Skip to main content

Immunotherapy for Invasive Mold Disease in Transplant Patients: Dendritic Cell Immunotherapy, Interferon Gamma, Recombinant Myeloid Growth Factors, and Healthy Donor Granulocyte Transfusions

  • Chapter
  • First Online:
  • 1504 Accesses

Abstract

Over the last half-century, there has been a steady increase in opportunistic fungal infections due to the growth in population of patients with severe and mostly iatrogenically induced immune suppression. The explosive growth of this challenge in opportunistic fungal disease has been fueled in recent decades by advances in solid organ and hematopoietic stem cell transplantation. Furthermore, use of high-dose antineoplastic chemotherapy and biologic immunosuppressive regimens in oncology and clinical practice has further escalated the risk for opportunistic infections. Systemic antifungal therapies that work relatively well within the general population are far less efficacious in patients with severe immune dysregulation. This provides an important thrust and impetus for exploring novel antifungal immune modulation strategies. Here we outline a variety of potential novel adjunct treatment paradigms in the areas of whole cell, cytokine, and small-molecule therapies that may assist in amelioration of invasive fungal disease among patients in the setting of transplantation.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Kurup VP. Interaction of Aspergillus fumigatus spores and pulmonary alveolar macrophages of rabbits. Immunobiology. 1984;166:53–61.

    Article  CAS  PubMed  Google Scholar 

  2. Bozza S, Gaziano R, Spreca A, et al. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J Immunol. 2002;168:1362–71.

    Article  CAS  PubMed  Google Scholar 

  3. Cenci E, Mencacci A, Del Sero G, et al. Interleukin-4 causes susceptibility to invasive pulmonary aspergillosis through suppression of protective type I responses. J Infect Dis. 1999;180:1957–68.

    Article  CAS  PubMed  Google Scholar 

  4. Chotirmall SH, Al-Alawi M, Mirkovic B, et al. Aspergillus-associated airway disease, inflammation, and the innate immune response. Biomed Res Int. 2013;2013:723129.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cenci E, Mencacci A, Fe d'Ostiani C, et al. Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis. 1998;178:1750–60.

    Article  CAS  PubMed  Google Scholar 

  6. Grazziutti ML, Rex JH, Cowart RE, et al. Aspergillus fumigatus conidia induce a Th1-type cytokine response. J Infect Dis. 1997;176:1579–83.

    Article  CAS  PubMed  Google Scholar 

  7. Singh N, Paterson DL. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2005;18:44–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group. Medicine. 2000;79:250–60.

    Article  CAS  PubMed  Google Scholar 

  9. Armstrong D. Infections with Pseudomonas aeruginosa, Aspergillus species and Mucoraceae. Int J Radiat Oncol Biol Phys. 1976;1:297–9.

    Article  CAS  PubMed  Google Scholar 

  10. Chamilos G, Luna M, Lewis RE, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91:986–9.

    PubMed  Google Scholar 

  11. Romani L. Cell mediated immunity to fungi: a reassessment. Med Mycol. 2008;46:515–29.

    Article  CAS  PubMed  Google Scholar 

  12. Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50:1091–100.

    Article  PubMed  Google Scholar 

  13. Pagano L, Caira M, Candoni A, et al. Invasive aspergillosis in patients with acute myeloid leukemia: a SEIFEM-2008 registry study. Haematologica. 2010;95:644–50.

    Article  PubMed  Google Scholar 

  14. Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007;45:321–46.

    Article  PubMed  Google Scholar 

  15. Tekaia F, Latge JP. Aspergillus fumigatus: saprophyte or pathogen? Curr Opin Microbiol. 2005;8:385–92.

    Article  CAS  PubMed  Google Scholar 

  16. Perea S, Patterson TF. Invasive Aspergillus infections in hematologic malignancy patients. Semin Respir Infect. 2002;17:99–105.

    Article  PubMed  Google Scholar 

  17. Steinmann J, Hamprecht A, Vehreschild MJ, et al. Emergence of azole-resistant invasive aspergillosis in HSCT recipients in Germany. J Antimicrob Chemother. 2015;70:1522–6.

