Skip to main content

Advertisement

SpringerLink
Log in

Risk for cytomegalovirus infection following reduced intensity allogeneic stem cell transplantation

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Preliminary data suggest a faster immune recovery following non-myeloablative stem cell transplantation because of the persistence of recipient T cells, but the real impact on post-transplant infectious complications remains unknown. We retrospectively analysed the incidence of cytomegalovirus (CMV) infection in twenty patients following reduced intensity conditioning with busulfan/fludarabine±thiotepa and post-transplant immunosuppression with cyclosporine A/mycophenolate mofetil. Results were compared with 20 patients receiving myeloablative transplants during the same time period and who were matched for CMV risk group and for donor origin. The cumulative incidence of CMV infection following reduced intensity vs. myeloablative transplants was 60.4% vs. 40.0%, respectively (p value 0.1, log rank test). The risk for CMV infection in both cohorts was increased after in vivo T cell depletion with antithymocyte globulin (75% and 60%, respectively). Acute GVHD preceded the diagnosis of CMV infection by a median of 25 (range, 9–61) days following reduced intensity transplants and a median of 14 (range, 10–34) days in myeloablative transplants. Recurrent CMV infections were observed only in patients receiving reduced intensity transplants. Using multivariate analysis only reduced intensity transplantation and in vivo T cell depletion had a significant impact on the risk of CMV infection. In our series the incidence for CMV infection following reduced intensity transplants seems to be increased as compared with risk-matched myeloablative transplants. When adding anti-T cell antibodies to the conditioning regimen, the risk for CMV infection increases by up to 75%. Thorough studies of the risk of post-transplant viral infection are necessary to optimize surveillance as well as pre-emptive and/or prophylactic treatment strategies in the non-myeloablative transplantation setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2a, b.

Similar content being viewed by others

References

  1. Bregni M, Dodero A, Peccatori J, Pescarollo A, Bernardi M, Sassi I, Voena C, Zaniboni A, Bardignon C, Corradini P (2002) Nonmyeloablative conditioning followed by hematopietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 99:4234–4236

    Article  CAS  PubMed  Google Scholar 

  2. Carella AM, Champlin R, Slavin S, McSweeney, Storb R (2000) Mini-allografts: ongoing trials in humans. Bone Marrow Transplant 25:345–350

    Article  CAS  PubMed  Google Scholar 

  3. Carella AM, Beltrami G, Carella M Jr, Corsetti MT, Scalzulli RP, Greco M (2001) Immunosuppressive non-myeloablative allografting as salvage therapy in advanced Hodgkin's disease. Haematologica 86:1121–1123

    CAS  PubMed  Google Scholar 

  4. Chakrabarti S, Mackinnon S, Chopra R, Kottardis PD, Peggs K, O'Gorman P, Chakraverty R, Marshall T, Osman H, Mahendra P, Craddock C, Waldmann H, Hale G, Fegan CD, Yong K, Goldstone AH, Linch DC, Milligan DW (2002) High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution. Blood 99:4357–4363

    Article  CAS  PubMed  Google Scholar 

  5. Feinstein L, Sandmaier B, Maloney D, McSweeney PA, Maris M, Flowers C, Radich J, Little MT, Nash RA, Chauncey T, Woolfrey A, Georges G, Kiem HP, Zaucha JM, Blume KG, Shizuru J, Niederwieser D, Storb R (2001) Nonmyeloablative hematopoietic stem cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann N Y Acad Sci 938:328–337

    CAS  PubMed  Google Scholar 

  6. Finke J, Bertz H, Schmoor C, Veelken H, Behringer D, Wäsch R, Kunzmann R, Heidecker L, Lang H, Meyer-König U, Mertelsmann R (2000) Allogeneic bone marrow transplantation from unrelated donors using in vivo anti-T cell globulin. Br J Haematol 111:303–313

    Article  CAS  Google Scholar 

  7. Friedman TM, Varadi G, Hopely DD, Filicko J, Wagner J, Ferber A, Martinez J, Brunner J, Grosso D, Mcguire L, Korngold R, Flomenberg N (2001) Nonmyeloablative conditioning allows for more rapid T cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches. Biol Blood Marrow Transplant 7:656–664

    CAS  PubMed  Google Scholar 

  8. Gaiger A, Mannhalter C, Hinterberger W, Haas O, Marosi C, Kier P, Eichinger S, Lechner K (1991) Detection of engraftment and mixed chimerism following bone marrow transplantation using PCR amplification of a highly variable region-variable number of tandem repeats (VNTR) in the von Willebrand factor gene. Ann Hematol 63:227–228

    CAS  PubMed  Google Scholar 

  9. Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C, Claxton D, Donato M, Bruton J, Cohen A, Davis M, Andersson BS, Anderlini P, Gajewski, J, Kornblau S, Andreeff M, Przepiorka D, Ueno NT, Molldrem J, Champlin R (2001) Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 97:631–637

    Article  CAS  PubMed  Google Scholar 

  10. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 18:295–301

    CAS  PubMed  Google Scholar 

  11. Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representation of old estimators. Statist Med 18:695–706

    Article  CAS  Google Scholar 

  12. Hambach L, Stadler M, Dammann E, Ganser A, Hertenstein B (2002) Increased risk of complicated CMV infection with use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant 29:903–906

