Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Mini Review
  • Published:

Transmission of donor illness by stem cell transplantation: should screening be different in older donors?

Summary:

With increasing donor age, the potential of transmitting diseases from donor to recipient reaches new dimensions. Potentially transmittable diseases from donors include infections, congenital disorders, and acquired illnesses like autoimmune diseases or malignancies of hematological or nonhematological origin. While established nonmalignant or malignant diseases might be easy to discover, early-stage hematological diseases like CML, light-chain multiple myelomas, aleukemic leukemias, occult myelodysplastic syndromes and other malignant and nonmalignant diseases might not be detectable by routine screening but only by invasive, new and/or expensive diagnostic tests. In the following article, we propose recommendations for donor work-up, taking into consideration the age of the donors. In contrast to blood transfusions, stem cells from donors with abnormal findings might still be acceptable for HCT, when no other options are available and life expectancy is limited. This issue is discussed in detail in relation to the available donor and stem cell source. Finally, the recommendations presented here aim at harmonized worldwide work-up for donors to insure high standard quality.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Thomas ED, Storb R, Clift RA et al. Bone-marrow transplantation. N Engl J Med 1975; 292: 1–19.

    Article  Google Scholar 

  2. Gratwohl A, Baldomero H, Passweg J et al. Hematopoietic stem cell transplantation for hematological malignancies in Europe. Leukemia 2003; 17: 941–959.

    Article  CAS  Google Scholar 

  3. Petersdorf EW, Gooley TA, Anasetti C et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 1998; 92: 3515–3520.

    CAS  Google Scholar 

  4. Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  Google Scholar 

  5. Khouri I, Keating M, Korbling M et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies [see comments]. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  Google Scholar 

  6. Chakraverty R, Peggs K, Chopra R et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood 2002; 99: 1071–1078.

    Article  CAS  Google Scholar 

  7. Giralt S, Thall PF, Khouri I et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

    Article  CAS  Google Scholar 

  8. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  Google Scholar 

  9. Niederwieser D, Maris M, Shizuru JA et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

    Article  CAS  Google Scholar 

  10. Kernan NA, Bartsch G, Ash RC et al. Analysis of 462 transplantations from unrelated donors facilitated by the national marrow donor program. N Engl J Med 1993; 328: 593–602.

    Article  CAS  Google Scholar 

  11. Hansen J, Gooley TA, Martin PJ et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998; 338: 962–968.

    Article  CAS  Google Scholar 

  12. Hillyer CD, Josephson CD, Blajchman MA et al. Bacterial contamination of blood components: risks, strategies, and regulation. Joint ASH and AABB Educational Session in Transfusion Medicine. Hematology (Am Soc Hematol Educ Program) 2003; 1: 575–589.

    Article  Google Scholar 

  13. Ljungman P, Lawler M, Asjo B et al. Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia. Br J Haematol 1994; 88: 403–405.

    Article  CAS  Google Scholar 

  14. Ljungman P, Reusser P, de la Camara R et al. Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant 2004; 77: 526–531.

    Google Scholar 

  15. Ljungman P, Brand R, Einsele H et al. Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood 2003; 102: 4255–4260.

    Article  CAS  Google Scholar 

  16. Kollman C, Howe RB, Anasetti C et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2003; 98: 2043–2051.

    Article  Google Scholar 

  17. Heegaard ED, Laub Petersen B . Parvovirus B19 transmitted by bone marrow. Br J Haematol 2000; 111: 659–661.

    Article  CAS  Google Scholar 

  18. Iwamoto M, Jernigan DB, Guasch A et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med 2003; 348: 2196–2203.

    Article  Google Scholar 

  19. Sampathkumar P . West Nile virus: epidemiology, clinical presentation, diagnosis, and prevention. Mayo Clin Proc 2003; 78: 1137–1143.

    Article  Google Scholar 

  20. Ertem M, Kurekci AE, Aysev D et al. Brucellosis transmitted by bone marrow transplantation. Bone Marrow Transplant 2000; 26: 225–226.

    Article  CAS  Google Scholar 

  21. Martino R, Bretagne S, Einsele H et al. Reactivation of toxoplasmosis infection after allogeneic hematopoietic stem cell transplantation (HSCT). A prospective study by the European Group for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party (IDWP). Blood 2003; 102: 687.

    Google Scholar 

  22. Chandrasekar PH, Momin F . Disseminated toxoplasmosis in marrow recipients: a report of three cases and a review of the literature. Bone Marrow Transplant 1997; 19: 685–689.

    Article  CAS  Google Scholar 

  23. Mungai M, Tegtmeier G, Chamberland M, Parise M . Transfusion-transmitted malaria in the United States from 1963 through 1999. N Engl J Med 2001; 344: 1973–1978.

    Article  CAS  Google Scholar 

  24. O'Donnell J, Goldman JM, Wagner K et al. Donor-derived Plasmodium vivax infection following volunteer unrelated bone marrow transplantation. Bone Marrow Transplant 1998; 21: 313–314.