    Article  CAS  PubMed  Google Scholar 

  18. Kong YC, Levine HB. Experimentally induced immunity in the mycoses. Bacteriol Rev. 1967;31:35–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 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;100:4358–66.

    Article  CAS  PubMed  Google Scholar 

  20. Grow WB, Moreb JS, Roque D, et al. Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplant. 2002;29:15–9.

    Article  CAS  PubMed  Google Scholar 

  21. Marr KA, Patterson T, Denning D. Aspergillosis. Pathogenesis, clinical manifestations, and therapy. Infect Dis Clin N Am. 2002;16:875–94.

    Article  Google Scholar 

  22. Denning DW, Follansbee SE, Scolaro M, et al. Pulmonary aspergillosis in the acquired immunodeficiency syndrome. N Engl J Med. 1991;324:654–62.

    Article  CAS  PubMed  Google Scholar 

  23. Williams DM, Weiner MH, Drutz DJ. Immunologic studies of disseminated infection with Aspergillus fumigatus in the nude mouse. J Infect Dis. 1981;143:726–33.

    Article  CAS  PubMed  Google Scholar 

  24. Roilides E, Katsifa H, Walsh TJ. Pulmonary host defences against Aspergillus fumigatus. Res Immunol. 1998;149:454–65.

    Article  CAS  PubMed  Google Scholar 

  25. Cenci E, Mencacci A, Bacci A, et al. T cell vaccination in mice with invasive pulmonary aspergillosis. J Immunol. 2000;165:381–8.

    Article  CAS  PubMed  Google Scholar 

  26. Hebart H, Bollinger C, Fisch P, et al. Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies. Blood. 2002;100:4521–8.

    Article  CAS  PubMed  Google Scholar 

  27. Fierer J, Waters C, Walls L. Both CD4+ and CD8+ T cells can mediate vaccine-induced protection against Coccidioides immitis infection in mice. J Infect Dis. 2006;193:1323–31.

    Article  CAS  PubMed  Google Scholar 

  28. Wuthrich M, Filutowicz HI, Warner T, Deepe GS Jr, Klein BS. Vaccine immunity to pathogenic fungi overcomes the requirement for CD4 help in exogenous antigen presentation to CD8+ T cells: implications for vaccine development in immune-deficient hosts. J Exp Med. 2003;197:1405–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zheng M, Ramsay AJ, Robichaux MB, et al. CD4+ T cell-independent DNA vaccination against opportunistic infections. J Clin Invest. 2005;115:3536–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bozza S, Clavaud C, Giovanni G, et al. Immune sensing of Aspergillus fumigatus proteins, glycolipids, and polysaccharides and the impact on Th immunity and vaccination. J Immunol. 2009;183:2407–14.

    Article  CAS  PubMed  Google Scholar 

  31. Bozza S, Perruccio K, Montagnoli C, et al. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood. 2003;102:3807–14.

    Article  CAS  PubMed  Google Scholar 

  32. Shao C, Qu J, He L, et al. Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis. Genes Immun. 2005;6:103–14.

    Article  CAS  PubMed  Google Scholar 

  33. Bozza S, Gaziano R, Lipford GB, et al. Vaccination of mice against invasive aspergillosis with recombinant Aspergillus proteins and CpG oligodeoxynucleotides as adjuvants. Microbes Infect. 2002;4:1281–90.

    Article  CAS  PubMed  Google Scholar 

  34. Ramirez-Ortiz ZG, Specht CA, Wang JP, et al. Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in Aspergillus fumigatus DNA. Infect Immun. 2008;76:2123–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Feldmesser M. Prospects of vaccines for invasive aspergillosis. Med Mycol. 2005;43:571–87.

