Abstract
Advancements in diagnosis and the development of new effective agents have improved the response of invasive fungal infections to appropriate therapies, allowing an increasing number of patients with hematologic malignancies to complete chemotherapy or to be submitted to stem cell transplantation. Prophylaxis with a number of antifungal agents has resulted efficacy against the majority of species, although the lack of conclusive results makes antifungal prophylaxis different from Center to Center. Caspofungin has excellent activity against Candida and Aspergillus species and a safety profile with reduced toxicities compared to other antifungal agents, resulting in one of the most interesting drug for both prophylaxis and therapy. Relapse of invasive fungal infection, however, remains a marker of poor prognosis, especially for patients candidates to stem cell transplant, because of the related risk factors. In recent years, the concept of secondary prophylaxis has emerged for patients more at risk, confirming that a history of invasive fungal infection is not a contraindication for allogeneic transplantation and that secondary prophylaxis could effectively offer a low-risk transplant related mortality. Although limited, studies using Caspofungin as secondary prophylaxis have demonstrated that this approach is feasible and effective in preventing relapse of fungal infections, allowing patients to complete the appropriate therapeutic strategy.
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References
Allinson K, Kolve H, Gumbinger HG, Vormoor HJ, Ehlert K, Groll AH (2008) Secondary antifungal prophylaxis in paediatric allogeneic haematopoietic stem cell recipients. J Antimicrob Chemother 61:734–742
Bow EJ, Laverdière M, Lussier N, Rotstein C, Cheang MS, Ioannou S (2002) Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta analysis of randomized-controlled clinical trials. Cancer 94:3230–3324
Cattaneo C, Monte S, Algarotti A, Audisio E, Borlenghi E, Campiotti L, Cerqui E, Fanizza C, Giuliani R, Micò C, Rocconi R, Salvi A, Salvi F, Verga L, Levis A, Lambertenghi Deliliers G, Pogliani EM, Tognoni G, Rambaldi A, Rossi G (2011) A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study). J Antimicrob Chemother 66:2140–2145
Chou LS, Lewis RE, Ippoliti C, Champlin RE, Kontoyiannis DP (2007) Caspofungin as primary antifungal prophylaxis in stem cell transplant recipients. Pharmacotherapy 27:1644–1650
Cordonnier C, Rovira M, Maertens J, Olavarria E, Faucher C, Bilger K, Pigneux A, Cornely OA, Ullmann AJ, Bofarull RM, de la Cámara R, Weisser M, Liakopoulou E, Abecasis M, Heussel CP, Pineau M, Ljungman P, Einsele H (2010) Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study. Haematologica 95:1762–1768
Cornely O, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, Helfgott D, Holowiecki J, Stockelberg D, Goh YT, Petrini M, Hardalo C, Suresh R, Angulo-Gonzalez D (2007) Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 356:348–359
de Fabritiis P, Spagnoli A, Di Bartolomeo P, Locasciulli A, Cudillo L, Milone G, Busca A, Picardi A, Scimè R, Bonini A, Cupelli L, Chiusolo P, Olivieri A, Santarone S, Poidomani M, Fallani S, Novelli A, Majolino I (2007) Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection. Bone Marrow Transplant 40:245–249
De Pauw B, Donnelly P (2007) Prophylaxis and Aspergillosis. Has the principle been proved? N Eng J Med 356:409–411
El-Cheikh J, Castagna L, Wang L, Esterni B, Faucher C, Fürst S, Pierre B, Mohty M, Blaise D (2010) Impact of prior invasive aspergillosis on outcome in patients receiving reduced-intensity conditioning allogeneic hematopoietic stem cell transplant. Leuk Lymphoma 51:1705–1710
Fukuda T, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Martin PJ, Storb RF, Marr KA (2003) Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 102:827–833
Fukuda T, Boeckh M, Guthrie KA, Mattson DK, Owens S, Wald A, Sandmaier BM, Corey L, Storb RF, Marr KA (2004) Invasive aspergillosis before allogeneic hematopoietic stem cell transplantation: 10-year experience at a single transplant center. Biol Blood Marrow Transplant 10:494–503
Glasmacher A, Prentice A, Gorschlüter M, Engelhart S, Hahn C, Djulbegovic B, Schmidt-Wolf IG (2003) Itraconazole prevents invasive fungal infections in neutropenic patients treated for hematologic malignancies: evidence from a meta-analysis of 3,597 patients. J Clin Oncol 21:4615–4626
Glasmacher A, Cornely O, Ullmann AJ, Wedding U, Bodenstein H, Wandt H, Boewer C, Pasold R, Wolf HH, Hänel M, Dölken G, Junghanss C, Andreesen R, Bertz H, Itraconazole Research Group of Germany (2006) An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia. J Antimicrob Chemother 57:317–325
Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 326:845–851
