Chapter 39 : Invasive Aspergillosis in Malignancy and Stem Cell Transplant Recipients

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Invasive mycoses represent a major cause of morbidity and mortality in patients with malignancy or undergoing hematopoietic stem cell transplantation (HSCT). Recently it has been shown that the Toll-like receptor system could play an important role in the development of invasive aspergillosis in patients receiving chemotherapy or after HSCT, and there is evidence suggesting that the involvement of Toll-like receptors during infection is influenced by the immunological status of the host. The upper and lower respiratory tracts represent the most frequent locations of infection in all patient categories and age groups. Among echinocandins, caspofungin has been approved for salvage therapy in patients with invasive aspergillosis, since it has been demonstrated to be well-tolerated and with a 39% response in patients with refractory infections. However, in this study as in other salvage therapy trials, the need for salvage therapy was established in the presence of progression of disease or failure to improve clinically despite receiving at least 7 days of “standard therapy” (mainly amphotericin B deoxycholate, liposomal amphotericin B, or itraconazole). The degree of immunosuppression and the status of the underlying disease could represent very important factors acting upon a patient’s survival. For example, in the voriconazole study, success was observed in 63% of neutropenic patients receiving chemotherapy but in only 32% of recipients of allogeneic HSCT.

Citation: Castagnola E, Viscoli C. 2009. Invasive Aspergillosis in Malignancy and Stem Cell Transplant Recipients, p 519-530. In Latgé J, Steinbach W (ed), and Aspergillosis. ASM Press, Washington, DC. doi: 10.1128/9781555815523.ch39
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1. Abbasi, S.,, J. L. Shenep,, W. T. Hughes, and, P. M. Flynn. 1999. aspergillosis in children with cancer: a 34-year experience. Clin. Infect. Dis. 29: 12101219.
2. Alangaden, G. J.,, M. Wahiduzzaman, and, P. H. Chandrasekar. 2002. Aspergillosis: the most common community-acquired pneumonia with gram-negative bacilli as copathogens in stem cell transplant recipients with graft-versus-host disease. Clin. Infect. Dis. 35: 659664.
3. Aliff, T. B.,, P. G. Maslak,, J. G. Jurcic,, M. L. Heaney,, K. N. Cathcart,, K. A. Sepkowitz, and, M. A. Weiss. 2003. Refractory Aspergillus pneumonia in patients with acute leukemia: successful therapy with combination caspofungin and liposomal amphotericin. Cancer 97: 10251032.
4. Anaissie, E., and, M. Nucci. 2003. Risk and epidemiology of infections after autologous hemopoietic stem cell transplantation, p. 3950. In R. A. Bowden,, P. Ljungman, and, C. V. Paya (ed.), Transplant Infections. Lippincott Williams & Wilkins, Philadelphia, PA.
5. Anaissie, E. J.,, S. R. Penzak, and, M. C. Dignani. 2002. The hospital water supply as a source of nosocomial infections: a plea for action. Arch. Intern. Med. 162: 14831492.
6. Ascioglu, S.,, J. H. Rex,, B. de Pauw,, J. E. Bennett,, J. Bille,, F. Crokaert,, D. W. Denning,, J. P. Donnelly,, J. E. Edwards,, Z. Erjavec,, D. Fiere,, O. Lortholary,, J. Maertens,, J. F. Meis,, T. F. Patterson,, J. Ritter,, D. Selleslag,, P. M. Shah,, D. A. Stevens, and, T. J. Walsh. 2002. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin. Infect. Dis. 34: 714.
7. Baddley, J. W.,, T. P. Stroud,, D. Salzman, and, P. G. Pappas. 2001. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin. Infect. Dis. 32: 13191324.
8. Balloy, V.,, M. Huerre,, J. P. Latgé, and, M. Chignard. 2005. Differences in patterns of infection and inflammation for corticosteroid treatment and chemotherapy in experimental invasive pulmonary aspergillosis. Infect. Immun. 73: 494503.
9. Barker, J. N.,, R. E. Hough,, J. A. van Burik,, T. E. DeFor,, M. L. MacMillan,, M. R. O’Brien, and, J. E. Wagner. 2005. Serious infections after unrelated donor transplantation in 136 children: impact of stem cell source. Biol. Blood Marrow Transplant. 11: 362370.
10. Benet, T.,, M. C. Nicolle,, A. Thiebaut,, M. A. Piens,, F. E. Nicolini,, X. Thomas,, S. Picot,, M. Michallet, and, P. Vanhems. 2007. Reduction of invasive aspergillosis incidence among immunocompromised patients after control of environmental exposure. Clin. Infect. Dis. 45: 682686.
11. Benjamin, D. K. J.,, W. C. Miller,, S. Bayliff,, L. Martel,, K. A. Alexander, and, P. L. Martin. 2002. Infections diagnosed in the first year after pediatric stem cell transplantation. Pediatr. Infect. Dis. J. 21: 227234.
