Seminars in Hematology
Volume 49, Issue 1 , Pages 10-14 , January 2012

Challenges to Preventing Infectious Complications, Decreasing Re-hospitalizations, and Reducing Cost Burden in Long-Term Survivors After Allogeneic Hematopoietic Stem Cell Transplantation

  • Shigeo Fuji
  • ,
  • Markus Kapp
  • ,
  • Hermann Einsele

      Affiliations

    • Corresponding Author InformationAddress correspondence to Hermann Einsele, MD, Department of Internal Medicine II, Division of Hematology, University Hospital of Würzburg, Josef-Schneider-Straße 2, 97080 Würzburg, Germany

References 

  1. Gooley TA , Chien JW , Pergam SA , et al.  Reduced mortality after allogeneic hematopoietic-cell transplantation . N Engl J Med . 2010;363:2091–2101
  2. Horan JT , Logan BR , Agovi-Johnson MA , et al.  Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? . J Clin Oncol . 2011;29:805–813
  3. Savani BN , Griffith ML , Jagasia S , Lee SJ . How I treat late effects in adults after allogeneic stem cell transplantation . Blood . 2011;117:3002–3009
  4. Martin PJ , Counts GW , Appelbaum FR , et al.  Life expectancy in patients surviving more than 5 years after hematopoietic cell transplantation . J Clin Oncol . 2010;28:1011–1016
  5. Corre E , Carmagnat M , Busson M , et al.  Long-term immune deficiency after allogeneic stem cell transplantation: B-cell deficiency is associated with late infections . Haematologica . 2010;95:1025–1029
  6. Le RQ , Melenhorst JJ , Battiwalla M , et al.  Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation . Blood . 2011;117:5250–5256
  7. Goldman JM , Majhail NS , Klein JP , et al.  Relapse and late mortality in 5-year survivors of myeloablative allogeneic hematopoietic cell transplantation for chronic myeloid leukemia in first chronic phase . J Clin Oncol . 2010;28:1888–1895
  8. Bjorklund A , Aschan J , Labopin M , et al.  Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation . Bone Marrow Transplant . 2007;40:1055–1062
  9. Robin M , Porcher R , De Castro Araujo R , et al.  Risk factors for late infections after allogeneic hematopoietic stem cell transplantation from a matched related donor . Biol Blood Marrow Transplant . 2007;13:1304–1312
  10. Rizzo JD , Wingard JR , Tichelli A , et al.  Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation . Biol Blood Marrow Transplant . 2006;12:138–151
  11. Kulkarni S , Powles R , Treleaven J , et al.  Chronic graft versus host disease is associated with long term risk for pneumococcal infections in recipients of bone marrow transplants . Blood . 2000;95:3683–3686
  12. Engelhard D , Cordonnier C , Shaw PJ , et al.  Early and late invasive pneumococcal infection following stem cell transplantation: a European Bone Marrow Transplantation survey . Br J Haematol . 2002;117:444–450
  13. Mihu CN , Schaub J , Kesh S , et al.  Risk factors for late Staphylococcus aureus bacteremia after allogeneic hematopoietic stem cell transplantation: a single-institution, nested case-controlled study . Biol Blood Marrow Transplant . 2008;14:1429–1433
  14. Cordonnier C , Labopin M , Jansen KU , et al.  Relationship between IgG titers and opsonocytophagocytic activity of anti-pneumococcal antibodies after immunization with the 7-valent conjugate vaccine in allogeneic stem cell transplant . Bone Marrow Transplant . 2010;45:1423–1426
  15. Tomblyn M , Chiller T , Einsele H , et al.  Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective . Biol Blood Marrow Transplant . 2009;15:1143–1238
  16. Engelhard D , Akova M , Boeckh MJ , et al.  Bacterial infection prevention after hematopoietic cell transplantation . Bone Marrow Transplant . 2009;44:467–470
  17. Ljungman P , Cordonnier C , Einsele H , et al.  Vaccination of hematopoietic cell transplant recipients . Bone Marrow Transplant . 2009;44:521–526
  18. Avanzini MA , Carra AM , Maccario R , et al.  Antibody response to pneumonoccal vaccine in children receiving bone marrow transplantation . J Clin Immunol . 1995;15:137–144
