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Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia

A Corrigendum to this article was published on 23 May 2002

Abstract

Allogeneic blood or bone marrow transplantation is a successful treatment for leukaemia and severe aplastic anaemia (SAA). Graft rejection following transplantation for leukaemia is a rare event but leukaemic relapse may occur at varying rates, depending upon the stage of leukaemia at which the transplant was undertaken and the type of leukaemia. Relapse is generally assumed to occur in residual host cells, which are refractory to, or escape from the myeloablative conditioning therapy. Rare cases have been described, however, in which the leukaemia recurs in cells of donor origin. Lack of a successful outcome of blood or bone marrow transplantation for severe aplastic anaemia (SAA), however, is due to late graft rejection or graft-versus-host disease. Leukaemia in cells of donor origin has rarely been reported in patients following allogeneic bone marrow transplantation for SAA. This report describes leukaemic transformation in donor cells following a second allogeneic BMT for severe aplastic anaemia. PCR of short tandem repeats in bone marrow aspirates and in colonies derived from BFUE and CFU-GM indicated the donor origin of leukaemia. Donor leukaemia is a rare event following transplantation for severe aplastic anaemia but may represent the persistence or perturbation of a stromal defect in these patients inducing leukaemic change in donor haemopoietic stem cells.

Bone Marrow Transplantation (2002) 29, 453–456. doi:10.1038/sj.bmt.1703372

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References

  1. Champlin RE, Horowitz MM, van Beckum DW et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results Blood 1989 73: 606 613

    CAS  PubMed  Google Scholar 

  2. Gluckman E, Horowitz MM, Champlin RE et al. Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft versus host disease prophylaxis regimens on outcome Blood 1992 79: 269 275

    CAS  PubMed  Google Scholar 

  3. Klingemann HG, Storb R, Sanders J et al. Acute lymphoblastic leukaemia after bone marrow transplantation for aplastic anaemia Br J Haematol 1986 63: 47 50

    Article  CAS  PubMed  Google Scholar 

  4. Browne PV, Lawler M, Humphries P, McCann SR . Donor-cell leukemia after bone marrow transplantation for severe aplastic anemia New Engl J Med 1991 325: 710 713

    Article  CAS  PubMed  Google Scholar 

  5. Molloy K, Goulden N, Lawler M et al. Patterns of hemopoietic chimerism following BMT for childhood acute lymphoblastic leukaemia from volunteer unrelated donors Blood 1996 87: 3027 3031

    CAS  PubMed  Google Scholar 

  6. Lawler M, Humphries P, McCann SR . Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction Blood 1991 77: 2504 2514

    CAS  PubMed  Google Scholar 

  7. Socié G, Lawler M, McCann SR et al. Chimaerism studies after allogeneic bone marrow transplantation in the polymerase chain reaction era Leuk Res 1995 19: 497 504

    Article  PubMed  Google Scholar 

  8. Bertheas MF, Lafage M, Levy P et al. Influence of mixed chimaerism on the results of allogeneic bone marrow transplantation for leukemia Blood 1991 78: 3103 3106

    CAS  PubMed  Google Scholar 

  9. Roux E, Abdi K, Speiser D et al. Characterisation of mixed chimerism in patients with chronic myeloid leukemia transplanted with T cell depleted marrow: involvement of different hemopoietic lineages before and after relapse Blood 1993 81: 243 248

    CAS  PubMed  Google Scholar 

  10. Fiaklow PJ, Thomas ED, Bryant JI, Neiman PE . Leukaemic transformation of engrafted human marrow cells in vivo Lancet 1971 i: 251 255

    Google Scholar 

  11. Thomas ED, Bryant JL, Buckner CD et al. Leukaemic transformation of engrafted human marrow cells in vivo Lancet 1972 i: 1310 1313

    Article  Google Scholar 

  12. Newburger PE, Latt SA, Pesandro JM et al. Leukemia relapse in donor cells after allogeneic bone marrow transplantation New Engl J Med 1981 304: 712 714

    Article  CAS  PubMed  Google Scholar 

  13. Witherspoon RP, Schubach W, Neiman P et al. Donor cell leukemia developing six years after marrow grafting for acute leukemia Blood 1985 65: 172 174

    Google Scholar 

  14. Schmidz N, Johannsen W, Schmidt G et al. Recurrence of acute lymphoblastic leukemia in donor cells after allogeneic marrow transplantation associated with a deletion of the long arm of chromosome 6 Blood 1987 70: 1099 1104

    Google Scholar 

  15. Zacaria A, Rosti G, Testoni N et al. Chromosome studies in patients with acute nonlymphocytic or acute lymphocytic leukemia submitted to bone marrow transplantation – results of a European cooperative study Cancer Genet Cytogenet 1987 26: 51 58