12. Bernard, A.,, D. Caillot,, J. F. Couaillier,, O. Casasnovas,, H. Guy, and, J. P. Favre. 1997. Surgical management of invasive pulmonary aspergillosis in neutropenic patients. Ann. Thorac. Surg. 64: 14411447.
13. Bjorklund, A.,, J. Aschan,, M. Labopin,, M. Remberger,, O. Ringden,, J. Winiarski, and, P. Ljungman. 2007. Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation. Bone Marrow Transplant. 40: 10551062.
14. Boeckh, M., and, K. A. Marr. 2002. Infection in hematopoietic stem cell transplantation, p. 527571. In R. H. Rubin and L. S. Young (ed.), Clinical Approach to Infection in the Compromised Host. Klu-wer Academic/Plenum, New York, NY.
15. Brodoefel, H.,, M. Vogel,, H. Hebart,, H. Einsele,, R. Vonthein,, C. Claussen, and, M. Horger. 2006. Long-term CT follow-up in 40 non-HIV immunocompromised patients with invasive pulmonary aspergillosis: kinetics of CT morphology and correlation with clinical findings and outcome. Am. J. Roentgenol. 187: 404413.
16. Brummer, E.,, M. Kamberi, and, D. A. Stevens. 2003. Regulation by granulocyte-macrophage colony-stimulating factor and/or steroids given in vivo of proinflammatory cytokine and chemokine production by bronchoalveolar macrophages in response to Aspergillus co-nidia. J. Infect. Dis. 187: 705709.
17. Caillot, D.,, O. Casasnovas,, A. Bernard,, J. F. Couaillier,, C. Durand,, B. Cuisenier,, E. Solary,, F. Piard,, T. Petrella,, A. Bonnin,, G. Couil-lault,, M. Dumas, and, H. Guy. 1997. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J. Clin. Oncol. 15: 139147.
18. Caillot, D.,, J. F. Couaillier,, A. Bernard,, O. Casasnovas,, D. W. Denning,, L. Mannone,, J. Lopez,, G. Couillault,, F. Piard,, O. Vagner, and, H. Guy. 2001. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. J. Clin. Oncol. 19: 253259.
19. Castagnola, E.,, F. Bagnasco,, M. Faraci,, I. Caviglia,, S. Caruso,, B. Cappelli,, C. Moroni,, G. Morreale,, A. Timitilli,, G. Tripodi,, E. La-nino, and, R. Haupt. 2008. Incidence of bacteremias and invasive mycoses in children undergoing allogeneic hematopietic stem cell transplantation: a single center experience. Bone Marrow Transplant. 41: 339347.
20. Castagnola, E.,, I. Caviglia,, A. Pistorio,, F. Fioredda,, C. Micalizzi,, C. Viscoli, and, R. Haupt. 2005. Bloodstream infections and invasive mycoses in children undergoing acute leukaemia treatment: a 13-year experience at a single Italian institution. Eur. J. Cancer 41: 14391445.
21. Castagnola, E.,, S. Cesaro,, M. Giacchino,, S. Livadiotti,, F. Tucci,, G. Zanazzo,, D. Caselli,, I. Caviglia,, S. Parodi,, R. Rondelli,, P. E. Cor-nelli,, R. Mura,, N. Santoro,, G. Russo,, R. De Santis,, S. Buffardi,, C. Viscoli,, R. Haupt, and, M. R. Rossi. 2006. Fungal infections in children with cancer: a prospective, multicenter surveillance study. Pe-diatr. Infect. Dis. J. 25: 634639.
22. Castagnola, E.,, V. Fontana,, I. Caviglia,, S. Caruso,, M. Faraci,, F. Fio-redda,, M. L. Garre,, C. Moroni,, M. Conte,, G. Losurdo,, F. Scuderi,, R. Bandettini,, P. Toma,, C. Viscoli, and, R. Haupt. 2007. A prospective study on the epidemiology of febrile episodes during chemotherapy-induced neutropenia in children with cancer or after hemopoietic stem cell transplantation. Clin. Infect. Dis. 45: 12961304.
23. Cesaro, S.,, G. Cecchetto,, F. De Corti,, P. Dodero,, M. Giacchino,, I. Caviglia,, F. Fagioli,, S. Livadiotti,, F. Salin,, D. Caselli, and, E. Cas-tagnola. 2007a. Results of a multicenter retrospective study of a combined medical and surgical approach to pulmonary aspergillosis in pediatric neutropenic patients. Pediatr. Blood Cancer 49: 909913.
24. Cesaro, S.,, M. Giacchino,, F. Locatelli,, M. Spiller,, B. Buldini,, C. Cas-tellini,, D. Caselli,, E. Giraldi,, F. Tucci,, G. Tridello,, M. R. Rossi, and, E. Castagnola. 2007b. Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients. BMC Infect. Dis. 7: 28.