  19. Cordonnier C , Labopin M , Chesnel V . Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: results from the EBMT IDWP01 trial . Vaccine . 2010;28:2730–2734
  20. Parkkali T , Stenvik M , Ruutu T , Hovi T , Volin L , Ruutu P . Randomized comparison of early and late vaccination with inactivated poliovirus vaccine after allogeneic BMT . Bone Marrow Transplant . 1997;20:663–668
  21. Parkkali T , Olander RM , Ruutu T , et al.  A randomized comparison between early and late vaccination with tetanus toxoid vaccine after allogeneic BMT . Bone Marrow Transplant . 1997;19:933–938
  22. Parkkali T , Käyhty H , Ruutu T , Volin L , Eskola J , Ruutu P . A comparison of early and late vaccination with Haemophilus influenzae type b conjugate and pneumococcal polysaccharide vaccines after allogeneic BMT . Bone Marrow Transplant . 1996;18:961–967
  23. Cordonnier C , Labopin M , Chesnel V , et al.  Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation . Clin Infect Dis . 2009;48:1392–1401
  24. Hilgendorf I , Freund M , Jilg W , et al.  Vaccination of allogeneic haematopoietic stem cell transplant recipients: report from the international consensus conference on clinical practice in chronic GVHD . Vaccine . 2011;29:2825–2833
  25. Meerveld-Eggink A , van der Velden AM , Ossenkoppele GJ , van de Loosdrecht AA , Biesma DH , Rijkers GT . Antibody response to polysaccharide conjugate vaccines after nonmyeloablative allogeneic stem cell transplantation . Biol Blood Marrow Transplant . 2009;15:1523–1530
  26. Parkkali T , Käyhty H , Hovi T , et al.  A randomized study on donor immunization with tetanus-diphtheria, Haemophilus influenzae type b and inactivated poliovirus vaccines to improve the recipient responses to the same vaccines after allogeneic bone marrow transplantation . Bone Marrow Transplant . 2007;39:179–188
  27. Molrine DC , Guinan EC , Antin JH , et al.  Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation . Blood . 1996;87:3012–3018
  28. 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
  29. Jantunen E , Ruutu P , Niskanen L , et al.  Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients . Bone Marrow Transplant . 1997;19:801–808
  30. Mikulska M , Raiola AM , Bruno B , et al.  Risk factors for invasive aspergillosis and related mortality in recipients of allogeneic SCT from alternative donors: an analysis of 306 patients . Bone Marrow Transplant . 2009;44:361–370
  31. Maertens J , Marchetti O , Herbrecht R , et al.  Third European Conference on Infections in Leukemia (European guidelines for antifungal management in leukemia and hematopoietic stem cell transplant recipients: summary of the ECIL 3—2009 update) . Bone Marrow Transplant . 2011;46:709–718
  32. Ullmann AJ , Lipton JH , Vesole DH , et al.  Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease . N Engl J Med . 2007;356:335–347
  33. Garcia-Vidal C , Upton A , Kirby KA , Marr KA . Epidemiology of invasive mold infections in allogeneic stem cell transplant recipients: biological risk factors for infection according to time after transplantation . Clin Infect Dis . 2008;47:1041–1050
  34. McKay PJ , Murphy JA , Cameron S , et al.  Iron overload and liver dysfunction after allogeneic or autologous bone marrow transplantation . Bone Marrow Transplant . 1996;17:63–66
  35. Sucak GT , Yegin ZA , Ozkurt ZN , Aki SZ , Karakan T , Akyol G . The role of liver biopsy in the workup of liver dysfunction late after SCT:is the role of iron overload underestimated? . Bone Marrow Transplant . 2008;42:461–467
  36. Altes A , Remacha AF , Sarda P , et al.  Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis . Bone Marrow Transplant . 2004;34:505–509
  37. Majhail NS , DeFor T , Lazarus HM , Burns LJ . High prevalence of iron overload in adult allogeneic hematopoietic cell transplant survivors . Biol Blood Marrow Transplant . 2008;14:790–794
  38. Kontoghiorghes GJ , Kolnagou A , Skiada A , Petrikkos G . The role of iron and chelators on infections in iron overload and non iron loaded conditions: prospects for the design of new antimicrobial therapies . Hemoglobin . 2010;34:227–239