    Article  CAS  Google Scholar 

  25. Dharamasena F, Gordon-Smith E . Transmission of malaria by bone marrow transplantation. Transplantation 1986; 42: 228.

    Article  Google Scholar 

  26. Salutari P, Sica S, Chiusolo P et al. Plasmodium vivax malaria after autologous bone marrow transplantation: an unusual complication. Bone Marrow Transplant 1996; 18: 473–474.

    Google Scholar 

  27. Gratwohl A, Cornu P, Speck B . Bone marrow transplantation from a donor with Gaucher's disease. Transplantation 1979; 28: 266.

    Article  CAS  Google Scholar 

  28. Smith CI, Aarli JA, Bieberfeld P et al. Myasthenia gravis after bone-marrow transplantation. Evidence for a donor origin. N Engl J Med 1983; 309: 1565–1568.

    Article  CAS  Google Scholar 

  29. Bellou A, Kanny G, Fremont S, Moneret-Vautrin DA . Transfer of atopy following bone marrow transplantation. Ann Allergy Asthma Immunol 1997; 78: 513–516.

    Article  CAS  Google Scholar 

  30. Sturfelt G, Lenhoff S, Sallerfors B et al. Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): successful outcome in the recipient and induction of an SLE flare in the donor. Ann Rheum Dis 1996; 55: 638–641.

    Article  CAS  Google Scholar 

  31. Thomson JA, Wilson RM, Franklin IM . Transmission of thyrotoxicosis of autoimmune type by sibling allogeneic bone marrow transplant. Eur J Endocrinol 1995; 133: 564–566.

    Article  CAS  Google Scholar 

  32. Aldouri MA, Ruggieri R, Epstein O, Prentice HG . Adoptive transfer of hyperthyroidism and autoimmune thyroiditis following allogeneic bone marrow transplantation chronic myeloid leukaemia. Br J Haematol 1990; 74: 118–119.

    Article  CAS  Google Scholar 

  33. Kishimoto Y, Yamamoto Y, Ito T et al. Transfer of autoimmune thyroiditis and resolution of palmoplantar pustular psoriasis following allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 19: 1041–1043.

    Article  CAS  Google Scholar 

  34. Lampeter EF, McCann SR, Kolb H . Transfer of diabetes type 1 by bone marrow transplantation. Lancet 1998; 351: 568–569.

    Article  CAS  Google Scholar 

  35. Heyll A, Meckenstock G, Aul C et al. Possible transmission of sarcoidosis via allogeneic bone marrow transplantation. Bone Marrow Transplant 1994; 14: 161–164.

    CAS  Google Scholar 

  36. Bargetzi M, Schönberger A, Tichelli A et al. Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation. Bone Marrow Transplant 1997; 20: 607–609.

    Article  CAS  Google Scholar 

  37. Minchinton RM, Waters AH, Kendra J, Barrett AJ . Autoimmune thrombocytopenia acquired from an allogeneic bone marrow graft. Lancet 1982; 627.

  38. Niederwieser D, Appelbaum FR, Gastl G et al. Inadvertent transmission of a donor's acute myeloid leukemia in bone marrow transplantation for chronic myelocytic leukemia. N Engl J Med 1990; 322: 1794–1796.

    Article  CAS  Google Scholar 

  39. Baron F, Dresse M-F, Beguin Y . Transmission of chronic myeloid leukemia through peripheral-blood stem-cell transplantation. N Engl J Med 2003; 349: 913–914.

    Article  Google Scholar 

  40. Winter TC, Keller PR, Lee FT, Pozniak MA . Donor-derived malignancy: transmission of small-cell lung cancer via renal transplantation. J Ultrasound Med 2001; 20: 559–562.

    Article  CAS  Google Scholar 

  41. Frank S, Müller J, Bonk C et al. Transmission of glioblastoma multiforme through liver transplantation. Lancet 1998; 352: 31.

    Article  CAS  Google Scholar 

  42. Ljungman P . Risk of cytomegalovirus transmission by blood products to immunocompromised patients and means for reduction. Br J Haematol 2004; 125: 107–116.

    Article  Google Scholar 

  43. AuBuchon JP, Birmeyer JD, Busch MP . Safety of the blood supply in the United States: opportunities and controversies. Ann Intern Med 1997; 127: 904–909.

    Article  CAS  Google Scholar 

  44. Dodd RY, Notari EP . Current prevalence and incidence of infectious disease markers and estimated window-period risk in the American Red Cross blood donor population. Transfusion 2002; 42: 975–979.

    Article  CAS  Google Scholar 

  45. Murphy WG . Disease transmission by blood products: past, present and future. Pathophysiol Haemost Thromb 2002; 32: 1–4.

