A review of infectious complications after haploidentical hematopoietic stem cell transplantations



Allogeneic hematopoietic stem cell transplantation from haploidentical donor is a feasible option for patients with hematological diseases who lack a suitable HLA-matched donor, but viral and fungal infections are still the most common causes of morbidity and mortality in haploidentical transplantation setting because of delayed immune reconstitution, increased risk of graft vs host disease (GvHD) or systemic steroid use. Therefore, this review will focus on the infectious complications after haploidentical hematopoietic stem cell transplantation (HSCT).

Materials and methods

Electronic publications were searched until February 2017 throughout databases, including Pubmed, Cochrane, and Embase. The following keywords were used ‘haploidentical transplantation’, ‘infection’, ‘T cell replete’, and ‘T cell deplete’.


An increased incidence of bacterial, fungal, or viral infections is detected in haplo-HSCT compared to related, unrelated, or cord blood transplantations. Neutropenia and use of systemic steroid for GvHD and delayed immune reconstitution are important risk factors for infection after haplo-HSCT.


A shift towards T cell repletes haplo-HSCT with post-transplant cyclophosphamide (CY) for GvHD has been emerged in recent years, in which the incidence of viral and fungal infections is detected to be lower. Prophylaxis and pre-emptive treatment strategies should be applied according to patient status.

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Fig. 1


  1. 1.

    Kroger N, Damon L, Zander AR, Wandt H, Derings G, Ferrante P, Demirer T, Rosti G, European Group Blood Marrow Transplantation, German Adjuvant Breast Cancer Study, University of California San Francisco. Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patient. Bone Marrow Transpl. 2003;32:1153–7.

    CAS  Article  Google Scholar 

  2. 2.

    De Giorgi U, Rosti G, Slavin S, Yaniv I, Harousseau JL, Ladenstein R, Demirer T, Dini G, European Group Blood Marrow Transplantation. Salvage high-dose chemotherapy for children with extragonadal germ-cell tumours. Br J Cancer. 2005;93:412–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Pedrazzoli P, Ferrante P, Kulekci A, Schiavo R, De Giorgi U, Carminato O, Marangolo M, Demirer T, Sienna S, Rosti G. Autologous hematopoietic stem cell transplantation for breast cancer in Europe: critical evaluation of data from the European Group for Blood and Marrow Transplantation (EBMT) Registry 1990–1999. Bone Marrow Transpl. 2003;32:489–94.

    CAS  Article  Google Scholar 

  4. 4.

    Pedrazzoli P, Ledermann JA, Lotz J-P, Leyvraz S, Aglietta M, Rosti G, Champion KM, Secondino S, Selle F, Ketterer N, Grignani G, Siena S, Demirer T, European Group Blood Marrow Transplantation. High dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol. 2006;17:1479–88.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Demirer T, Gooley T, Buckner CD, Petersen FB, Lilleby K, Rowley S, Sanders J, Storb R, Appelbaum FR, Bensinger WI. Influence of total nucleated cell dose from marrow harvests on outcome in patients with acute myelogenous leukemia undergoing autologous transplantation. Bone Marrow Transpl. 1995;15:907–13.

    CAS  Google Scholar 

  6. 6.

    Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Smith DA, Yancey LJ, Crump M, Stadtmauer EA, Biron P, Crown JP, Schmid P, Lotz JP, Rosti G, Bregni M, Demirer T. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol. 2011;29:3224–31.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    De Giorgi U, Demirer T, Wandt H, Taverna C, Siegert W, Bornhauser M, Kozak T, Papiani G, Ballardini M, Rosti G. Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience. Ann Oncol. 2005;16:146–51.

    Article  PubMed  Google Scholar 

  8. 8.

    Holmberg LA, Demirer T, Rowley S, Buckner CD, Goodman G, Maziarz R, Klarnet J, Zuckerman N, Harrer G, McCloskey R, Gersh R, Goldberg R, Nichols W, Jacobs A, Weiden P, Montgomery P, Rivkin S, Appelbaum FR, Besinger WI. High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III–IV ovarian cancer. Bone Marrow Transpl. 1998;22:651–9.

    CAS  Article  Google Scholar 

  9. 9.

    Reisner Y, Aversa F, Martelli MF. Haploidentical hematopoietic stem cell transplantation: state of art. Bone Marrow Transpl. 2015;50:S1–5.

    Article  Google Scholar 

  10. 10.