  39. Pullarkat V . Objectives of iron chelation therapy in myelodysplastic syndromes: more than meets the eye? . Blood . 2009;114:5251–5255
  40. Asano-Mori Y , Kanda Y , Oshima K , et al.  Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation . Int J Hematol . 2008;87:310–318
  41. Hebart H , Daginik S , Stevanovic S , et al.  Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T-lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation . Blood . 2002;99:3830–3837
  42. Gratama JW , van Esser JW , Lamers CH , et al.  Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection . Blood . 2001;98:1358–1364
  43. Ganepola S , Gentilini C , Hilbers U , et al.  Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation . Bone Marrow Transplant . 2007;39:293–299
  44. Boeckh M , Leisenring W , Riddell SR , 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
  45. Zhou W , Longmate J , Lacey SF , et al.  Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients . Blood . 2009;113:6465–6476
  46. Pietersma FL , van Dorp S , Minnema MC , et al.  Influence of donor cytomegalovirus (CMV) status on severity of viral reactivation after allogeneic stem cell transplantation in CMV-seropositive recipients . Clin Infect Dis . 2011;52:e144–e148
  47. Herr W , Plachter B . Cytomegalovirus and varicella-zoster virus vaccines in hematopoietic stem cell transplantation . Expert Rev Vaccines . 2009;8:999–1021
  48. Griffiths PD , Stanton A , McCarrell E , et al.  Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial . Lancet . 2011;377:1256–1263
  49. Pass RF , Zhang C , Evans A , et al.  Vaccine prevention of maternal cytomegalovirus infection . N Engl J Med . 2009;360:1191–1199
  50. Wang Z , La Rosa C , Maas R , et al.  Recombinant modified vaccinia virus Ankara expressing a soluble form of glycoprotein B causes durable immunity and neutralizing antibodies against multiple strains of human cytomegalovirus . J Virol . 2004;78:3965–3976
  51. Flechsig C , Suezer Y , Kapp M , et al.  Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells . Cytotherapy . 2011;13:739–752
  52. Erard V , Guthrie KA , Varley C , et al.  One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation . Blood . 2007;110:3071–3077
  53. 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
  54. Chou JF , Kernan NA , Prockop S , et al.  Safety and immunogenicity of the live attenuated varicella vaccine following T replete or T cell-depleted related and unrelated allogeneic hematopoietic cell transplantation (alloHCT) . Biol Blood Marrow Transplant . 2011;17:1708–1713
  55. Kussmaul SC , Horn BN , Dvorak CC , Abramovitz L , Cowan MJ , Weintrub PS . Safety of the live, attenuated varicella vaccine in pediatric recipients of hematopoietic SCTs . Bone Marrow Transplant . 2010;45:1602–1606
  56. Mohty B , Bel M , Vukicevic M , et al.  Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients . Haematologica . 2011;96:896–904
  57. de Lavallade H , Garland P , Sekine T , et al.  Repeated vaccination is required to optimize seroprotection against H1N1 in the immunocompromised host . Haematologica . 2011;96:307–314
  58. Issa NC , Marty FM , Gagne LS , et al.  Seroprotective titers against 2009 H1N1 influenza A virus after vaccination in allogeneic hematopoietic stem cell transplantation recipients . Biol Blood Marrow Transplant . 2011;17:434–438
  59. Avetisyan G , Aschan J , Hassan M , Ljungman P . Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation . Transplantation . 2008;86:257–263
  60. Ferguson PE , Jordens CF , Gilroy NM . Patient and family education in HSCT: improving awareness of respiratory virus infection and influenza vaccination (A descriptive study and brief intervention) . Bone Marrow Transplant . 2010;45:656–661

 The authors have no conflicts of interest to declare.

PII: S0037-1963(11)00103-X

doi: 10.1053/j.seminhematol.2011.10.009

Seminars in Hematology
Volume 49, Issue 1 , Pages 10-14 , January 2012