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Post-Transplant Events

Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution

Bone Marrow Transplantation volume 46, pages 690–701 (2011)Cite this article

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Abstract

Infection-related mortality (IRM) is responsible for a major proportion of all cases of non-relapse mortality (NRM) after allogeneic PBSCT (alloPBSCT). We analyzed 580 consecutive adults who received a first alloPBSCT from an HLA-identical sibling from 1994 to 2008 at a single institution to describe the severe infections and report the incidence, causes and risk factors for IRM and NRM. Both IRM and NRM decreased with time; within the period of 1994–2000, the 2-year incidence of IRM and NRM was 22 and 31%, respectively, vs 11 and 16% within the period of 2001–2008 (P<0.05 for both comparisons). In multivariate analysis, the variables that increased IRM were within the earlier period of 1994–2000 (P<0.01), poor performance status (P<0.01), grade II–IV acute GVHD (P<0.001) and invasive fungal infection (IFI) (P<0.001) or CMV disease (P<0.001) after transplant. With respect to NRM, earlier time period was also identified as a risk factor (P<0.001), as well as IFIs (P<0.001) and CMV disease (P<0.001). The intensity of the conditioning regimen had no effect on IRM and NRM. These results showed a significant reduction in IRM and NRM over a period of 15 years. The development of IFIs and CMV disease continue to have an impact on NRM.

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References

  1. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15: 1143–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Frassoni F, Labopin M, Powles R, Mary JY, Arcese W, Bacigalupo A et al. Effect of centre on outcome of bone-marrow transplantation for acute myeloid leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 2000; 355: 1393–1398.

    Article  CAS  PubMed  Google Scholar 

  3. Gratwohl A, Brand R, Frassoni F, Rocha V, Niederwieser D, Reusser P et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplant 2005; 36: 757–769.

    Article  CAS  PubMed  Google Scholar 

  4. Przepiorka D, Smith TL, Folloder J, Khouri I, Ueno NT, Mehra R et al. Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 1999; 94: 1465–1470.

    CAS  PubMed  Google Scholar 

  5. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  6. Martino R, Caballero MD, Canals C, Simon JA, Solano C, Urbano-Ispizua A et al. Allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results of a prospective multicentre study. Br J Haematol 2001; 115: 653–659.

    Article  CAS  PubMed  Google Scholar 

  7. Martino R, Valcarcel D, Brunet S, Sureda A, Sierra J . Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant 2008; 41: 33–38.

    Article  CAS  PubMed  Google Scholar 

  8. Martino R, Rovira M, Carreras E, Solano C, Jorge S, De La RJ et al. Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD34+ cell-selected transplantation. Haematologica 2001; 86: 1075–1086.

    CAS  PubMed  Google Scholar 

  9. Urbano-Ispizua A, Rozman C, Pimentel P, Solano C, de la RJ, Brunet S et al. The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings. Blood 2001; 97: 383–387.

    Article  CAS  PubMed  Google Scholar 

  10. Martino R, Bretagne S, Einsele H, Maertens J, Ullmann AJ, Parody R et al. Early detection of Toxoplasma infection by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplantation. Clin Infect Dis 2005; 40: 67–78.

    Article  PubMed  Google Scholar 

  11. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Martino R, Caballero MD, Canals C, San MJ, Sierra J, Rovira M et al. Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 341–347.

    Article  CAS  PubMed  Google Scholar 

  13. Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica 2004; 89: 1238–1247.

    PubMed  Google Scholar 

  14. Cantoni N, Weisser M, Buser A, Arber C, Stern M, Heim D et al. Infection prevention strategies in a stem cell transplant unit: impact of change of care in isolation practice and routine use of high dose intravenous immunoglobulins on infectious complications and transplant related mortality. Eur J Haematol 2009; 83: 130–138.

    Article  CAS  PubMed  Google Scholar 

  15. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de WT et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer 2009; 115: 4715–4726.

