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Allografting

Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases

Bone Marrow Transplantation volume 42, pages 523–527 (2008)Cite this article

Abstract

Allogeneic blood or marrow transplantation (BMT) is potentially curative for a variety of life-threatening nonmalignant hematologic diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and hemoglobinopathies. The application of BMT to treat these disorders is limited by the lack of suitable donors and often end-organ damage from the underlying disease. We treated three patients with thrombotic PNH, one of whom also had sickle cell disease, with a nonmyeloablative, HLA-haploidentical BMT with post-transplant CY. Rapid engraftment without GVHD occurred in two of the patients, including the patient with sickle cell disease. Both patients are disease free with full donor chimerism and require no immunosuppressive therapy, with follow-up of 1 and 4 years, respectively. Nonmyeloablative, HLA-haploidentical BMT with post-transplant CY is a promising approach for patients with life-threatening nonmalignant hematologic disease who lack an HLA-matched sibling donor.

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References

  1. Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, Gale RP et al. Matched-related donor transplantation for sickle cell disease: report from the center for international blood and transplant research. Br J Haematol 2007; 137: 479–485.

    Article  PubMed  Google Scholar 

  2. Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood 2007; 110: 2749–2756.

    Article  CAS  PubMed  Google Scholar 

  3. Takahashi Y, McCoy Jr JP, Carvallo C, Rivera C, Igarashi T, Srinivasan R et al. In vitro and in vivo evidence of PNH cell sensitivity to immune attack after nonmyeloablative allogeneic hematopoietic cell transplantation. Blood 2004; 103: 1383–1390.

    Article  CAS  PubMed  Google Scholar 

  4. van BK, Bartholomew A, Stock W, Peace D, Devine S, Sher D et al. Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow Transplant 2000; 26: 445–449.

    Article  Google Scholar 

  5. Iannone R, Casella JF, Fuchs EJ, Chen AR, Jones RJ, Woolfrey A et al. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant 2003; 9: 519–528.

    Article  PubMed  Google Scholar 

  6. Horan JT, Liesveld JL, Fenton P, Blumberg N, Walters MC . Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant 2005; 35: 171–177.

    Article  CAS  PubMed  Google Scholar 

  7. Mentzer WC, Heller S, Pearle PR, Hackney E, Vichinsky E . Availability of related donors for bone marrow transplantation in sickle cell anemia. Am J Pediatr Hematol Oncol 1994; 16: 27–29.

    CAS  PubMed  Google Scholar 

  8. Adamkiewicz TV, Szabolcs P, Haight A, Baker KS, Staba S, Kedar A et al. Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience. Pediatr Transplant 2007; 11: 641–644.

    Article  CAS  PubMed  Google Scholar 

  9. Walters MC . Cord blood transplantation for sickle cell anemia: bust or boom? Pediatr Transplant 2007; 11: 582–583.

    Article  PubMed  Google Scholar 

  10. O'Donnell PV, Luznik L, Symons H, Jones RJ, Gooley T, Harrington E et al. Favorable outcome of patients with relapsed Hodgkin lymphoma after nonmyeloablative hematopoietic cell transplantation using related haploidentical donors. Blood 2006; 108: 894a–895a.

    Google Scholar 

  11. O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using post transplantation cyclophosphamide. Biol Blood Marrow Transplant 2002; 8: 377–386.

    Article  CAS  PubMed  Google Scholar 

  12. Crescenzi B, Fizzotti M, Piattoni S, La SR, Matteucci C, Carotti A et al. Interphase FISH for Y chromosome, VNTR polymorphisms, and RT-PCR for BCR-ABL in the monitoring of HLA-matched and mismatched transplants. Cancer Genet Cytogenet 2000; 120: 25–29.

    Article  CAS  PubMed  Google Scholar 

  13. Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993; 260: 812–816.

    Article  CAS  PubMed  Google Scholar 

  14. Sreenan JJ, Pettay JD, Tbakhi A, Totos G, Sandhaus LM, Miller ML et al. The use of amplified variable number of tandem repeats (VNTR) in the detection of chimerism following bone marrow transplantation. A comparison with restriction fragment length polymorphism (RFLP) by Southern blotting. Am J Clin Pathol 1997; 107: 292–298.

    Article  CAS  PubMed  Google Scholar 

  15. Van Deerlin VM, Leonard DG . Bone marrow engraftment analysis after allogeneic bone marrow transplantation. Clin Lab Med 2000; 20: 197–225.

    Article  CAS  PubMed  Google Scholar 

  16. Brodsky RA, Sensenbrenner LL, Jones RJ . Complete remission in acquired severe aplastic anemia following high-dose cyclophosphamide. Blood 1996; 87: 491–494.

    CAS  PubMed  Google Scholar 

  17. Brodsky RA, Petri M, Smith BD, Seifter EJ, Spivak JL, Styler M et al. Immunoablative high-dose cyclophosphamide without stem cell rescue for refractory severe autoimmune disease. Ann Intern Med 1998; 129: 1031–1035.

    Article  CAS  PubMed  Google Scholar 

  18. Brodsky RA, Sensenbrenner LL, Smith BD, Dorr D, Seaman PJ, Karp JE et al. Durable treatment-free remission following high-dose cyclophosphamide for previously untreated severe aplastic anemia. Ann Intern Med 2001; 135: 477–483.

    Article  CAS  PubMed  Google Scholar 

  19. Brodsky RA, Fuller AK, Ratner LE, Leffell MS, Jones RJ . Elimination of alloantibodies by immunoablative high-dose cyclophosphamide. Transplantation 2001; 71: 482–484.

    Article  CAS  PubMed  Google Scholar 

  20. Hilton J . Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res 1984; 44: 5156–5160.

    CAS  PubMed  Google Scholar 

  21. Jones RJ, Barber JP, Vala MS, Collector MI, Kaufmann SH, Ludeman SM et al. Assessment of aldehyde dehydrogenase in viable cells. Blood 1995; 85: 2742–2746.

    CAS  PubMed  Google Scholar 

  22. Mayumi H, Umesue M, Nomoto K . Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology 1996; 195: 129.

    Article  CAS  PubMed  Google Scholar 

  23. Nomoto K, Eto M, Yanaga K, Nishimura Y, Maeda T . Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A. J Immunol 1992; 149: 2668–2674.

    CAS  PubMed  Google Scholar 

  24. Hillmen P, Young NS, Schubert J, Brodsky RA, Socie G, Muus P et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006; 355: 1233–1243.

    Article  CAS  PubMed  Google Scholar 

  25. Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood 2008; 111: 1840–1847.

    Article  CAS  PubMed  Google Scholar 

  26. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L . Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol 2007; 25: 1256–1264.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    R A Brodsky & R J Jones

  2. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    R A Brodsky, L Luznik, J Bolaños-Meade, R J Jones & E J Fuchs

  3. Division of Immunogenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M S Leffell

Authors
  1. R A Brodsky
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  2. L Luznik
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  3. J Bolaños-Meade
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  4. M S Leffell
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  5. R J Jones
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  6. E J Fuchs
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Corresponding author

Correspondence to R A Brodsky.

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Brodsky, R., Luznik, L., Bolaños-Meade, J. et al. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant 42, 523–527 (2008). https://doi.org/10.1038/bmt.2008.203

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