25. Cesaro, S.,, T. Toffolutti,, C. Messina,, E. Calore,, R. Alaggio,, R. Cu-sinato,, M. Pillon, and, L. Zanesco. 2004. Safety and efficacy of cas-pofungin and liposomal amphotericin B, followed by voriconazole in young patients affected by refractory invasive mycosis. Eur. J. Haematol. 73: 5055.
26. Chamilos, G.,, M. Luna,, R. Lewis,, G. Bodey,, R. Chemaly,, J. Tarrand,, A. Safdar,, I. Raad, and, D. Kontoyiannis. 2006. 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 91: 986989.
27. Chandrasekar, P. H., and, J. I. Ito. 2005. Amphotericin B lipid complex in the management of invasive aspergillosis in immunocompromised patients. Clin. Infect. Dis. 40: (Suppl. 6): S392S400.
28. Chapman, S. W. 2007a. Azole prophylaxis to prevent invasive fungal infections in patients with profound neutropenia. Curr. Infect. Dis. Rep. 9: 446447.
29. Chapman, S. W. 2007b. Azole prophylaxis to prevent invasive fungal infections in patients with severe graft-versus-host disease. Curr. Infect. Dis. Rep. 9: 445446.
30. Chignard, M.,, V. Balloy,, J. Sallenave, and, M. Si-Tahar. 2007. Role of Toll-like receptors in lung innate defense against invasive aspergillosis. Distinct impact in immunocompetent and immunocompromised hosts. Clin. Immunol. 124: 238243.
31. Cordonnier, C.,, P. Ribaud,, R. Herbrecht,, N. Milpied,, D. Valteau-Couanet,, C. Morgan, and, A. Wade. 2006. Prognostic factors for death due to invasive aspergillosis after hematopoietic stem cell transplantation: a 1-year retrospective study of consecutive patients at French transplantation centers. Clin. Infect. Dis. 42: 955963.
32. Cornely, O. A.,, J. Maertens,, M. Bresnik,, R. Ebrahimi,, A. J. Ullmann,, E. Bouza,, C. P. Heussel,, O. Lortholary,, C. Rieger,, A. Boehme,, M. Aoun,, H. A. Horst,, A. Thiebaut,, M. Ruhnke,, D. Reichert,, N. Vi-anelli,, S. W. Krause,, E. Olavarria, and, R. Herbrecht. 2007a. Li-posomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad Trial). Clin. Infect. Dis. 44: 12891297.
33. Cornely, O. A.,, J. Maertens,, D. J. Winston,, J. Perfect,, A. J. Ullmann,, T. J. Walsh,, D. Helfgott,, J. Holowiecki,, D. Stockelberg,, Y. T. Goh,, M. Petrini,, C. Hardalo,, R. Suresh, and, D. Angulo-Gonzalez. 2007b. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 356: 348359.
34. Cornet, M.,, L. Fleury,, C. Maslo,, J. F. Bernard, and, G. Brucker. 2002. Epidemiology of invasive aspergillosis in France: a six-year multi-centric survey in the Greater Paris area. J. Hosp. Infect. 51: 288296.
35. Denning, D. W. 1998. Invasive aspergillosis. Clin. Infect. Dis. 26: 781803.
36. Denning, D. W. 2007. Comparison of 2 studies of treatment of invasive aspergillosis. Clin. Infect. Dis. 45: 11061108.
37. De Pauw, B., and, P. E. Verveij. 2005. Infections in patients with he-matologic malignancies, p. 34323441. In G. L. Mandell,, J. E. Bennett, and, R. Doolin (ed.), Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia, PA.
38. De Pauw, B. E., and, J. P. Donnelly. 2007. Prophylaxis and aspergillosis: has the principle been proven? N. Engl. J. Med. 356: 409411.
39. Donnelly, J. P., and, B. E. De Pauw. 2005. Infections in the immunocompromised host: general principles, p. 34213432. In G. L. Mandell,, J. E. Bennett, and, R. Doolin (ed.), Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia, PA.
40. Dvorak, C. C.,, W. J. Steinbach,, J. M. Brown, and, R. Agarwal. 2005. Risks and outcomes of invasive fungal infections in pediatric patients undergoing allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 36: 621629.
41. Ezzet, F.,, D. Wexler,, R. Courtney,, G. Krishna,, J. Lim, and, M. Laugh-lin. 2005. Oral bioavailability of posaconazole in fasted healthy subjects: comparison between three regimens and basis for clinical dosage recommendations. Clin. Pharmacokinet. 44: 211220.
42. Fukuda, T.,, M. Boeckh,, R. Carter,, B. Sandmaier,, M. Maris,, D. Ma-loney,, P. Martin,, R. Storb, and, K. Marr. 2003. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoi-etic stem cell transplants after nonmyeloablative conditioning. Blood 102: 827833.
43. Fukuda, T.,, M. Boeckh,, K. A. Guthrie,, D. K. Mattson,, S. Owens,, A. Wald,, B. M. Sandmaier,, L. Corey,, R. F. Storb, and, K. A. Marr. 2004. Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center. Biol. Blood Marrow Transplant. 10: 494503.