    Article  CAS  PubMed  Google Scholar 

  36. Stevens DA, Clemons KV, Liu M. Developing a vaccine against aspergillosis. Med Mycol. 2011;49:S170–6.

    Article  CAS  PubMed  Google Scholar 

  37. Bacci A, Montagnoli C, Perruccio K, et al. Dendritic cells pulsed with fungal RNA induce protective immunity to Candida albicans in hematopoietic transplantation. J Immunol. 2002;168:2904–13.

    Article  CAS  PubMed  Google Scholar 

  38. Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. 1982;298:859–63.

    Article  CAS  PubMed  Google Scholar 

  39. Davis MJ, Eastman AJ, Qiu Y, et al. Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence. J Immunol. 2015;194:2219–31.

    Article  CAS  PubMed  Google Scholar 

  40. Liles WC. Immunomodulatory approaches to augment phagocyte-mediated host defense for treatment of infectious diseases. Semin Respir Infect. 2001;16:11–7.

    Article  CAS  PubMed  Google Scholar 

  41. Su X, Yu Y, Zhong Y, et al. Interferon-gamma regulates cellular metabolism and mRNA translation to potentiate macrophage activation. Nat Immunol. 2015;16:838–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ostuni R, Piccolo V, Barozzi I, et al. Latent enhancers activated by stimulation in differentiated cells. Cell. 2013;152:157–71.

    Article  CAS  PubMed  Google Scholar 

  43. Stevens DA, Brummer E, Clemons KV. Interferon-γ as an Antifungal. J Infect Dis. 2006;194:S33–7.

    Article  CAS  PubMed  Google Scholar 

  44. www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandAproved/ApprovalApplications/TherapeuticBiologicApplications/ucm080426.htm

  45. Filiz S, Uygun DFK, Köksoy S, Şahin E, Yeğin O. In vitro interferon γ improves the oxidative burst activity of neutrophils in patients with chronic granulomatous disease with a subtype of gp91phox deficiency. Cent Eur J Immunol. 2015;40:54–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Abzug MJ, Walsh TJ. Interferon-gamma and colony-stimulating factors as adjuvant therapy for refractory fungal infections in children. Pediatr Infect Dis J. 2004;23:769–73.

    Article  PubMed  Google Scholar 

  47. Armstrong-James D, Teo IA, Shrisvastava S, et al. Exogenous interferon-gamma immunotherapy for invasive fungal infections in kidney transplant patients. Am J Transplant. 2010;10:1796–803.

    Article  CAS  PubMed  Google Scholar 

  48. Delsing CE, Gresnigt MS, Leentjens J, et al. Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series. BMC Infect Dis. 2014;14:166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Safdar A, Rodriguez G, Ohmagari N, et al. The safety of interferon-gamma-1b therapy for invasive fungal infections after hematopoietic stem cell transplantation. Cancer. 2005;103(4):731–9.

    Article  CAS  PubMed  Google Scholar 

  50. Lewis R, Hogan H, Howell A, Safdar A. Progressive fusariosis: unpredictable posaconazole bioavailability, and feasibility of recombinant interferon-gamma plus granulocyte macrophage-colony stimulating factor for refractory disseminated infection. Leuk Lymphoma. 2008;49(1):163–5.

    Article  CAS  PubMed  Google Scholar 

  51. Weinberger M, Elattar I, Marshall D, et al. Patterns of infection in patients with aplastic anemia and the emergence of Aspergillus as a major cause of death. Medicine. 1992;71:24–43.

    Article  CAS  PubMed  Google Scholar 

  52. Giles FJ. Monocyte-macrophages, granulocyte-macrophage colony-stimulating factor, and prolonged survival among patients with acute myeloid leukemia and stem cell transplants. Clin Infect Dis. 1998;26:1282–9.

    Article  CAS  PubMed  Google Scholar 

  53. Andrew B, Stacy MB, David T, et al. Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation. Blood. 2002;100:4660–7.

    Article  CAS  Google Scholar 

  54. Simone C, Andrea GZ, Stefano F, et al. A phase II study on the safety and efficacy of a single dose of pegfilgrastim for mobilization and transplantation of autologous hematopoietic stem cells in pediatric oncohematology patients. Transfusion. 2011;51:2480–7.