    Article  Google Scholar 

  16. Feig SA, Dreazen O, Simon M et al. B cell acute lymphoblastic leukemia (ALL) in donor cells following bone marrow transplantation for T cell ALL Bone Marrow Transplant 1988 3: 331 337

    CAS  PubMed  Google Scholar 

  17. Goh K, Klemperer MR . In vivo leukemic transformation: cytogenetic evidence of in vivo leukemic transformation of engrafted marrow cells Am J Hematol 1977 2: 283 290

    Article  CAS  PubMed  Google Scholar 

  18. Elfenbein GJ, Borgaonkar DS, Bias WB et al. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells Blood 1978 52: 627 636

    CAS  PubMed  Google Scholar 

  19. Smith JL, Heerema NA, Provisor AJ . Leukaemic transformation of engrafted bone marrow cells Br J Haematol 1985 60: 415 422

    Article  CAS  PubMed  Google Scholar 

  20. Marmont A, Frassoni F, Bacigalupo A et al. Recurrence of Ph′ positive leukemia in donor cells after marrow transplantation for chronic granulocytic leukemia New Engl J Med 1984 310: 903 906

    Article  CAS  PubMed  Google Scholar 

  21. McCann SR, Lawler M, Humphries P et al. Recurrence of Ph′ positive leukemia in donor cells after marrow transplantation for chronic granulocytic leukemia: confirmation of the donor origin of cells by microsatellite studies Blood 1992 79: 2803 2805

    CAS  PubMed  Google Scholar 

  22. Marks DI, Schwarer AP, Barrett AJ et al. Relapse into blast crisis following bone marrow transplantation for chronic phase chronic myeloid leukaemia. A report of five cases Br J Haematol 1992 81: 378 382

    Article  PubMed  Google Scholar 

  23. Lowsky R, Fyles G, Minden M et al. Detection of donor cell derived acute myelogenous leukaemia in a patient transplanted for chronic myelogenous leukaemia using fluorescence in situ hybridization Br J Haematol 1996 93: 163 165

    Article  CAS  PubMed  Google Scholar 

  24. Cooley LD, Sears DA, Udden MM et al. Donor cell leukemia: report of a case occurring 11 years after allogeneic bone marrow transplantation and review of the literature Am J Hematol 2000 63: 46 53

    Article  CAS  PubMed  Google Scholar 

  25. Katz F, Reeves BR, Alexander S et al. Leukaemia arising in donor cells following allogeneic bone marrow transplantation for beta thalassaemia demonstrated by immunological, DNA and molecular cytogenetic analysis Br J Haematol 1993 85: 326 331

    Article  CAS  PubMed  Google Scholar 

  26. Witherspoon RP, Fisher LD, Schoch G et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia New Engl J Med 1989 321: 784 789

    Article  CAS  PubMed  Google Scholar 

  27. Gosset TC, Gale RP, Fleischman H et al. Immunoblastic sarcoma in donor cells after bone marrow transplantation New Engl J Med 1979 300: 904 907

    Article  Google Scholar 

  28. Shubach WH, Hackman R, Neiman PE et al. A monoclonal immunoblastic sarcoma in donor cells bearing Epstein–Barr virus genomes following allogeneic marrow grafting for acute lymphoblastic leukemia Blood 1982 60: 180 187

    Google Scholar 

  29. Deeg HJ, Sanders J, Martin P et al. Secondary malignancies after marrow transplantation Exp Hematol 1984 12: 660 668

    CAS  PubMed  Google Scholar 

  30. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K . Monoclonal integration of human T cell leukemia provirus in all primary tumors of adult T cell leukemia suggests caustive role of human T-cell leukemia virus in the disease Proc Natl Acad Sci USA 1984 81: 2534 2537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ljungman P, Lawler M, Malm C et al. Infection of donor lymphocytes with HTLV 1 following allogeneic bone marrow transplantation for HTLV 1T cell lymphoma Br J Haematol 1994 88: 403 405

    Article  CAS  PubMed  Google Scholar 

  32. Casciato DA, Scott JL . Acute leukemia following prolonged cytotoxic agent therapy Medicine 1979 58: 32 47

    Article  CAS  PubMed  Google Scholar 

  33. Riche K . Cancinogenicity of antineoplastic drugs in man Cancer Treat Rev 1984 22: 39 67

    Article  Google Scholar 

  34. Socié G, Henry-Amar M, Bacigalupo A et al. Malignant tumors occurring after treatment of aplastic anemia New Engl J Med 1993 329: 1152 1157

    Article  PubMed  Google Scholar 

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Lawler, M., Locasciulli, A., Longoni, D. et al. Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia. Bone Marrow Transplant 29, 453–456 (2002). https://doi.org/10.1038/sj.bmt.1703372

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