44. Grazziutti, M. L.,, J. H. Rex,, R. E. Cowart,, E. J. Anaissie,, A. Ford, and, C. A. Savary. 1997. Aspergillus fumigatus conidia induce a Th1-type cytokine response. J. Infect. Dis. 176: 15791583.
45. Greene, R. E.,, H. T. Schlamm,, J. W. Oestmann,, P. Stark,, C. Durand,, O. Lortholary,, J. R. Wingard,, R. Herbrecht,, P. Ribaud,, T. F. Patterson,, P. F. Troke,, D. W. Denning,, J. E. Bennett,, B. E. de Pauw, and, R. H. Rubin. 2007. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin. Infect. Dis. 44: 373379.
46. Groll, A. H.,, M. Kurz,, W. Schneider,, V. Witt,, H. Schmidt,, M. Schneider, and, D. Schwabe. 1999. Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival. Mycoses 42: 431442.
47. Grow, W. B.,, J. S. Moreb,, D. Roque,, K. Manion,, H. Leather,, V. Reddy,, S. A. Khan,, K. J. Finiewicz,, H. Nguyen,, C. J. Clancy,, P. S. Mehta, and, J. R. Wingard. 2002. Late onset of invasive Aspergillus infection in bone marrow transplant patients at a university hospital. Bone Marrow Transplant. 29: 1519.
48. Gubbins, P. O.,, G. Krishna,, A. Sansone-Parsons,, S. R. Penzak,, L. Dong,, M. Martinho, and, E. J. Anaissie. 2006. Pharmacokinetics and safety of oral posaconazole in neutropenic stem cell transplant recipients. Antimicrob. Agents Chemother. 50: 19931999.
49. Habicht, J. M.,, P. Matt,, J. R. Passweg,, F. Reichenberger,, A. Gratwohl,, H. R. Zerkowski, and, M. Tamm. 2001. Invasive pulmonary fungal infection in hematologic patients: is resection effective? Hematol. J. 2: 250256.
50. Hajjeh, R. A., and, D. W. Warnock. 2001. Counterpoint: invasive aspergillosis and the environment—rethinking our approach to prevention. Clin. Infect. Dis. 33: 15491552.
51. Haupt, R.,, M. Romanengo,, T. Fears,, C. Viscoli, and, E. Castagnola. 2001. Incidence of septicaemias and invasive mycoses in children undergoing treatment for solid tumours: a 12-year experience at a single Italian institution. Eur. J. Cancer 37: 24132419.
52. Hebart, H.,, C. Bollinger,, P. Fisch,, J. Sarfati,, C. Meisner,, M. Baur,, J. Loeffler,, M. Monod,, J. P. Latgé, and, H. Einsele. 2002. Analysis of T-cell responses to Aspergillus fumigatus antigens in healthy individuals and patients with hematologic malignancies. Blood 100: 45214528.
53. Herbrecht, R.,, D. W. Denning,, T. F. Patterson,, J. E. Bennett,, R. E. Greene,, J. W. Oestmann,, W. V. Kern,, K. A. Marr,, P. Ribaud,, O. Lortholary,, R. Sylvester,, R. H. Rubin,, J. R. Wingard,, P. Stark,, C. Durand,, D. Caillot,, E. Thiel,, P. H. Chandrasekar,, M. R. Hodges,, H. T. Schlamm,, P. F. Troke, and, B. de Pauw. 2002. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N. Engl. J. Med. 347: 408415.
54. Hori, A.,, M. Kami,, Y. Kishi,, U. Machida,, T. Matsumura, and, T. Kashima. 2002. Clinical significance of extra-pulmonary involvement of invasive aspergillosis: a retrospective autopsy-based study of 107 patients. J. Hosp. Infect. 50: 175182.
55. Hovi, L.,, U. M. Saarinen-Pihkala,, K. Vettenranta, and, H. Saxen. 2000. Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years. Bone Marrow Transplant. 26: 9991004.
56. Hovi, L.,, H. Saxen,, U. M. Saarinen-Pihkala,, K. Vettenranta,, T. Meri, and, M. Richardson. 2007. Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders. Pediatr. Blood Cancer 48: 2834.
57. Hoyle, C., and, J. M. Goldman. 1994. Life-threatening infections occurring more than 3 months after BMT. 18 UK Bone Marrow Transplant Teams. Bone Marrow Transplant. 14: 247252.
58. Humphreys, H. 2004. Positive-pressure isolation and the prevention of invasive aspergillosis. What is the evidence? J. Hosp. Infect. 56: 93100.
59. Jantunen, E.,, A. Piilonen,, L. Volin,, T. Parkkali,, P. Koukila-Kahkola,, T. Ruutu, and, P. Ruutu. 2000. Diagnostic aspects of invasive As-pergillus infections in allogeneic BMT recipients. Bone Marrow Transplant. 25: 867871.