    Article  CAS  Google Scholar 

  55. Gillian MK. Lenograstim. Drugs. 2011;7:679–707.

    Google Scholar 

  56. Lei G, Qin W, Xinghua C, et al. Effects of priming with recombinant human granulocyte colony-stimulating factor on conditioning regimen for high-risk acute myeloid leukemia patients undergoing human leukocyte antigen-haploidentical hematopoietic stem cell transplantation: a multicenter randomized controlled study in Southwest China. Biol Blood Marrow Transplant. 2014;20:1932–9.

    Article  CAS  Google Scholar 

  57. Paolo A, Richard EC. Biologic and molecular effects of granulocyte colony-stimulating factor in healthy individuals: recent findings and current challenges. Blood. 2008;111:1767–72.

    Article  CAS  Google Scholar 

  58. Riccardo R, Giulio C, Ilaria S, et al. Pegfilgrastim: current and future perspectives in the treatment of chemotherapy-induced neutropenia. Future Oncol. 2006;2:667–76.

    Google Scholar 

  59. Bui BN, Chevallier B, Chevreau C, et al. Efficacy of lenograstim on hematologic tolerance to MAID chemotherapy in patients with advanced soft tissue sarcoma and consequences on treatment dose-intensity. J Clin Oncol. 1995;13:2629–36.

    Article  CAS  PubMed  Google Scholar 

  60. Chevreau C, Bui BN, Chevallier B, et al. Phase I-II trial of intensification of the MAID regimen with support of lenograstim (rHuG-CSF) in patients with advanced soft-tissue sarcoma (STS). Am J Clin Oncol. 1999;22:267–72.

    Article  CAS  PubMed  Google Scholar 

  61. Gatzemeier U, Kleisbauer JP, Drings P, et al. Lenograstim as support for ACE chemotherapy of small-cell lung cancer: a phase III, multicenter, randomized study. Am J Clin Oncol. 2000;23:393–400.

    Article  CAS  PubMed  Google Scholar 

  62. Takahashi S. Recombinant human G-CSF combined regimen for allogeneic BMT in myeloid leukemias. Rinshō ketsueki. 1997;38:489–95.

    CAS  PubMed  Google Scholar 

  63. Geissler RG, Schulte P, Ganser A. Treatment with growth factors in myelodysplastic syndromes. Pathol Biol. 1997;45:656–67.

    CAS  PubMed  Google Scholar 

  64. Tabbara IA, Ghazal CD, Ghazal HH. The role of granulocyte colony-stimulating factor in hematopoietic stem cell transplantation. Cancer Investig. 1997;15:353–7.

    Article  CAS  Google Scholar 

  65. Greenberg P, Advani R, Keating A, et al. GM-CSF accelerates neutrophil recovery after autologous hematopoietic stem cell transplantation. Bone Marrow Transplant. 1996;18:1057–64.

    CAS  PubMed  Google Scholar 

  66. Day SJO, Rabinowe SN, Neuberg D, et al. A phase II study of continuous infusion recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission. Blood. 1994;83:2707–14.

    Google Scholar 

  67. Battiwalla M, McCarthy PL. Filgrastim support in allogeneic HSCT for myeloid malignancies: a review of the role of G-CSF and the implications for current practice. Bone Marrow Transplant. 2009;43:351–6.

    Article  CAS  PubMed  Google Scholar 

  68. Kobbe G, Bruns I, Fenk R, Czibere A, Haas R. Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT. Bone Marrow Transplant. 2009;43:669–77.

    Article  CAS  PubMed  Google Scholar 

  69. Piccirillo N, Matteis SD, Vita SD, et al. Kinetics of peg-filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 2007;40:579–83.

    Article  CAS  PubMed  Google Scholar 

  70. Takehiko M, Yoshinobu A, Reiko W, et al. Long-term follow-up of allogeneic hematopoietic stem cell transplantation for de novo acute myelogenous leukemia with a conditioning regimen of total body irradiation and granulocyte colony-stimulating factor-combined high-dose cytarabine. Biol Blood Marrow Transplant. 2008;14:651–7.

