J, Selleslag D, Criel A . Standardisation of multiplex fluorescent short tandem repeat analysis for chimerism testing. Bone Marrow Transplant 2001; 28: 511–518.

    Article  CAS  PubMed  Google Scholar 

  23. Passweg JR, Socie G, Hinterberger W, Bacigalupo A, Biggs JC, Camitta BM et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved? Blood 1997; 90: 858–864.

    CAS  PubMed  Google Scholar 

  24. George B, Mathews V, Viswabandya A, Kavitha ML, Srivastava A, Chandy M . Fludarabine and cyclophosphamide based reduced intensity conditioning (RIC) regimens reduce rejection and improve outcome in Indian patients undergoing allogeneic stem cell transplantation for severe aplastic anemia. Bone Marrow Transplant 2007; 40: 13–18.

    Article  CAS  PubMed  Google Scholar 

  25. Cutler C, Li S, Kim HT, Laglenne P, Szeto KC, Hoffmeister L et al. Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort study of methotrexate- and non-methotrexate-containing graft-versus-host disease prophylaxis regimens. Biol Blood Marrow Transplant 2005; 11: 383–388.

    Article  CAS  PubMed  Google Scholar 

  26. Chakrabarti S, Buyck H, Ball S, O'Regan L, Rice P, Marsh J . Epstein-Barr virus associated lymphoproliferative disorder following allogeneic transplantation for acquired aplastic anaemia: the role of prior immunosuppressive therapy and intensity of conditioning. Bone Marrow Transplant 2007; 39 (Suppl. 1): S165 (abstr. 709).

    Google Scholar 

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Acknowledgements

DS received a Trainee Research Award from the American Society of Hematology in support of this project.

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Correspondence to V Gupta.

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Off-label use of alemtuzumab, VG received a research grant from Berlex and Bayer, Canada.

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Siegal, D., Xu, W., Sutherland, R. et al. Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies. Bone Marrow Transplant 42, 51–56 (2008). https://doi.org/10.1038/bmt.2008.88

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