60. Junghanss, C., and, K. A. Marr. 2002. Infectious risks and outcomes after stem cell transplantation: are nonmyeloablative transplants changing the picture? Curr. Opin. Infect. Dis. 15: 347353.
61. Kesh, S.,, N. Y. Mensah,, P. Peterlongo,, D. Jaffe,, K. Hsu,, V. D. B. M,, R. O’Reilly,, E. Pamer,, J. Satagopan, and, G. A. Papanicolaou. 2005. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann. N. Y. Acad. Sci. 1062: 95103.
62. Kojima, R.,, M. Kami,, Y. Nannya,, E. Kusumi,, M. Sakai,, Y. Tanaka,, Y. Kanda,, S. Mori,, S. Chiba,, S. Miyakoshi,, K. Tajima,, H. Hirai,, S. Taniguchi,, H. Sakamaki, and, Y. Takaue. 2004. Incidence of invasive aspergillosis after allogeneic hematopoietic stem cell transplantation with a reduced-intensity regimen compared with transplantation with a conventional regimen. Biol. Blood Marrow Transplant. 10: 645652.
63. Kojima, R.,, U. Tateishi,, M. Kami,, N. Murashige,, Y. Nannya,, E. Ku-sumi,, M. Sakai,, Y. Tanaka,, Y. Kanda,, S. Mori,, S. Chiba,, M. Ku-sumoto,, S. Miyakoshi,, H. Hirai,, S. Taniguchi,, H. Sakamaki, and, Y. Takaue. 2005. Chest computed tomography of late invasive aspergillosis after allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 11: 506511.
64. Kontoyiannis, D. P.,, R. Hachem,, R. E. Lewis,, G. A. Rivero,, H. A. Torres,, J. Thornby,, R. Champlin,, H. Kantarjian,, G. P. Bodey, and, I. I. Raad. 2003. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer 98: 292299.
65. Lanciotti, M.,, S. Pigullo,, T. Lanza,, C. Dufour,, I. Caviglia, and, E. Castagnola. 2008. Possible role of toll-like receptor 9 polymorphism in chemotherapy-related invasive mold infections in children with hematological malignancies. Pediatr. Blood Cancer 50: 944.
66. Levine, D.,, O. Navarro,, G. Chaudry,, J. Doyle, and, S. Blaser. 2007. Imaging the complications of bone marrow transplantation in children. Radiographics 27: 307324.
67. Lin, S. J.,, J. Schranz, and, S. M. Teutsch. 2001. Aspergillosis case-fatality rate: systematic review of the literature. Clin. Infect. Dis. 32: 358366.
68. Maertens, J.,, A. Glasmacher,, R. Herbrecht,, A. Thiebaut,, C. Cordon-nier,, B. H. Segal,, J. Killar,, A. Taylor,, N. Kartsonis,, T. F. Patterson,, M. Aoun,, D. Caillot, and, C. Sable. 2006. Multicenter, noncompar-ative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. Cancer 107: 28882897.
69. Maertens, J.,, I. Raad,, G. Petrikkos,, M. Boogaerts,, D. Selleslag,, F. Petersen,, C. Sable,, N. Kartsonis,, A. Ngai,, A. Taylor,, T. Patterson,, D. Denning, and, T. Walsh. 2004. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin. Infect. Dis. 39: 15631571.
70. Manuel, R. J., and, C. C. Kibbler. 1998. The epidemiology and prevention of invasive aspergillosis. J. Hosp. Infect. 39: 95109.
71. Marchetti, O., and, T. Calandra. 2004. Infections in the neutropenic cancer patient, p. 10771092. In J. Cohen and, E. G. Powderly (ed.), Infectious Diseases. Mosby, London, United Kingdom.
72. Marr, K. A.,, M. Boeckh,, R. A. Carter,, H. W. Kim, and, L. Corey. 2004. Combination antifungal therapy for invasive aspergillosis. Clin. Infect. Dis. 39: 797802.
73. Marr, K. A.,, M. Boeckh, and, H. Kim. 2005. Combination antifungal therapy for invasive aspergillosis. Clin. Infect. Dis. 40: 10751076. (Author’s reply.)
74. Marr, K. A., and, R. A. Bowden. 1999. Fungal infections in patients undergoing blood and marrow transplantation. Transplant. Infect. Dis. 1: 237246.
75. Marr, K. A.,, R. A. Carter,, M. Boeckh,, P. Martin, and, L. Corey. 2002. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100: 43584366.
76. Martin, S. I.,, F. M. Marty,, K. Fiumara,, S. P. Treon,, J. G. Gribben, and, L. R. Baden. 2006. Infectious complications associated with alemtuzumab use for lymphoproliferative disorders. Clin. Infect. Dis. 43: 1624.