    Article  CAS  Google Scholar 

  71. Clifford L, Craig W, Aaron PR, Alister CW. Granulocyte colony-stimulating factor receptor: stimulating granulopoiesis and much more. Int J Biochem Cell Biol. 2009;41:2372–5.

    Article  CAS  Google Scholar 

  72. Ian MW, Olga M, Leah B, et al. Sequential administration of sargramostim and filgrastim in pediatric allogeneic stem cell transplantation recipients undergoing myeloablative conditioning. Pediatr Transplant. 2009;13:464–74.

    Article  CAS  Google Scholar 

  73. Takahashi S, Oshima Y, Okamoto S, et al. Recombinant human granulocyte colony-stimulating factor (G-CSF) combined conditioning regimen for allogeneic bone marrow transplantation (BMT) in standard-risk myeloid leukemia. Am J Hematol. 1998;57:303–8.

    Article  CAS  PubMed  Google Scholar 

  74. Teshima H, Ishikawa J, Kitayama H, et al. Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. Exp Hematol. 1989;17:853–8.

    CAS  PubMed  Google Scholar 

  75. Asano S, Masaoka T, Takaku F. Clinical effect of recombinant human granulocyte colony-stimulating factor in bone marrow transplantation. The Japan rhG-CSF Clinical Study Group. Gan To Kagaku Ryoho. 1990;17:1201–9.

    CAS  PubMed  Google Scholar 

  76. Sandro D, Roberto R, Chiara M, et al. Clinical benefits of granulocyte colony-stimulating factor therapy after hematopoietic stem cell transplant in children: results of a prospective randomized trial. Haematologica. 2002;87:1274–80.

    Google Scholar 

  77. César Gómez R, Alvaro Pinto M, Manuel González B. Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia. Clin Transl Oncol. 2006;8:729–34.

    Article  Google Scholar 

  78. Christian S, Michael S, Hans S, et al. Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy. Blood. 2011;117:2121–8.

    Article  CAS  Google Scholar 

  79. Roilides E, Walsh TJ, Pizzo PA, Rubin M. Granulocyte colony-stimulating factor enhances the phagocytic and bactericidal activity of normal and defective human neutrophils. J Infect Dis. 1991;163:579–83.

    Article  CAS  PubMed  Google Scholar 

  80. Lechner AJ, Lamprech KE, Potthoff LH, Tredway TL, Matuschak GM. Recombinant GM-CSF reduces lung injury and mortality during neutropenic Candida sepsis. Am J Phys. 1994;266:8.

    Google Scholar 

  81. Mayer P, Schütze E, Lam C, Kricek F, Liehl E. Recombinant murine granulocyte-macrophage colony-stimulating factor augments neutrophil recovery and enhances resistance to infections in myelosuppressed mice. J Infect Dis. 1991;16:584–90.

    Article  Google Scholar 

  82. Smith PD, Lamerson CL, Banks SM, et al. Granulocyte-macrophage colony-stimulating factor augments human monocyte fungicidal activity for Candida albicans. J Infect Dis. 1990;161:999–1005.

    Article  CAS  PubMed  Google Scholar 

  83. Djeu JY, Blanchard DK, Halkias D, Friedman H. Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol. 1986;137:2980–4.

    CAS  PubMed  Google Scholar 

  84. Weisbart RH, Golde DW, Clark SC, Wong GG, Gasson JC. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator. Nature. 1985;314:361–3.

    Article  CAS  PubMed  Google Scholar 

  85. Peters BG, Adkins DR, Harrison BR, et al. Antifungal effects of yeast-derived rhu-GM-CSF in patients receiving high-dose chemotherapy given with or without autologous stem cell transplantation: a retrospective analysis. Bone Marrow Transplant. 1996;18:93–102.

