Abstract
Hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning (NMSCT) may be associated with a reduced risk of infection compared to standard allogeneic HCT. We retrospectively analyzed incidence and risk factors of infection in 62 patients undergoing NMSCT with low-dose TBI +/− fludarabine and postgrafting CsA and MMF. The proportion of patients with any infection was 77%, but the majority of infectious events occurred beyond day 30. Donor other than sibling, older age, early disease and male gender were significant risk factors. The incidence of bacteremia was 55% at 1 year and the number of bacteremic episodes was 0.9 per patient (0.08 before day 30). The risk of bacteremia increased with older age and the use of a donor other than an HLA-identical sibling, but not with neutropenia. The incidence of infections other than bacteremia correlated with the use of corticosteroids. The risk of CMV infection increased with high-risk CMV serology, and risk of CMV disease with high-risk CMV serology, older age, first transplantation and a diagnosis of lymphoma. In conclusion, after NMSCT, infections are not frequent in the first 30 days post transplant but careful long-term monitoring is necessary thereafter.
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References
Storb R . Allogeneic hematopoietic stem cell transplantation – yesterday, today, and tomorrow. Exp Hematol 2003; 31: 1–10.
Slavin S, Morecki S, Weiss L, Shapira MY, Resnick I, Or R . Nonmyeloablative stem cell transplantation: reduced-intensity conditioning for cancer immunotherapy – from bench to patient bedside. Semin Oncol 2004; 31: 4–21.
Baron F, Beguin Y . Nonmyeloablative allogeneic hematopoietic stem cell transplantation. J Hematother Stem Cell Res 2002; 11: 243–263.
McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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.
Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM 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.
McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications. Biol Blood Marrow Transplant 1999; 5: 192–203.
Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.
Hughes WT, Armstrong D, Bodey GP, Brown AE, Edwards JE, Feld R et al. 1997 guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. Infectious Diseases Society of America. Clin Infect Dis 1997; 25: 551–573.
Junghanss C, Marr KA, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Incidence and outcome of bacterial and fungal infections following nonmyeloablative compared with myeloablative allogeneic hematopoietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 2002; 8: 512–520.
Martino R, Caballero MD, Canals C, San Miguel J, 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.
Mossad SB, Avery RK, Longworth DL, Kuczkowski EM, McBee M, Pohlman BL et al. Infectious complications within the first year after nonmyeloablative allogeneic peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 28: 491–495.
Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 2003; 102: 827–833.
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.
Baron F, Schaaf-Lafontaine N, Humblet-Baron S, Meuris N, Castermans E, Baudoux E et al. T-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation. Transplantation 2003; 76: 1705–1713.
Hori A, Kami M, Kim SW, Chizuka A, Kojima R, Imataki O et al. Development of early neutropenic fever, with or without bacterial infection, is still a significant complication after reduced-intensity stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 65–72.
Hagen EA, Stern H, Porter D, Duffy K, Foley K, Luger S et al. High rate of invasive fungal infections following nonmyeloablative allogeneic transplantation. Clin Infect Dis 2003; 36: 9–15.
Daly A, McAfee S, Dey B, Colby C, Schulte L, Yeap B et al. Nonmyeloablative bone marrow transplantation: infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant 2003; 9: 373–382.
Mohty M, Faucher C, Vey N, Stoppa AM, Viret F, Chabbert I et al. High rate of secondary viral and bacterial infections in patients undergoing allogeneic bone marrow mini-transplantation. Bone Marrow Transplant 2000; 26: 251–255.
Feinstein L, Sandmaier B, Maloney D, McSweeney PA, Maris M, Flowers C et al. Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect. Ann NY Acad Sci 2001; 938: 328–337.
Baron F, Baudoux E, Frere P, Tourqui S, Schaaf-Lafontaine N, Greimers R et al. Nonmyeloablative stem cell transplantation with CD8-depleted or CD34-selected peripheral blood stem cells. J Hematother Stem Cell Res 2002; 11: 301–314.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.
Cordonnier C, Engelhard D, Ljungman P, Dekker A, Donnelly JP, Einsele H et al. Definitions of infectious diseases and complications after stem cell transplant. In: Web site of the EBMT 2001.
Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis 2002; 34: 7–14.
Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.
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.
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.
Ninin E, Milpied N, Moreau P, Andre-Richet B, Morineau N, Mahe B et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis 2001; 33: 41–47.
Frere P, Hermanne JP, Debouge MH, De Mol P, Fillet G, Beguin Y . Bacteremia after hematopoietic stem cell transplantation: incidence and predictive value of surveillance cultures. Bone Marrow Transplant 2004; 33: 745–749.
Frere P, Hermanne JP, Debouge MH, Fillet G, Beguin Y . Changing pattern of bacterial susceptibility to antibiotics in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2002; 29: 589–594.
Yuen KY, Woo PC, Hui CH, Luk WK, Chen FE, Lie AK et al. Unique risk factors for bacteraemia in allogeneic bone marrow transplant recipients before and after engraftment. Bone Marrow Transplant 1998; 21: 1137–1143.
Marr KA, Carter RA, Boeckh M, Martin P, Corey L . Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 2002; 100: 4358–4366.
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.
Nakamura R, Cortez K, Solomon S, Battiwalla M, Gill VJ, Hensel N et al. High-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant 2002; 30: 235–242.
Maris M, Boeckh M, Storer B, Dawson M, White K, Keng M et al. Immunologic recovery after hematopoietic cell transplantation with nonmyeloablative conditioning. Exp Hematol 2003; 31: 941–952.
Bainton RD, Byrne JL, Davy BJ, Russell NH . CMV infection following nonmyeloablative allogeneic stem cell transplantation using Campath. Blood 2002; 100: 3843–3844.
Hambach L, Stadler M, Dammann E, Ganser A, Hertenstein B . Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant 2002; 29: 903–906.
Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood 2003; 101: 407–414.
Acknowledgements
Frédéric Baron is Research Associate and Yves Beguin Research Director of the National Fund for Scientific Research (FNRS, Belgium). This work was supported by grants from ‘La Fondation Frédéricq,’ ‘L’Association sportive contre le Cancer,’ ‘Le Fonds de Recherche Scientifique du CHU Sart-Tilman’ and the National Fund for Scientific Research (FNRS, Belgium). We are grateful to the medical nursing and clinical staffs for their dedicated care of the patients. We also thank Laurence Seidel and Adelin Albert from the Department of Medical Statistics for their valuable help in statistical analyses.
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Frère, P., Baron, F., Bonnet, C. et al. Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen. Bone Marrow Transplant 37, 411–418 (2006). https://doi.org/10.1038/sj.bmt.1705255
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DOI: https://doi.org/10.1038/sj.bmt.1705255
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