77. Martino, P.,, C. Girmenia,, M. Venditti,, A. Micozzi,, G. Gentile,, R. Raccah,, E. Martinelli,, E. Rendina, and, F. Mandelli. 1990. Spontaneous pneumothorax complicating pulmonary mycetoma in patients with acute leukemia. Rev. Infect. Dis. 12: 611617.
78. Martino, R.,, R. Parody,, T. Fukuda,, J. Maertens,, K. Theunissen,, A. Ho,, G. Mufti,, N. Kroger,, A. Zander,, D. Heim,, M. Paluszewska,, D. Selleslag,, K. Steinerova,, P. Ljungman,, S. Cesaro,, A. Nihtinen,, C. Cordonnier,, L. Vazquez,, M. López-Duarte,, J. Lopez,, R. Cabrera,, M. Rovira,, S. Neuburger,, O. Cornely,, A. Hunter,, K. Marr,, H. Dornbusch, and, H. Einsele. 2006. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 108: 29282936.
79. Martino, R.,, M. Subira,, M. Rovira,, C. Solano,, L. Vazquez,, G. F. Sanz,, A. Urbano-Ispizua,, S. Brunet, and, R. De la Camara. 2002. Invasive fungal infections after allogeneic peripheral blood stem cell transplantation: incidence and risk factors in 395 patients. Br. J. Hae-matol. 116: 475482.
80. Miceli, M. H.,, J. Maertens,, K. Buve,, M. Grazziutti,, G. Woods,, M. Rahman,, B. Barlogie, and, E. J. Anaissie. 2007. Immune reconsti-tution inflammatory syndrome in cancer patients with pulmonary aspergillosis recovering from neutropenia: proof of principle, description, and clinical and research implications. Cancer 110: 112120.
81. Mihu, C.,, E. King,, O. Yossepovitch,, Y. Taur,, A. Jakubowski,, E. Pa-mer, and, G. Papanicolaou. 2008. Risk factors and attributable mortality of late aspergillosis after T-cell depleted hematopoietic stem cell transplantation. Transplant. Infect. Dis. 10: 162167.
82. Morgan, J.,, K. A. Wannemuehler,, K. A. Marr,, S. Hadley,, D. P. Kon-toyiannis,, T. J. Walsh,, S. K. Fridkin,, P. G. Pappas, and, D. W. Warnock. 2005. Incidence of invasive aspergillosis following he-matopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program. Med. Mycol. 43: (Suppl. 1): S49S58.
83. Ng, T. T.,, G. D. Robson, and, D. W. Denning. 1994. Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis. Microbiology 140: 24752479.
84. Nihtinen, A.,, V. Anttila,, M. Richardson,, T. Meri,, L. Volin, and, T. Ruutu. 2007. The utility of intensified environmental surveillance for pathogenic moulds in a stem cell transplantation ward during construction work to monitor the efficacy of HEPA filtration. Bone Marrow Transplant. 40: 457460.
85. Ochs, L.,, X. O. Shu,, J. Miller,, H. Enright,, J. Wagner,, A. Filipovich,, W. Miller, and, D. Weisdorf. 1995. Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients. Blood 86: 39793986.
86. Offner, F.,, C. Cordonnier,, P. Ljungman,, H. G. Prentice,, D. Engelhard,, D. De Bacquer,, F. Meunier, and, B. De Pauw. 1998. Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin. Infect. Dis. 26: 10981103.
87. Ohmagari, N.,, I. I. Raad,, R. Hachem, and, D. P. Kontoyiannis. 2004. Invasive aspergillosis in patients with solid tumors. Cancer 101: 23002302.
88. Orciuolo, E.,, M. Stanzani,, M. Canestraro,, S. Galimberti,, G. Carulli,, R. Lewis,, M. Petrini, and, K. Komanduri. 2007. Effects of Aspergil-lus fumigatus gliotoxin and methylprednisolone on human neutro- phils: implications for the pathogenesis of invasive aspergillosis. J. Leukoc. Biol. 82: 839848.
89. Pagano, L.,, M. Caira,, A. Candoni,, M. Offidani,, L. Fianchi,, B. Mar-tino,, D. Pastore,, M. Picardi,, A. Bonini,, A. Chierichini,, R. Fanci,, C. Caramatti,, R. Invernizzi,, D. Mattei,, M. E. Mitra,, L. Melillo,, F. Aversa,, M. T. Van Lint,, P. Falcucci,, C. G. Valentini,, C. Girmenia, and, A. Nosari. 2006. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica 91: 10681075.
90. Pagano, L.,, M. Caira,, A. Nosari,, M. T. Van Lint,, A. Candoni,, M. Offidani,, T. Aloisi,, G. Irrera,, A. Bonini,, M. Picardi,, C. Caramatti,, R. Invernizzi,, D. Mattei,, L. Melillo,, C. de Waure,, G. Reddiconto,, L. Fianchi,, C. G. Valentini,, C. Girmenia,, G. Leone,, F. Aversa, et al. 2007. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study. Clin. Infect. Dis. 45: 11611170.
