Efficacy and safety of micafungin in unrelated cord blood transplant recipients
Micafungin (MCFG) is an echinocandin antifungal drug used for prophylaxis and treatment of fungal infections after allogeneic hematopoietic cell transplantation (HCT). However, its efficacy and safety in patients undergoing cord blood transplantation (CBT) has not been clarified. We retrospectively analyzed the efficacy and safety of MCFG in 92 adult patients undergoing CBT in our institute. Of the entire cohort, 83 patients (90%) received MCFG for empirical or preemptive therapy. Documented breakthrough fungal infection occurred in 2 patients during MCFG treatment. Among the 49 patients who received MCFG as empirical therapy for febrile neutropenia, 41 (84%) patients had resolution of fever during neutropenia. Elevation of serum levels of hepatobiliary parameters during MCFG treatment was commonly observed, but grade 3 or higher elevation was rare. We also compared the efficacy and safety of 2 different initial daily doses of MCFG (150 mg vs. 300 mg). There were no significant differences of efficacy and safety between the two groups. These data suggest that MCFG was effective and safe for adult patients undergoing CBT. The optimal daily dose of MCFG treatment is a matter of future investigation for adult patients undergoing CBT.
KeywordsMicafungin Cord blood transplantation Efficacy Adverse events Daily dose Echinocandin
The authors thank all of the physicians and staff at out hospital in this study.
Compliance with ethical standards
This case study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Conflict of interest
The authors declare that they have no conflicts of interest.
- 4.Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y, Yamada T, Uchimaru K, Tojo A, Shirafuji N, Kodo H, Tani K, Takahashi T, Yamaguchi T, Asano S (2004) Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies. Blood 104:3813–3820CrossRefGoogle Scholar
- 5.Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, Fukuno K, Uchiyama M, Takasugi K, Iseki T, Tojo A, Yamaguchi T, Asano S (2007) Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 109:1322–1330CrossRefGoogle Scholar
- 6.Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W, Sirvent A, Champlin RE, Chao N, Gee AP, Isola L, Laughlin MJ, Marks DI, Nabhan S, Ruggeri A, Soiffer R, Horowitz MM, Gluckman E, Wagner JE, Center for International Blood and Marrow Transplant Research; Acute Leukemia Working Party Eurocord (the European Group for Blood Marrow Transplantation); National Cord Blood Program of the New York Blood Center (2010) Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol 11:653–660CrossRefGoogle Scholar
- 7.Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, Najima Y, Fukuda T, Uchida N, Takahashi S, Nagamura-Inoue T, Morishima Y, Miyamura K, Japan Society for Hematopoietic Cell Transplantation (2016) Comparison of outcomes of 8/8 and 7/8 allele-matched unrelated bone marrow transplantation and single-unit cord blood transplantation in adults with acute leukemia. Biol Blood Marrow Transplant 22:330–338CrossRefGoogle Scholar
- 8.Konuma T, Tsukada N, Kanda J, Uchida N, Ohno Y, Miyakoshi S, Kanamori H, Hidaka M, Sakura T, Onizuka M, Kobayashi N, Sawa M, Eto T, Matsuhashi Y, Kato K, Ichinohe T, Atsuta Y, Miyamura K, Donor/Source Working Group of the Japan Society for Hematopoietic Cell Transplantation (2016) Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older. Am J Hematol 91:E284–E292CrossRefGoogle Scholar
- 9.Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, Pecoraro C, Guidi S, Iori AP, Montante B, Chiusolo P, Lanino E, Carella AM, Zucchetti E, Bruno B, Irrera G, Patriarca F, Baronciani D, Musso M, Prete A, Risitano AM, Russo D, Mordini N, Pastore D, Vacca A, Onida F, Falcioni S, Pisapia G, Milone G, Vallisa D, Olivieri A, Bonini A, Castagnola E, Sica S, Majolino I, Bosi A, Busca A, Arcese W, Bandini G, Bacigalupo A, Rambaldi A, Locasciulli A (2014) Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant 20:872–880CrossRefGoogle Scholar
- 10.Choi JK, Cho SY, Yoon SS, Moon JH, Kim SH, Lee JH, Kim JS, Cheong JW, Jang JH, Seo BJ, Kim YJ, Lee HJ, Lee J, Lee JW, Lee DG (2017) Epidemiology and risk factors for invasive fungal diseases among allogeneic hematopoietic stem cell transplant recipients in Korea: results of “RISK” study. Biol Blood Marrow Transplant 23:1773–1779CrossRefGoogle Scholar