    Article  PubMed  Google Scholar 

  16. Gahrton G, Svensson H, Cavo M, Apperly J, Bacigalupo A, Bjorkstrand B et al. Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: a comparison between transplants performed 1983–93 and 1994–8 at European Group for Blood and Marrow Transplantation centres. Br J Haematol 2001; 113: 209–216.

    Article  CAS  PubMed  Google Scholar 

  17. Blijlevens NM, Donnelly JP, DePauw BE . Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients. Bone Marrow Transplant 2005; 36: 703–707.

    Article  CAS  PubMed  Google Scholar 

  18. van d V, Blijlevens NM, Feuth T, Donnelly JP . Febrile mucositis in haematopoietic SCT recipients. Bone Marrow Transplant 2009; 43: 55–60.

    Article  Google Scholar 

  19. Martino R, Maertens J, Bretagne S, Rovira M, Deconinck E, Ullmann AJ et al. Toxoplasmosis after hematopoietic stem cell transplantation. Clin Infect Dis 2000; 31: 1188–1195.

    Article  CAS  PubMed  Google Scholar 

  20. Boeckh M, Kim HW, Flowers ME, Meyers JD, Bowden RA . Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation—a randomized double-blind placebo-controlled study. Blood 2006; 107: 1800–1805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Parody R, Martino R, Rovira M, Vazquez L, Vazquez MJ, de la CR et al. Severe infections after unrelated donor allogeneic hematopoietic stem cell transplantation in adults: comparison of cord blood transplantation with peripheral blood and bone marrow transplantation. Biol Blood Marrow Transplant 2006; 12: 734–748.

    Article  PubMed  Google Scholar 

  22. Safdar A, Rodriguez GH, Mihu CN, Mora-Ramos L, Mulanovich V, Chemaly RF et al. Infections in non-myeloablative hematopoietic stem cell transplantation patients with lymphoid malignancies: spectrum of infections, predictors of outcome and proposed guidelines for fungal infection prevention. Bone Marrow Transplant 2010; 45: 339–347.

    Article  CAS  PubMed  Google Scholar 

  23. Martino R, Subira M, Rovira M, Solano C, Vazquez L, Sanz GF et al. Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients. Br J Haematol 2002; 116: 475–482.

    Article  PubMed  Google Scholar 

  24. Perez-Simon JA, ez-Campelo M, Martino R, Sureda A, Caballero D, Canizo C et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced-intensity-conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102: 1108–1113.

    Article  CAS  PubMed  Google Scholar 

  25. Urbano-Ispizua A . High stem cell dose in haemopoietic transplantation: is it always beneficial? Leukemia 2003; 17: 1467–1469.

    Article  CAS  PubMed  Google Scholar 

  26. Mohty M, Bilger K, Jourdan E, Kuentz M, Michallet M, Bourhis JH et al. Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation. Leukemia 2003; 17: 869–875.

    Article  CAS  PubMed  Google Scholar 

  27. Zaucha JM, Gooley T, Bensinger WI, Heimfeld S, Chauncey TR, Zaucha R et al. CD34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen-identical sibling transplantation. Blood 2001; 98: 3221–3227.

    Article  CAS  PubMed  Google Scholar 

  28. Mehta J, Frankfurt O, Altman J, Evens A, Tallman M, Gordon L et al. Optimizing the CD34 + cell dose for reduced-intensity allogeneic hematopoietic stem cell transplantation. Leuk Lymphoma 2009; 50: 1434–1441.

    Article  PubMed  Google Scholar 

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Author notes

  1. R Martino and A Kerguelen: These authors contributed equally to this study and to the preparation of this paper, and should be considered as first co-authors.

Authors and Affiliations

  1. Department of Hematology and Stem Cell Transplantation, Hospital de la Sant Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    R Martino, A Kerguelen, D Valcárcel, A Sureda, L Fachini, J L Piñana, J Briones, J Delgado, S Brunet & J Sierra

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  1. R Martino
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Correspondence to R Martino.

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Martino, R., Kerguelen, A., Valcárcel, D. et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant 46, 690–701 (2011). https://doi.org/10.1038/bmt.2010.177

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