91. Pagano, L.,, P. Ricci,, A. Nosari,, A. Tonso,, M. Buelli,, M. Montillo,, L. Cudillo,, A. Cenacchi,, C. Savignana,, L. Melillo, et al. 1995. Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Br. J. Haematol. 89: 500505.
92. Patterson, T. F.,, H. W. Boucher,, R. Herbrecht,, D. W. Denning,, O. Lortholary,, P. Ribaud,, R. H. Rubin,, J. R. Wingard,, B. DePauw,, H. T. Schlamm,, P. Troke, and, J. E. Bennett. 2005. Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin. Infect. Dis. 41: 14481452.
93. Perruccio, K.,, A. Tosti,, E. Burchielli,, F. Topini,, L. Ruggeri,, A. Carotti,, M. Capanni,, E. Urbani,, A. Mancusi,, F. Aversa,, M. F. Martelli,, L. Romani, and, A. Velardi. 2005. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 106: 43974406.
94. Pfeiffer, C. D.,, J. P. Fine, and, N. Safdar. 2006. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin. Infect. Dis. 42: 14171427.
95. Philippe, B.,, O. Ibrahim-Granet,, M. C. Prevost,, M. A. Gougerot-Pocidalo,, M. Sanchez Perez,, A. Van der Meeren, and, J. P. Latgaé. 2003. Killing of Aspergillus fumigatus by alveolar macrophages is mediated by reactive oxidant intermediates. Infect. Immun. 71: 30343042.
96. Raad, I.,, H. Hanna,, C. Osting,, R. Hachem,, J. Umphrey,, J. Tarrand,, H. Kantarjian, and, G. Bodey. 2002. Masking of neutropenic patients on transport from hospital rooms is associated with a decrease in nosocomial aspergillosis during construction. Infect. Control Hosp. Epidemiol. 23: 4143.
97. Roilides, E.,, T. Sein,, M. Roden,, R. L. Schaufele, and, T. J. Walsh. 2001. Elevated serum concentrations of interleukin-10 in nonneutropenic patients with invasive aspergillosis. J. Infect. Dis. 183: 518520.
98. Romani, L. 2004. Immunity to fungal infections. Nat. Rev. Immunol. 4: 123.
99. Rosen, G. P.,, K. Nielsen,, S. Glenn,, J. Abelson,, J. Deville, and, T. B. Moore. 2005. Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution. J. Pediatr. Hematol. Oncol. 27: 135140.
100. Salerno, C. T.,, D. W. Ouyang,, T. S. Pederson,, D. M. Larson,, J. P. Shake,, E. M. Johnson, and, M. A. Maddaus. 1998. Surgical therapy for pulmonary aspergillosis in immunocompromised patients. Ann. Thorac. Surg. 65: 14151419.
101. Saugier-Veber, P.,, A. Devergie,, A. Sulahian,, P. Ribaud,, F. Traore,, H. Bourdeau-Esperou,, E. Gluckman, and, F. Derouin. 1993. Epidemiology and diagnosis of invasive pulmonary aspergillosis in bone marrow transplant patients: results of a 5 year retrospective study. Bone Marrow Transplant. 12: 121124.
102. Sepkowitz, K. A. 2003. Risk and epidemiology of infections after al-logeneic hemopoietic stem cell transplantation, p. 3138. In R. A. Bowden,, P. Ljungman, and, C. V. Paya (ed.), Transplant Infections. Lippincott Williams & Wilkins, Philadelphia, PA.
103. Silvestri, M.,, S. Oddera,, G. A. Rossi, and, P. Crimi. 1996. Sensitization to airborne allergens in children with respiratory symptoms. Ann. Allergy Asthma Immunol. 76: 239244.
104. Sipsas, N. V., and, D. P. Kontoyiannis. 2006. Clinical issues regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin. Infect. Dis. 42: 15841591.
105. Steinbach, W. J. 2005. Pediatric aspergillosis: disease and treatment differences in children. Pediatr. Infect. Dis. J. 24: 358364.
106. Steinbach, W. J.,, R. M. Addison,, L. McLaughlin,, Q. Gerrald,, P. L. Martin,, T. Driscoll,, C. Bentsen,, J. R. Perfect, and, B. D. Alexander. 2007. Prospective Aspergillus galactomannan antigen testing in pe-diatric hematopoietic stem cell transplant recipients. Pediatr. Infect. Dis. J. 26: 558564.
107. Steinbach, W. J., and, K. A. Marr. 2003. Mold infections after he-mopoietic stem cell transplantation, p. 466482. In R. A. Bowden,, P. Ljungman, and, C. V. Paya (ed.), Transplant Infections. Lippincott Williams & Wilkins, Philadelphia, PA.
108. Subira, M.,, R. Martino,, M. Rovira,, L. Vazquez,, D. Serrano, and, R. De La Camara. 2003. Clinical applicability of the new EORTC/MSG classification for invasive pulmonary aspergillosis in patients with hematological malignancies and autopsy-confirmed invasive aspergillosis. Ann. Hematol. 82: 8082.