    CAS  PubMed  Google Scholar 

  86. Safdar A, Rodriguez G, Zuniga J, Al Akhrass F, Georgescu G, Pande A. Granulocyte macrophage colony-stimulating factor in 66 patients with myeloid or lymphoid neoplasms and recipients of hematopoietic stem cell transplantation with invasive fungal disease. Acta Haematol. 2013;129(1):26–34.

    Article  CAS  PubMed  Google Scholar 

  87. Graw RG Jr, Herzig G, Perry S, Henderson ES. Normal granulocyte transfusion therapy: treatment of septicemia due to gram-negative bacteria. N Engl J Med. 1972;287:367–71.

    Article  PubMed  Google Scholar 

  88. Raubitschek AA, Levin AS, Stites DP, Shaw EB, Fudenberg HH. Normal granulocyte infusion therapy for aspergillosis in chronic granulomatous disease. Pediatrics. 1973;51:230–3.

    CAS  PubMed  Google Scholar 

  89. Debelak KM, Epstein RB, Andersen BR. Granulocyte transfusions in leukopenic dogs: in vivo and in vitro function of granulocytes obtained by continuous-flow filtration leukapheresis. Blood. 1974;43:757–66.

    CAS  PubMed  Google Scholar 

  90. Dale DC, Reynolds HY, Pennington JE, et al. Experimental pneumonia die to Pseudomonas in dogs: controlled trial of granulocyte transfusion therapy. J Infect Dis. 1974;130:S143–4.

    Article  PubMed  Google Scholar 

  91. Lowenthal RM, Grossman L, Goldman JM, et al. Granulocyte transfusions in treatment of infections in patients with acute leukaemia and aplastic anaemia. Lancet. 1975;1:353–8.

    Article  CAS  PubMed  Google Scholar 

  92. Gercovich FG, Richman SP, Rodriguez V, et al. Successful control of systemic Aspergillus niger infections in two patients with acute leukemia. Cancer. 1975;36:2271–6.

    Article  CAS  PubMed  Google Scholar 

  93. Petersen FB, Buckner CD, Clift RA, et al. Prevention of nosocomial infection sin marrow transplant patients: a prospective randomized comparison of systemic antibiotics versus granulocyte transfusions. Infect Control. 1986;7:586–92.

    Article  CAS  PubMed  Google Scholar 

  94. Goering P, Berlinger NT, Weisdorf DJ. Aggressive combined modality treatment of progressive sinonasal fungal infections in immunocompromised patients. Am J Med. 1988;85:619–23.

    Article  CAS  PubMed  Google Scholar 

  95. Gerson SL, Talbot GH, Hurwitz S, et al. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med. 1984;100:345–51.

    Article  CAS  PubMed  Google Scholar 

  96. Clarke K, Szer J, Shelton M, Coghlan D, Grigg A. Multiple granulocyte transfusions facilitating successful unrelated bone marrow transplantation in a patient with very severe aplastic anemia complicated by suspected fungal infection. Bone Marrow Transplant. 1995;16:723–6.

    CAS  PubMed  Google Scholar 

  97. Catalano L, Fontana R, Scarpato N, et al. Combined treatment with amphotericin-B and granulocyte transfusion with G-CSF-stimulated donors in an aplastic patient with invasive aspergillosis undergoing bone marrow transplantation. Haematologica. 1997;82:71–2.

    CAS  PubMed  Google Scholar 

  98. Bhatia S, McCullough J, Perry EH, et al. Granulocyte transfusions: efficacy in treating fungal infections in neutropenic patients following bone marrow transplantation. Transfusion. 1994;34:226–32.

    Article  CAS  PubMed  Google Scholar 

  99. Vamvakas EC, Pineda AA. Determinants of the efficacy of prophylactic granulocyte transfusions: a meta-analysis. J Clin Apher. 1997;12:74–81.

    Article  CAS  PubMed  Google Scholar 

  100. Martinez M, Chen V, Tong A-J, et al. Experimental evidence that granulocyte transfusions are efficacious in treatment of neutropenic hosts with pulmonary aspergillosis. Antimicrob Agents Chemother. 2013;57:1882–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Safdar A, Hanna HA, Boktour M, et al. Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections. Cancer. 2004;101(12):2859–65.