Hamza NS, Ghannoum MA, Lazarus HM (2004) Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 34:377–389
Junghanss C, Marr KA, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Chauncey T, McSweeney PA, Storb R (2002) Incidence and outcome of bacterial and fungal infections following non-myeloablative compared to myeloablative allogeneic hematolopietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 8:512–520
Kanda Y, Yamamoto R, Chizuka A, Hamaki T, Suguro M, Arai C, Matsuyama T, Takezako N, Miwa A, Kern W, Kami M, Akiyama H, Hirai H, Togawa A (2000) Prophylactic action of oral fluconazole against fungal infection in neutropenic patients. A meta-analysis of 16 randomized, controlled trials. Cancer 89:1611–1625
Maertens J (2007) Evaluating prophylaxis of invasive fungal infections in patients with hematologic malignancies. Eur J Haematol 78:275–282
Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, Sable CA, Kartsonis NA, Ngai A, Taylor A, Patterson TF, Denning DW, Walsh TJ (2004) Efficacy and safety of Caspofungin for treatment of invasive aspergillosis in patientsa refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis 39:1563–1571
Martino R, Parody R, Fukuda T, Maertens J, Theunissen K, Ho A, Mufti GJ, Kroger N, Zander AR, Heim D, Paluszewska M, Selleslag D, Steinerova K, Ljungman P, Cesaro S, Nihtinen A, Cordonnier C, Vazquez L, López-Duarte M, Lopez J, Cabrera R, Rovira M, Neuburger S, Cornely O, Hunter AE, Marr KA, Dornbusch HJ, Einsele H (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 108:2928–2936
Mattiuzzi GN, Alvarado G, Giles FJ, Ostrosky-Zeichner L, Cortes J, O’brien S, Verstovsek S, Faderl S, Zhou X, Raad II, Bekele BN, Leitz GJ, Lopez-Roman I, Estey EH (2006) Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies. Antimicrob Agents Chemother 50:143–147
Mora-Duarte J, Betts R, Rotstein C, Colombo AL, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J, Caspofungin Invasive Candidiasis Study Group (2002) Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med 347:2020–2029
Nagappan V, Deresinski S (2007) Posaconazole: a broad spectrum triazole antifungal agent. Clin Infect Dis 45:1610–1617
Offner F, Cordonnier C, Ljungman P, Prentice HG, Engelhard D, De Bacquer D, Meunier F, De Pauw B (1998) Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis 26:1098–1103
Prentice AG, Glasmacher A, Djulbegovic B (2006) In meta-analysis itraconazole is superior to fluconazole for prophylaxis of systemic fungal infections in the treatment of haematological malignancy. Br J Haematol 132:656–658
Rijnders BJ, Cornelissen JJ, Slobbe L, Becke rMJ, Doorduijn JK, Hop WC, Ruijgrok EJ, Löwenberg B, Vulto A, Lugtenburg PJ, de Marie S (2008) Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: a randomized, placebo-controlled trial. Clin Infect Dis 46:1401–1408
Segal BH, Almyroudis NG, Battiwalla M, Herbrecht R, Perfect JR, Walsh TJ, Wingard JR (2007) Prevention and early treatment of invasive fungal infection in patients with cancer and neutropenia and in stem cell transplant recipients in the era of newer broad-spectrum antifungal agents and diagnostic adjuncts. Clin Infect Dis 44:402–409
Sipsas NV, Kontoyiannis DP (2006) Clinical issue regarding relapsing aspergillosis and the efficacy of secondary antifungal prophylaxis in patients with hematological malignancies. Clin Infect Dis 42:1584–1591
Vardakas K, Michalopoulos A, Falagas M (2005) Fluconazole versus Itraconazole for antifungal prophylaxis in neutropenic patients with haematological malignancies: a meta-analysis of randomized-controlled trials. Br J Haematol 131:22–28
Vehreschild JJ, Sieniawski M, Reuter S, Arenz D, Reichert D, Maertens J, Böhmef A, Silling G, Martino R, Maschmeyer G, Rüping MJGT, Ullmannj AJ, Cornely OA (2009) Efficacy of caspofungin and itraconazole as secondary antifungal prophylaxis: analysis of data from a multinational case registry. Int J Antimicrob Agents 34:446–450
Viollier AF, Peterson DE, De Jongh CA, Newman KA, Gray WC, Sutherland JC, Moody MA, Schimpff SC (1986) Aspergillus sinusitis in cancer patients. Cancer 58:366–371
Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, DePauw BE (2004) Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 351:1391–1402
Wingard JR (1999) Fungal infections after bone marrow transplant. Biol Blood Marrow Transplant 5:55–68
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de Fabritiis, P. (2013). Reduction in the Risk Invasive Fungal Infection Relapse in Patients Undergoing Allogenic Stem Cell Transplantation Using Caspofunginas Secondary Prophylaxis. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 10. Stem Cells and Cancer Stem Cells, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6262-6_23
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