109. Temeck, B. K.,, D. J. Venzon,, C. A. Moskaluk, and, H. I. Pass. 1994. Thoracotomy for pulmonary mycoses in non-HIV-immunosuppressed patients. Ann. Thorac. Surg. 58: 333338.
110. Thursky, K.,, G. Byrnes,, A. Grigg,, J. Szer, and, M. Slavin. 2004. Risk factors for post-engraftment invasive aspergillosis in allogeneic stem cell transplantation. Bone Marrow Transplant. 34: 115121.
111. Thursky, K. A.,, L. J. Worth,, J. F. Seymour,, H. Miles Prince, and, M. A. Slavin. 2006. Spectrum of infection, risk and recommendations for prophylaxis and screening among patients with lympho-proliferative disorders treated with alemtuzumab. Br. J. Haematol. 132: 312.
112. Todeschini, G.,, C. Murari,, R. Bonesi,, G. Pizzolo,, G. Verlato,, C. Tec-chio,, V. Meneghini,, M. Franchini,, C. Giuffrida,, G. Perona, and, P. Bellavite. 1999. Invasive aspergillosis in neutropenic patients: rapid neutrophil recovery is a risk factor for severe pulmonary complications. Eur. J. Clin. Investig. 29: 453457.
113. Ullmann, A. J.,, J. H. Lipton,, D. H. Vesole,, P. Chandrasekar,, A. Lang-ston,, S. R. Tarantolo,, H. Greinix,, W. Morais de Azevedo,, V. Reddy,, N. Boparai,, L. Pedicone,, H. Patino, and, S. Durrant. 2007. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N. Engl. J. Med. 356: 335347.
114. Upton, A.,, K. A. Kirby,, P. Carpenter,, M. Boeckh, and, K. A. Marr. 2007. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin. Infect. Dis. 44: 531540.
115. van Burik, J., and, D. Weisdorf. 2005. Infections in recipients of he-matopoietic stem cell transplantation, p. 34863501. In G. L. Man-dell,, J. E. Bennett, and, R. Doolin (ed.), Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia, PA.
116. Viscoli, C.,, R. Herbrecht,, H. Akan,, L. Baila,, C. Doyen,, A. Gallamini,, A. Giagounidis,, O. Marchetti,, R. Martino,, L. Meerts,, M. Paesmans,, M. Shivaprakash,, A. J. Ullman, and, J. Maertens. 2007. Caspofungin (C) as first-line therapy of invasive aspergillosis (IA) in haematological patients (pts): a study of the EORTC Infectious Diseases Group. J. Chemother. 19: (Suppl. 3): 36.
117. Vonberg, R. P., and, P. Gastmeier. 2006. Nosocomial aspergillosis in outbreak settings. J. Hosp. Infect. 63: 246254.
118. Wald, A.,, W. Leisenring,, J. A. van Burik, and, R. A. Bowden. 1997. Epidemiology of Aspergillus infections in a large cohort of patients undergoing bone marrow transplantation. J. Infect. Dis. 175: 14591466.
119. Walsh, T. J.,, I. Raad,, T. F. Patterson,, P. Chandrasekar,, G. R. Don-owitz,, R. Graybill,, R. E. Greene,, R. Hachem,, S. Hadley,, R. Her-brecht,, A. Langston,, A. Louie,, P. Ribaud,, B. H. Segal,, D. A. Stevens,, J. A. van Burik,, C. S. White,, G. Corcoran,, J. Gogate,, G. Krishna,, L. Pedicone,, C. Hardalo, and, J. R. Perfect. 2007. Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial. Clin. Infect. Dis. 44: 212.
120. Warris, A.,, P. Gaustad,, J. F. Meis,, A. Voss,, P. E. Verweij, and, T. G. Abrahamsen. 2001. Recovery of filamentous fungi from water in a paediatric bone marrow transplantation unit. J. Hosp. Infect. 47: 143148.
121. Warris, A.,, C. H. Klaassen,, J. F. Meis,, M. T. De Ruiter,, H. A. De Valk,, T. G. Abrahamsen,, P. Gaustad, and, P. E. Verweij. 2003. Molecular epidemiology of Aspergillus fumigatus isolates recovered from water, air, and patients shows two clusters of genetically distinct strains. J. Clin. Microbiol. 41: 41014106.
122. Yeghen, T.,, C. C. Kibbler,, H. G. Prentice,, L. A. Berger,, R. K. Wal-lesby,, P. H. McWhinney,, F. C. Lampe, and, S. Gillespie. 2000. Management of invasive pulmonary aspergillosis in hematology patients: a review of 87 consecutive cases at a single institution. Clin. Infect. Dis. 31: 859868.
123. Zaoutis, T. E.,, K. Heydon,, J. H. Chu,, T. J. Walsh, and, W. J. Stein-bach. 2006. Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000. Pediatrics 117: e711e716.

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