    Article  PubMed  Google Scholar 

  102. Hubel K, Dale DC, Liles WC. Granulocyte transfusion therapy: update on potential clinical applications. Curr Opin Hematol. 2001;8:161–4.

    Article  CAS  PubMed  Google Scholar 

  103. Yeghen T, Devereux S. Granulocyte transfusion: a review. Vox Sang. 2001;81:87–92.

    Article  CAS  PubMed  Google Scholar 

  104. Hubel K, Carter RA, Liles WC, et al. Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors. Transfusion. 2002;42:1414–21.

    Article  PubMed  Google Scholar 

  105. Lee JJ, Chung IJ, Park MR, et al. Clinical efficacy of granulocyte transfusion therapy in patients with neutropenia-related infections. Leukemia. 2001;25:203–7.

    Article  Google Scholar 

  106. Samadi DS, Goldberg AN, Orlandi RR. Granulocyte transfusion in the management of fulminant invasive fungal rhinosinusitis. Am J Rhinol. 2001;15:263–5.

    Article  CAS  PubMed  Google Scholar 

  107. Illerhaus G, Wirth K, Dwenger A, et al. Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions. Ann Hematol. 2002;81:273–81.

    Article  CAS  PubMed  Google Scholar 

  108. Piccaluga PP, Ricci P, Martinelli G, et al. Prompt resolution of nasal aspergillosis with intranasal instillation of liposomal amphotericin-B (amBisome) and granulocyte transfusions. Leuk Lymphoma. 2004;45:637–8.

    Article  PubMed  Google Scholar 

  109. Grigull L, Beilken A, Schmid H, et al. Secondary prophylaxis of invasive fungal infections with combination antifungal therapy and G-CSF-mobilized granulocyte transfusions in three children with hematological malignancies. Support Care Cancer. 2006;14:783–6.

    Article  PubMed  Google Scholar 

  110. Sachs UJ, Reiter A, Walter T, Bein G, Woessmann W. Safety and efficacy of therapeutic early onset granulocyte transfusions in pediatric patients with neutropenia and severe infections. Transfusion. 2006;46:1909–14.

    Article  PubMed  Google Scholar 

  111. van de Wetering MD, Weggelaar N, Offringa M, Caron HN, Kuijpers TW. Granulocyte transfusions in neutropaenic children: a systematic review of the literature. Eur J Cancer. 2007;43:2082–92.

    Article  PubMed  Google Scholar 

  112. Seidel MG, Minkov M, Witt V, et al. Granulocyte transfusions in children and young adults: does the dose matter? J Pediatr Hematol Oncol. 2009;31:166–72.

    Article  PubMed  Google Scholar 

  113. Kerr JP, Liakopolou E, Brown J, et al. The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogeneic stem cell transplantation. Br J Haematol. 2003;123:114–8.

    Article  PubMed  Google Scholar 

  114. Marfin AA, Price TH. Granulocyte transfusion therapy. J Intensive Care Med. 2015;30:79–88.

    Article  PubMed  Google Scholar 

  115. Massey E, Paulus U, Doree C, Stanworth S. Granulocyte transfusion for preventing infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev. 2009;1:CD005341.

    Google Scholar 

  116. Liles WC, Rodger E, Dale DC. Combined administration of G-CSF and dexamethasone for the mobilization of granulocytes in normal donors: optimization of dosing. Transfusion. 2000;40:642–4.

    Article  CAS  PubMed  Google Scholar 

  117. Liles WC, Huang JE, Llewellyn C, et al. A comparative trial of granulocyte-colony stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers. Transfusion. 1997;37:182–7.

    Article  CAS  PubMed  Google Scholar 

  118. Ikemoto J, Yoshihara S, Fujioka T, et al. Impact of the mobilization regimen and the harvesting technique on the granulocyte yield in health donors for granulocyte transfusion therapy. Transfusion. 2012;52:2646–52.