- 11.van Burik JA, Ratanatharathorn V, Stepan DE, Miller CB, Lipton JH, Vesole DH, Bunin N, Wall DA, Hiemenz JW, Satoi Y, Lee JM, Walsh TJ, National Institute of Allergy and Infectious Diseases Mycoses Study Group (2004) Micafungin versus fluconazole for prophylaxis against invasive fungal infections during neutropenia in patients undergoing hematopoietic stem cell transplantation. Clin Infect Dis 39:1407–1416CrossRefGoogle Scholar
- 12.Sirohi B, Powles RL, Chopra R, Russell N, Byrne JL, Prentice HG, Potter M, Koblinger S (2006) A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation. Bone Marrow Transplant 38:47–51CrossRefGoogle Scholar
- 13.Hashino S, Morita L, Takahata M, Onozawa M, Nakagawa M, Kawamura T, Fujisawa F, Kahata K, Izumiyama K, Yonezumi M, Chiba K, Kondo T, Asaka M (2008) Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation. Int J Hematol 87:91–97CrossRefGoogle Scholar
- 14.Hiramatsu Y, Maeda Y, Fujii N, Saito T, Nawa Y, Hara M, Yano T, Asakura S, Sunami K, Tabayashi T, Miyata A, Matsuoka KI, Shinagawa K, Ikeda K, Matsuo K, Tanimoto M, West-Japan Hematology and Oncology Group (West-JHOG) (2008) Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation. Int J Hematol 88:588–595CrossRefGoogle Scholar
- 16.Park S, Kim K, Jang JH, Kim SJ, Kim WS, Chung DR, Kang CI, Peck KR, Jung CW (2016) Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients. J Inf Secur 73:496–505Google Scholar
- 19.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 351:1391–1402CrossRefGoogle Scholar
- 20.De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Muñoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE, European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group (2008) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 46:1813–1821CrossRefGoogle Scholar
- 22.Lee CH, Lin JC, Ho CL, Sun M, Yen WT, Lin C (2017) Efficacy and safety of micafungin versus extensive azoles in the prevention and treatment of invasive fungal infections for neutropenia patients with hematological malignancies: a meta-analysis of randomized controlled trials. PLoS One 12:e0180050CrossRefGoogle Scholar
- 23.Jeong SH, Kim DY, Jang JH, Mun YC, Choi CW, Kim SH, Kim JS, Park JS (2016) Efficacy and safety of micafungin versus intravenous itraconazole as empirical antifungal therapy for febrile neutropenic patients with hematological malignancies: a randomized, controlled, prospective, multicenter study. Ann Hematol 95:337–344CrossRefGoogle Scholar
- 27.Kishi Y, Kami M, Miyakoshi S, Kanda Y, Murashige N, Teshima T, Kusumi E, Hara S, Matsumura T, Yuji K, Masuoka K, Wake A, Morinaga S, Kanemaru M, Hayashi T, Tanaka Y, Taniguchi S, Tokyo Stem Cell Transplant Consortium (2005) Early immune reaction after reduced-intensity cord-blood transplantation for adult patients. Transplantation 80:34–40CrossRefGoogle Scholar
- 29.Konuma T, Takahashi S, Kiyuna T, Miharu Y, Suzuki M, Shibata H, Kato S, Takahashi S, Tojo A (2017) Breakthrough fungemia due to Candida fermentati with fks1p mutation under micafungin treatment in a cord blood transplant recipient. Transpl Infect Dis 19Google Scholar
- 30.Kimura M, Araoka H, Yamamoto H, Asano-Mori Y, Nakamura S, Yamagoe S, Ohno H, Miyazaki Y, Abe M, Yuasa M, Kaji D, Kageyama K, Nishida A, Ishiwata K, Takagi S, Yamamoto G, Uchida N, Izutsu K, Wake A, Taniguchi S, Yoneyama A (2017) Clinical and microbiological characteristics of breakthrough candidemia in allogeneic hematopoietic stem cell transplant recipients in a Japanese hospital. Antimicrob Agents Chemother 61:e01791–e01716Google Scholar
- 34.Heimann SM, Vehreschild MJ, Meintker L, Heinz W, Schroeder T, von Bergwelt-Baildon M, Cornely OA, Vehreschild JJ (2014) Different doses of micafungin for prophylaxis of invasive fungal diseases in hemato-oncological high-risk patients: a web-based non-interventional trial in four large university hospitals in Germany. Transpl Infect Dis 16:968–974CrossRefGoogle Scholar
- 35.Cordonnier C, Pautas C, Maury S, Vekhoff A, Farhat H, Suarez F, Dhédin N, Isnard F, Ades L, Kuhnowski F, Foulet F, Kuentz M, Maison P, Bretagne S, Schwarzinger M (2009) Empirical versus preemptive antifungal therapy for high-risk, febrile, neutropenic patients: a randomized, controlled trial. Clin Infect Dis 48:1042–1051CrossRefGoogle Scholar
- 36.Servais S, Lengline E, Porcher R, Carmagnat M, Peffault de Latour R, Robin M, Sicre de Fontebrune F, Clave E, Maki G, Granier C, Xhaard A, Dhedin N, Molina JM, Toubert A, Moins-Teisserenc H, Socie G (2014) Long-term immune reconstitution and infection burden after mismatched hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 20:507–517CrossRefGoogle Scholar