    Article  CAS  PubMed  Google Scholar 

  13. Hertenstein B, Hampl W, Bunjes D, Wiesneth M, Duncker C, Koszinowski U, Heimpel H, Arnold R, Mertens T (1995) In vivo/ex vivo T cell depletion for GVHD prophylaxis influences onset and course of active cytomegalovirus infection and disease after BMT. Bone Marrow Transplant 15:387–393

    CAS  PubMed  Google Scholar 

  14. Junghans C, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Chauncey T, McSweeney PA, Little MT, Corey L, Storb R (2002) Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood 99:1978–1985

    Article  PubMed  Google Scholar 

  15. Kaplan EL, Meier P (1958) Non parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Google Scholar 

  16. Khouri IF, Saliba RM, Giralt SA, Lee MS, Okoroji GJ, Hagemeister FB, Korbling M, Younes F, Ippolitti C, Gajewski JL, McLaughlin P, Anderlini P, Donato ML, Cabanillas FF, Champlin RE (2001) Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 98:3595–3599

    Article  CAS  PubMed  Google Scholar 

  17. Ljungman P, Griffths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Inf Dis 34:1094–1097

    Article  Google Scholar 

  18. Maris M, Sandmaier BM, Maloney DG, McSweeney PA, Woolfrey A, Chauncey T, Shizuru J, Niederwieser D, Blume KG, Forman S, Storb R (2001) Non-myeloablative hematopoietic stem cell transplantation. Transfus Clin Biol 8:231–234

    Article  CAS  PubMed  Google Scholar 

  19. Martino R, Caballero MD, Canals C, San Miguel J, Sierra J, Rovira M, Solano C, Bargay J, Pérez-Simon J, Léon A, Sarrá J, Brunet S, de la Cámara R, for the alloPBSCT and Infectious/Non-infectious Complications Subcommittees of the Grupo Espanol de Transplante Hematopoyético (GETH) (2001) Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 28:341–347

    Article  CAS  PubMed  Google Scholar 

  20. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG, Chauncey TR, Gooley TA, Hegenbart U, Nash RA, Radich J, Wagner JL, Minor S, Appelbaum FR, Bensinger WI, Bryant E, Flowers MED, Georges GE, Grumet FC, Kiem HP, Torok-Storb B, Yu C, Blume KG, Storb RF (2001) Hematopoietic stem cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97:3390–4000

    CAS  PubMed  Google Scholar 

  21. Mohty M, Faucher C, Vey N, Stoppa AM, Viret F, Chabbert I, Chabannon C, Bouabdallah R, Ladaique P, Collet L, Zandotti C, Maraninchi D, Blaise D (2000) High rate of secondary viral and bacterial infections in patients undergoing allogeneic bone marrow mini-transplantation. Bone Marrow Transplant 26:251–255

    Article  CAS  PubMed  Google Scholar 

  22. Morecki S, Gelfand Y, Nagler A, Or R, Naparstek E, Varadi G, Engelhard D, Akerstein A, Slavin S (2001) Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen. Bone Marrow Transplant 28:243–249

    Article  CAS  PubMed  Google Scholar 

  23. Nachbaur D, Eibl B, Kropshofer G, Meister B, Mitterschiffthaler A, Schennach H, Fischer G, Kopp M, Gunsilius E, Gastl G (2002) In vivo T cell depletion with low-dose rabbit antithymocyte globulin results in low-transplant-related mortality and low relapse incidence following unrelated hematopoietic stem cell transplantation. J Hematother Stem Cell Res 11:731–737

    Article  CAS  PubMed  Google Scholar 

  24. Savage WJ, Bleesing JJH, Douek D, Brown MR, Linton GM, Malech HL, Horwitz ME (2001) Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell transplantation follows two patterns depending on age and donor/recipient chimerism. Bone Marrow Transplant 28:463–471

    Article  CAS  PubMed  Google Scholar 

  25. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GF, Hackman R, Tsoi MS, Storb R, Thomas ED (1980) Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 69:204–211

    CAS  PubMed  Google Scholar 

  26. Storb R, Deeg HJ, Whitehead J, Applebaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V (1986) Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia. New Engl J Med 314:729–735

    CAS  PubMed  Google Scholar 

  27. Storb RF, Champlin R, Riddell SR, Murata M, Bryant S, Warren EH (2001) Non-myeloablative transplants for malignant disease. Hematology (Am Soc Hematol Educ Program) pp 375–91

Download references

Author information

Authors and Affiliations

  1. Division of Hematology & Oncology, BMT Unit, Department of Internal Medicine, Innsbruck University Hospital, Anichstrasse 35, 6020, Innsbruck, Austria

    David Nachbaur, Brigitte Kircher, Eberhard Gunsilius, Margot Haun, Kurt Grünewald & Günther Gastl

  2. Institute of Hygiene, University of Innsbruck, Innsbruck, Austria

    Clara Larcher

  3. Institute for Biostatistics and Documentation, University of Innsbruck, Innsbruck, Austria

    Günther Eibl

  4. Central Blood and Transfusion Service, Innsbruck University Hospital, Innsbruck, Austria

    Walter Nussbaumer

Authors
  1. David Nachbaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clara Larcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brigitte Kircher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Günther Eibl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Walter Nussbaumer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eberhard Gunsilius
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Margot Haun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kurt Grünewald
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Günther Gastl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Nachbaur.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nachbaur, D., Larcher, C., Kircher, B. et al. Risk for cytomegalovirus infection following reduced intensity allogeneic stem cell transplantation. Ann Hematol 82, 621–627 (2003). https://doi.org/10.1007/s00277-003-0706-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-003-0706-1

Keywords

Search

Navigation