    Article  PubMed  Google Scholar 

  119. Bendinger WI. Allogeneic transplantation: peripheral blood vs. bone marrow. Curr Opin Oncol. 2012;24:191–6.

    Article  Google Scholar 

  120. Liles WC, Broxmeyer H, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD 3100, a CXCR4 antagonist. Blood. 2003;102:2728–30.

    Article  CAS  PubMed  Google Scholar 

  121. McDermott DH, Liu Q, Ulrick J, et al. The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. Blood. 2011;118:4957–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Dale DC, Bolyard AA, Kelley ML, et al. The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. Blood. 2011;119:4963–6.

    Article  CAS  Google Scholar 

  123. Safdar A, Rodriguez G, Zuniga J, Al Akhrass F, Pande A. Use of healthy-donor granulocyte transfusions to treat infections in neutropenic patients with myeloid or lymphoid neoplasms: experience in 74 patients treated with 373 granulocyte transfusions. Acta Haematol. 2014;131(1):50–8.

    Article  PubMed  Google Scholar 

  124. Safdar A, Rodriguez GH, Lichtiger B, et al. Recombinant interferon gamma1b immune enhancement in 20 patients with hematologic malignancies and systemic opportunistic infections treated with donor granulocyte transfusions. Cancer. 2006;106(12):2664–71.

    Article  CAS  PubMed  Google Scholar 

  125. Hino M, Suzuki K, Yamane T, et al. Ex vivo expansion of mature human neutrophils with normal functions from purified peripheral blood CD34+ haematopoietic progenitor cells. Br J Haematol. 2000;109:314–21.

    Article  CAS  PubMed  Google Scholar 

  126. McNiece I, Briddell R. Ex vivo expansion of hematopoietic progenitor cells and mature cells. Exp Hematol. 2001;29:3–11.

    Article  CAS  PubMed  Google Scholar 

  127. Marturana F, Timmins NE, Nielsen LK. Short-term exposure of umbilical cord blood CD34+ cells to granulocyte-macrophage colony stimulating factor early in culture improves ex vivo expansion of neutrophils. Cytotherapy. 2011;13:366–77.

    Article  CAS  PubMed  Google Scholar 

  128. Dick EP, Prince LR, Sabroe I. Ex vivo-expanded bone marrow CD34+ derived neutrophils have limited bactericidal ability. Stem Cells. 2008;26:2552–63.

    Article  CAS  PubMed  Google Scholar 

  129. Brunck MEG, Nielsen LK. Concise review: next-generation cell therapies to prevent infection in neutropenic patients. Stem Cells Transl Med. 2014;3:541–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Safdar A. Immunotherapy for invasive mold disease in severely immunosuppressed patients. Clin Infect Dis. 2013;57(1):94–100.

    Article  PubMed  CAS  Google Scholar 

  131. Safdar A. Immunomodulation therapy for invasive aspergillosis: discussion on myeloid growth factors, recombinant cytokines, and antifungal drug immune modulation. Curr Fungal Infect Rep. 2010;4(1):1–7.

    Article  PubMed  Google Scholar 

  132. Safdar A. Antifungal immunity and adjuvant cytokine immune enhancement in cancer patients with invasive fungal infections. Clin Microbiol Infect. 2007;13(1):1–4.

    Article  CAS  PubMed  Google Scholar 

  133. Safdar A. Strategies to enhance immune function in hematopoietic transplantation recipients who have fungal infections. Bone Marrow Transplant. 2006;38(5):327–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William K. Decker .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Decker, W.K., Halpert, M.M., Konduri, V., Liang, D., Hampton, C.N., Safdar, A. (2019). Immunotherapy for Invasive Mold Disease in Transplant Patients: Dendritic Cell Immunotherapy, Interferon Gamma, Recombinant Myeloid Growth Factors, and Healthy Donor Granulocyte Transfusions. In: Safdar, A. (eds) Principles and Practice of Transplant Infectious Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-9034-4_58

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9034-4_58

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-9032-0

  • Online ISBN: 978-1-4939-9034-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics