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Post-Transplant Events

Comparable incidence and severity of cytomegalovirus infections following T cell-depleted allogeneic stem cell transplantation preceded by reduced intensity or myeloablative conditioning

Abstract

Reports on infectious complications following reduced intensity conditioning (RIC) before allogeneic stem cell transplantation (allo-SCT) are equivocal. This prospective follow-up study compared the impact of cytomegalovirus (CMV) infections following RIC with fludarabine, ATG and busulphan or conventional myeloablative conditioning (MAC). Forty-eight RIC and 59 MAC patients were enrolled. The occurrence and severity of CMV infections within 100 days following allo-SCT were assessed, using plasma CMV DNA load kinetics. CMV DNAemia was observed in 21 RIC (60%) and in 19 MAC (44%) patients at risk for CMV. The mean CMV DNAemia free survival time was comparable following RIC and MAC: 70 days (95% (confidence interval) CI: 59–80 days) and 77 days (95% CI: 68–86 days), respectively (P=0.24). Parameters indicative for the level of CMV reactivation, including the area under the curve of CMV DNA load over time as well as the onset, the peak values and duration of CMV infection episodes, the numbers and duration of CMV treatment episodes and recurrent infections, were not different in both groups. During follow-up, none of the patients developed CMV disease. RIC with fludarabine, ATG and busulphan demonstrated safety comparable to conventional MAC with regard to frequency and severity of CMV infections within 100 days following T cell-depleted allo-SCT.

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References

  1. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  2. Khouri IF, Keating M, Korbling M, Przepiorka D, Anderlini P, O'Brien S 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. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  PubMed  Google Scholar 

  3. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G 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  PubMed  Google Scholar 

  4. Barge RM, Osanto S, Marijt WA, Starrenburg CW, Fibbe WE, Nortier JW et al. Minimal GVHD following in-vitro T cell-depleted allogeneic stem cell transplantation with reduced-intensity conditioning allowing subsequent infusions of donor lymphocytes in patients with hematological malignancies and solid tumors. Exp Hematol 2003; 31: 865–872.

    Article  CAS  PubMed  Google Scholar 

  5. Junghanss C, Marr KA . Infectious risks and outcomes after stem cell transplantation: are nonmyeloablative transplants changing the picture? Curr Opin Infect Dis 2002; 15: 347–353.

    Article  PubMed  Google Scholar 

  6. Ljungman P, Reusser P, de la CR, Einsele H, Engelhard D, Ribaud P et al. Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant 2004; 33: 1075–1081.

    Article  CAS  PubMed  Google Scholar 

  7. Ljungman P . Beta-herpesvirus challenges in the transplant recipient. J Infect Dis 2002; 186: S99–S109.

    Article  PubMed  Google Scholar 

  8. Crumpacker CS . Ganciclovir. N Engl J Med 1996; 335: 721–729.

    Article  CAS  PubMed  Google Scholar 

  9. Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD . Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355: 2032–2036.

    Article  CAS  PubMed  Google Scholar 

  10. Schafer P, Tenschert W, Cremaschi L, Schroter M, Zollner B, Laufs R . Area under the viraemia curve versus absolute viral load: utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients. J Med Virol 2001; 65: 85–89.

    Article  CAS  PubMed  Google Scholar 

  11. Barge RM, Brouwer RE, Beersma MF, Starrenburg CW, Zwinderman AH, Hale G et al. Comparison of allogeneic T cell-depleted peripheral blood stem cell and bone marrow transplantation: effect of stem cell source on short- and long-term outcome. Bone Marrow Transplant 2001; 27: 1053–1058.

    Article  CAS  PubMed  Google Scholar 

  12. 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 HLA-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  13. 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 Seattle patients. Am J Med 20; 69: 204–217.

    Article  Google Scholar 

  14. Kalpoe JS, Kroes AC, de Jong MD, Schinkel J, de Brouwer CS, Beersma MF et al. Validation of clinical application of cytomegalovirus plasma DNA load measurement and definition of treatment criteria by analysis of correlation to antigen detection. J Clin Microbiol 2004; 42: 1498–1504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Journot V, Chene G, Joly P, Saves M, Jacqmin-Gadda H, Molina JM et al. Viral load as a primary outcome in human immunodeficiency virus trials: a review of statistical analysis methods. Control Clin Trials 2001; 22: 639–658.

    Article  CAS  PubMed  Google Scholar 

  16. Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B et al. Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2004; 4: 611–620.

    Article  CAS  PubMed  Google Scholar 

  17. Ljungman P, Griffiths P, Paya C . Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34: 1094–1097.

    Article  PubMed  Google Scholar 

  18. Mackinnon S, Thomson K, Morris E, Kottaridis PD, Peggs KS . Reduced intensity transplantation: where are we now? Hematol J 2004; 5: S34–S38.

    Article  PubMed  Google Scholar 

  19. Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J . Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant 2003; 9: 543–558.

    Article  PubMed  Google Scholar 

  20. Junghanss C, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood 2002; 99: 1978–1985.

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. Nachbaur D, Larcher C, Kircher B, Eibl G, Nussbaumer W, Gunsilius E et al. Risk for cytomegalovirus infection following reduced intensity allogeneic stem cell transplantation. Ann Hematol 2003; 82: 621–627.

    Article  PubMed  Google Scholar 

  23. Schetelig J, Oswald O, Steuer N, Radonic A, Thulke S, Held TK et al. Cytomegalovirus infections in allogeneic stem cell recipients after reduced-intensity or myeloablative conditioning assessed by quantitative PCR and pp65-antigenemia. Bone Marrow Transplant 2003; 32: 695–701.

    Article  CAS  PubMed  Google Scholar 

  24. Boeckh M, Nichols WG . The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004; 103: 2003–2008.

    Article  CAS  PubMed  Google Scholar 

  25. Ljungman P, Perez-Bercoff L, Jonsson J, Avetisyan G, Sparrelid E, Aschan J et al. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica 2006; 91: 78–83.

    PubMed  Google Scholar 

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Correspondence to J S Kalpoe.

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Kalpoe, J., van der Heiden, P., Vaessen, N. et al. Comparable incidence and severity of cytomegalovirus infections following T cell-depleted allogeneic stem cell transplantation preceded by reduced intensity or myeloablative conditioning. Bone Marrow Transplant 40, 137–143 (2007). https://doi.org/10.1038/sj.bmt.1705701

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