    Article  CAS  Google Scholar 

  46. Schreiber GB, Busch MP, Kleinman SH, Korelitz JJ . The risk of transfusion-transmitted viral infections. N Engl J Med 1996; 334: 1685–1690.

    Article  CAS  Google Scholar 

  47. Pealer LN, Marfin AA, Petersen LR et al. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med 2003; 349: 1236–1245.

    Article  CAS  Google Scholar 

  48. Dodd RY . Bacterial contamination and transfusion safety: experience in the United States. Transfus Clin Biol 2003; 10: 6–9.

    Article  Google Scholar 

  49. Abulrahi HA, Bohlega EA, Fontaine RE . Plasmodium falciparum malaria transmitted in hospital through heparin locks. Lancet 1997; 349: 23–25.

    Article  CAS  Google Scholar 

  50. Coles AJ, Wing M, Smith S et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet 1999; 354: 1691–1695.

    Article  CAS  Google Scholar 

  51. Van Laar JM, Tyndall A . Intense immunosuppression and stem-cell transplantation for patients with severe rheumatic autoimmune disease: a review. Cancer Control 2003; 10: 57–65 (Review).

    Article  Google Scholar 

  52. Trendelenburg M, Gregor M, Passweg J et al. ‘Altered immunity syndrome’, a distinct entity in long-term bone marrow transplantation survivors? Bone Marrow Transplant 2001; 28: 1175–1176.

    Article  CAS  Google Scholar 

  53. Tyndall A, Matucci-Cerinic M . Haematopoietic stem cell transplantation for the treatment of systemic sclerosis and other autoimmune disorders. Expert Opin Biol Ther 2003; 3: 1041–1049.

    Article  Google Scholar 

  54. McKendry RJ, Huebsch L, Leclair B . Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13-year follow-up. Arthritis Rheum 1996; 39: 1246–1253.

    Article  CAS  Google Scholar 

  55. Berg KD, Brinster NK, Huhn KM et al. Transmission of a T-cell lymphoma by allogeneic bone marrow transplantation. N Engl J Med 2001; 345: 1458–1463.

    Article  CAS  Google Scholar 

  56. Kiss TJ, Chang H, Daly A et al. Bone marrow aspirates as part of routine donor assessment for allogeneic blood and marrow transplantation can reveal presence of occult hematological malignancies in otherwise asymptomatic individuals. Bone Marrow Transplant 2004; 33: 855–858.

    Article  CAS  Google Scholar 

  57. Healey PJ, Davis CJ . Transmission of tumours by transplantation. Lancet 1998; 352: 2–3.

    Article  CAS  Google Scholar 

  58. Kauffman HM, McBride MA, Cherikh WS et al. Transplant tumor registry: donors with central nervous system tumors. Transplantation 2002; 73: 579–582.

    Article  Google Scholar 

  59. Schenkein DP, Schwartz RS . Neoplasms and transplantation – trading swords for plowshares. N Engl J Med 1997; 336: 949–950.

    Article  CAS  Google Scholar 

  60. Bodo I, Peters M, Radich JP et al. Donor-derived acute promyelocytic leukemia in a liver-transplant recipient. N Engl J Med 1999; 341: 807–813.

    Article  CAS  Google Scholar 

  61. Cleaver SA, Warren P, Kern M et al. Donor work-up and transport of bone marrow – recommendations and requirements for a standardized practice throughout the world from the Donor Registries and Quality Assurance Working Groups of the World Marrow Donor Association (WMDA). Bone Marrow Transplant 1997; 20: 621–629.

    Article  CAS  Google Scholar 

  62. Shpilberg O, Modan M, Modan B et al. Familial aggregation of nonhematological malignancies in relatives of patients with hematological neoplasms. Br J Haematol 1994; 87: 75–80.

    Article  CAS  Google Scholar 

  63. Grosbois B, Jego P, Attal M et al. Familial multiple myeloma: report of fifteen families. Br J Haematol 1999; 105: 768–770.

    Article  CAS  Google Scholar 

  64. Mandla SG, Goobie S, Kumar RT et al. Genetic analysis of familial myelodysplastic syndrome: absence of linkage to chromosomes 5q31 and 7q22. Cancer Genet Cytogenet 1998; 105: 113–118.

    Article  CAS  Google Scholar 

  65. Paltiel O, Schmit T, Adler B et al. The incidence of lymphoma in first degree relatives of patients with Hodgkin's disease and non Hodgkin's lymphoma: results and limitations of a registry linked study. Cancer 2000; 88: 2357–2366.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work is supported in part by European Community Framework 6 European Network and the German Network Leukämie.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D Niederwieser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niederwieser, D., Gentilini, C., Hegenbart, U. et al. Transmission of donor illness by stem cell transplantation: should screening be different in older donors?. Bone Marrow Transplant 34, 657–665 (2004). https://doi.org/10.1038/sj.bmt.1704588

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704588

Keywords

Search

Quick links