    Peccatori J, Barkholt L, Demirer T, Sormani MP, Bruzzi P, Ciceri F, Zambelli A, Da Prada GA, Pedrazzoli P, Siena S, Massenkeil G, Martino R, Lenhoff S, Corradini P, Rosti G, Ringden O, Bregni M, Niederwiesser D, on behalf of EBMT. Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation. Cancer. 2005;104:2099–103.

    Article  PubMed  Google Scholar 

  11. 11.

    Demirer T, Celebi H, Arat M, Ustun C, Demirer S, Dilek I, Ozcan M, Ilhan O, Akan H, Gurman G, Koc H. Autoimmune thrombocytopenia in a patient with small cell lung cancer developing after chemotherapy and resolving following autologous peripheral blood stem cell transplantation. Bone Marrow Transpl. 1999;24:335–7.

    CAS  Article  Google Scholar 

  12. 12.

    Secondino S, Carrabba MG, Pedrazzoli P, Castagna L, Spina F, Grosso F, Bertuzzi A, Bay JO, Siena S, Corradini P, Niederwieser D, Demirer T. Reducued intensity stem cell transplantation for advanced soft tissue sarcomas in adults: a retrospective analysis of the European Group for Blood and Marrow Transplantation. Haematologica. 2007;92:418–20.

    Article  PubMed  Google Scholar 

  13. 13.

    Aglietta M, Barkholt L, Schianca FC, Caravelli D, Omazic B, Minotto C, Leone F, Hentschke P, Bertoldero G, Capaldi A, Ciccone G, Niederwieser D, Ringden O, Demirer T, On behalf of the EBMT Solid Tumor Working Party. Reduced intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. the european group for blood and marrow transplantation experience. Biol Blood Marrow Transpl. 2009;15:326–35.

    CAS  Article  Google Scholar 

  14. 14.

    Bensinger WI, Demirer T, Buckner CD, Appelbaum FR, Storb R, Lilleby K, Weiden P, Bluming AZ, Fefer A. Syngeneic marrow transplantation in patients with multiple myeloma. Bone Marrow Transpl. 1996;18:527–31.

    CAS  Google Scholar 

  15. 15.

    Raiola AM, Dominietto A, Di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, Bacigalupo A. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transpl. 2014;20:1573–9.

    Article  Google Scholar 

  16. 16.

    Long H, Lu ZG, Song CY, Huang YX, Xu JH, Xu JX, Deng L, Tu SF, He YZ, Lin X, Guo KY, Wu BY. Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies. Bone Marrow Transpl. 2016;51:1470–5.

    CAS  Article  Google Scholar 

  17. 17.

    Demirer T, Buckner CD, Appelbaum FR, Besinger WI, Sanders J, Lambert K, Clift R, Fefer A, Storb R, Slattery JT. Busulfan, cyclophosphamide and fractionated total body irradiation for autologous or syngeneic marrow transplantation for acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels. Bone Marrow Transpl. 1996;17:491–5.

    CAS  Google Scholar 

  18. 18.

    Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, Morris LE, Holland HK, Solomon SR. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and hla-identical sibling donors: a multivariable analysis including disease risk index. Biol Blood Marrow Transpl. 2016;22:125–33.

    CAS  Article  Google Scholar 

  19. 19.

    Sun Y, Beohou E, Labopin M, Volin L, Milpied N, Yakoub-Agha I, Piemontese S, Polge E, Houhou M, Huang XJ, Mothy M, Nagler A, Gorin NC. Unmanipulated haploidentical versus matched unrelated donor allogeneic stem cell transplantation in adult patients with acute myelogenous leukemia in first remission: a retrospective pair-matched comparative study of the Beijing approach with the EBMT data base. Haematologica. 2016;101:e352–4.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Chang YJ, Zhao XY, Xu LP, Liu DH, Liu KY, Chen YH, Wang Y, Zhang XH, Zhao XS, Han W, Chen H, Wang FR, Lv M, Huang XJ. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome. Leuk Lymphoma. 2013;54:2671–7.

    Article  PubMed  Google Scholar 

  21. 21.

    Ciurea SO, Mulanovich V, Jiang Y, Bassett R, Rondon G, McMannis J, de Lima M, Shpall EJ, Champlin RE. Lymphocyte recovery predicts outcomes in cord blood and T cell-depleted haploidentical stem cell transplantation. Biol Blood Marrow Transpl. 2011;17:1169–75.

    Article  Google Scholar 

  22. 22.

    Chang YJ, Zhao XY, Huo MR, Xu LP, Liu DH, Liu KY, Huang XJ. Immune reconstitution following unmanipulated HLA-mismatched/haploidentical transplantation compared with HLA-identical sibling transplantation. J Clin Immunol. 2012;32:268–80.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Dominietto A, Raiola AM, Bruno B, Lint MT, Francesco F, Grazia CD, Gualandi F, Bregante S, Varaldo R, Ghiso A, Bacigalupo A. Rapid immune reconstitution following unmanipulated haploidentical BMT with post-transplant high-dose cyclophosphamide ASH Annual Meeting Abstracts. Blood. 2011;118:3050.

    Google Scholar 

  24. 24.

    Chang Ying-Jun, Zhao Xiao-Yu, Huang Xiao-Jun. Immune reconstitution after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:440–9.

    CAS  Article  Google Scholar 

  25. 25.

    Chang Y-J, Zhao X-Y, Huang X-J. Effects of the NK cell recovery on outcomes of unmanipulated haploidentical blood and marrow transplantation for patients with hematologic malignancies. Biol Blood Marrow Transpl. 2008;14:323–34.

    Article  Google Scholar 

  26. 26.

    Chang YJ, Zhao XY, Huang XJ. Immune reconstitution after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:440–9.

    CAS  Article  Google Scholar 

  27. 27.

    Demirer T, Petersen FB, Bensinger WI, Appelbaum FR, Fefer A, Rowley S, Sanders J, Chauncey T, Storb R, Lilleby K, Buckner CD. Autologous transplantation with peripheral blood stem cells collected after granulocyte colony-stimulating factor in patients with acute myelogenous leukemia. Bone Marrow Transpl. 1996;18:29–34.

    CAS  Google Scholar 

  28. 28.

    Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013;31:1310–6.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Sun YQ, Huang XJ. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer. 2013;119:978–85.

    Article  PubMed  Google Scholar 

  30. 30.

    Aversa F, Velardi A, Tabilio A, Reiner Y, Martelli MF. Haploidentical stem cell transplantation in leukemia. Blood Rev. 2001;15:111–9.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989;320:197–204.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Brunvand MW, Bensinger WI, Soll E, Weaver CH, Rowley SD, Appelbaum FR, Lilleby K, Clift RA, Gooley TA, Press OW, Fefer A, Storb R, Sanders JE, Martin PL, Chauncey T, Maziarz RT, Zuckerman N, Montgomery P, Dorn R, Wieden PL, Demirer T, Holmberg LA, Schiffman K, McSweeney PA, Buckner CD. High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells. Bone Marrow Transpl. 1996;18:131–41.

    CAS  Google Scholar 

  33. 33.

    Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, Tordato F, Mauro E, Timofeeva I, Lugli E, Mavilio D, Carlo-Stella C, Santoro A, Castagna L. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17:242–9.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Meunier F, Lukan C. The First European Conference on Infections in Leukaemia—ECIL1: a current perspective. Eur J Cancer. 2008;44:2112–7.

    Article  PubMed  Google Scholar 

  35. 35.

    Young JA, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, Knust K, Horowitz MM, Confer DL, Dubberke ER, Pergam SA, Marty FM, Strasfeld LM, Brown JW, Langston AA, Schuster MG, Kaul DR, Martin SI, Anasetti C. Infections after transplantation of bone marrow or peripheral blood stem cells from unrelated donors. Biol Blood Marrow Transpl. 2016;22:359–70.

    Article  Google Scholar 

  36. 36.

    Perez-Simon JA, Garcia-Escobar I, Martinez J, Vazquez L, Caballero D, Canizo C, Mateos MV, San Miguel JF. Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation. Bone Marrow Transpl. 2004;33:183–7.

    CAS  Article  Google Scholar 

  37. 37.

    Fuji S, Kapp M, Einsele H. Possible implication of bacterial infection in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Front Oncol. 2014;24:89.

    Google Scholar 

  38. 38.

    Fuji S, Kim SW, Fukuda T, Mori S, Yamasaki S, Morita-Hoshi Y, Ohara-Waki F, Heike Y, Tobinai K, Tanosaki R, Takaue Y. Preengraftment serum C-reactive protein (CRP) value may predict acute graft-versus-host disease and nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2008;14:510–7.

    CAS  Article  Google Scholar 

  39. 39.

    Shono Y, Docampo MD, Peled JU, Perobelli SM, Velardi E, Tsai JJ, Slingerland AE, Smith OM, Young LF, Gupta J, Lieberman SR, Jay HV, Ahr KF, Porosnicu Rodriguez KA, Xu K, Calarfiore M, Poeck H, Caballero S, Devlin SM, Rapaport F, Dudakov JA, Hanash AM, Gyurkocza B, Murphy GF, Gomes C, Liu C, Moss EL, Falconer SB, Bhatt AS, Taur Y, Pamer EG, Van den Brink MR, Jenq RR. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice. Sci Transl Med. 2016;8:339ra71.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, Zhu W, Sporrer D, Hehlgans T, Kreutz M, Holler B, Wolff D, Edinger M, Andreesen R, Levine JE, Ferrara JL, Gessner A, Spang R, Oefner PJ. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transpl. 2014;20:640–5.

    Article  Google Scholar 

  41. 41.

    Demirer T, Buckner CD, Appelbaum FR, Clift R, Storb R, Myerson D, Lilleby K, Rowley S, Bensinger WI. High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer. Bone Marrow Transpl. 1996;17:769–74.

    CAS  Google Scholar 

  42. 42.

    Lehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, Hakim H, Santolaya M, Castagnola E, Davis BL, Dupuis LL, Gibson F, Groll F, Groll AH, Gaur A, Gupta A, Kebudi R, Petrilli S, Steinbach WJ, Villarroel M, Zaoutis T, Sung L. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012;30:4427–38.

    Article  PubMed  Google Scholar 

  43. 43.

    Scholl S, Hanke M, Hoffken K, Sayer HG. Distinct reconstitution of neutrophil functions after allogeneic peripheral blood stem cell transplantation. J Cancer Res Clin Oncol. 2007;133:411–5.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Ramaprasad C, Pouch S, Pitrak DL. Neutrophil function after bone marrow and hematopoietic stem cell transplant. Leuk Lymphoma. 2010;51:756–67.

    Article  PubMed  Google Scholar 

  45. 45.

    Demirer T, Buckner CD, Appelbaum FR, Lambert K, Bensinger WI, Clift R, Storb P, Slattery JT. Busulfan, cyclophosphamide and fractionated total body irradiation for allogeneic marrow transplantation in advanced acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels. Bone Marrow Transpl. 1996;17:341–6.

    CAS  Google Scholar 

  46. 46.

    Capsoni F, Meroni PL, Zocchi MR, Plebani AM, Vezio M. Effect of corticosteroids on neutrophil function: inhibition of antibody-dependent cell mediated cytotoxicity (ADCC). J Immunopharmacol. 1983;5:217–30.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Ignarro LJ, Cech SY. Lysosomal enzyme secretion from human neutrophils mediated by cyclic CMP: inhibition of cyclic GMP accumulation and neutrophil function by glucocorticosteroids. J Cyclic Nucleotide Res. 1975;1:283–92.

    CAS  PubMed  Google Scholar 

  48. 48.

    Fuji S, Einsele H, Savani BN, Kapp M. Systematic nutritional support in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transpl. 2015;21:1707–13.

    Article  Google Scholar 

  49. 49.

    Fuji S, Rovo A, Ohashi K, Griffith M, Einsele H, Kapp M, Mothy M, Majhail NS, Engelhardt BG, Tichelli A, Savani BN. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT. Bone Marrow Transpl. 2016;51:1041–9.

    CAS  Article  Google Scholar 

  50. 50.

    Ueno NT, Rizzo D, Demirer T, Cheng YC, Hegenbart U, Zhang MJ, Bregni M, Carella A, Blaise D, Bashey A, Bitran JD, Bolwell BJ, Elgenbein GJ, Fields KK, Freytes CO, Gale RP, Lazarus HM, Champlin RE, Stiff PJ, Niederwieser D. Allogeneic hematopoietic cell transplantation for metastatic breast cancer. Bone Marrow Transpl. 2008;41:537–45.

    CAS  Article  Google Scholar 

  51. 51.

    Carpenter PA, Kitko CL, Elad S, Flowers ME, Gea-Banacloche JC, Halter JP, Hoodin F, Johnston L, Lawitschka A, McDonald GB, Opipari AW, Savani BN, Schultz KR, Smith SR, Syrjala KL, Treister N, Vogelsang GB, Williams KM, Pavletic SZ, Martin PJ, Lee SJ, Couriel DR. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: V. The 2014 ancillary therapy and supportive care working group report. Biol Blood Marrow Transpl. 2015;21:1167–87.

    Article  Google Scholar 

  52. 52.

    Fuji S, Kapp M, Einsele H. Challenges to preventing infectious complications, decreasing re-hospitalizations, and reducing cost burden in long-term survivors after allogeneic hematopoietic stem cell transplantation. Semin Hematol. 2012;49:10–4.

    Article  PubMed  Google Scholar 

  53. 53.

    Ullmann AJ, Schmidt-Hieber M, Bertz H, Heinz WJ, Kiehl M, Kruger W, Mousset S, Neuburger S, Neumann S, Penack O, Silling G, Vehreschild JJ, Einsele H, Maschmeyer G. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol. 2016;95:1435–55.

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transpl. 2009;15:1143–238.

    CAS  Article  Google Scholar 

  55. 55.

    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, Irrrera G, Patriarca E, 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. 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 Transpl. 2014;20:872–80.

    Article  Google Scholar 

  56. 56.

    Fleming S, Yannakou CK, Haeusler GM, Clark J, Grigg A, Heath CH, Bajel A, van Hal SJ, Chen SC, Miliken ST, Morrissey CO, Tam CS, Szer J, Weinkove R, Slavin MA. Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014. Intern Med J. 2014;44:1283–97.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    Sun YQ, Xu LP, Liu DH, Zhang XH, Chen YH, Chen H, Ji Y, Wang Y, Han W, Wang JZ, Wang FR, Liu KY, Huang XJ. The incidence and risk factors of invasive fungal infection after haploidentical haematopoietic stem cell transplantation without in vitro T-cell depletion. Clin Microbiol Infect. 2012;18:997–1003.

    Article  PubMed  Google Scholar 

  58. 58.

    Sun Y, Xu L, Liu D, Zhang X, Han W, Wang Y, Chen H, Chen Y, Wang F, Wang J, Ji Y, Tang F, Liu K, Huang XJ. Incidence of invasive fungal disease after unmanipulated haploidentical stem cell transplantation was significantly higher than that after HLA-matched sibling transplantation. Clin Microbiol Infect. 2013;19:1029–34.

    CAS  Article  PubMed  Google Scholar 

  59. 59.

    Sahin U, Toprak SK, Atilla PA, Atilla E, Demirer T. An overview of infectious complications after allogneic hematopoietic stem cell transplantation. J Infect Chemother. 2016;22:505–14.

    Article  PubMed  Google Scholar 

  60. 60.

    Omer AK, Ziakas PD, Anagnostou T, Coughlin E, Kourkoumpetis T, McAfee SL, Dey BR, Attar E, Chen YB, Spitzer TR, Mylonakis E, Ballen KK. Risk factors for invasive fungal disease after allogeneic hematopoietic stem cell transplantation: a single center experience. Biol Blood Marrow Transpl. 2013;19:1190–6.

    Article  Google Scholar 

  61. 61.

    Hassler A, Lieb A, Seidel D, Cesaro S, Greil J, Klimko N, Khostelidi S, Solopova G, Ogunc D, Duran Graeff L, Cornely OA, Vehreschild M, Lehrnbecher T. Disseminated fusariosis in immunocompromised children—Analysis of Recent Cases Identified in the Global Fungiscope Registry. Pediatr Infect Dis J. 2017;36:230–1.

    Article  PubMed  Google Scholar 

  62. 62.

    Ziakas PD, Kourbeti IS, Mylonakis E. Systemic antifungal prophylaxis after hematopoietic stem cell transplantation: a meta-analysis. Clin Ther. 2014;36:292–306.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Bow EJ, Vanness DJ, Slavin M, Cordonnier C, Cornely OA, Marks DI, Pagliuca A, Solano C, Cragin L, Shaul AJ, Sorensen S, Chambers R, Kantecki M, Weinstein D, Schlamm H. Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. BMC Infect Dis. 2015;17:128.

    Article  Google Scholar 

  64. 64.

    Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, Roilides E, Styczynski J, Warris A, Lehrnbecher T. Fourth european conference on infections in leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15:e327–40.

    Article  PubMed  Google Scholar 

  65. 65.

    Tischer J, Engel N, Fritsch S, Prevalsek D, Hubmann M, Schulz C, Zoellner AK, Bucklein V, Reibke R, Mumm F, Rieger CT, Hill W, Ledderose G, Stemmler HJ, Kohnke T, Jager G, Kolb HJ, Schmid C, Moosmann A, Hausmann A. Virus infection in HLA-haploidentical hematopoietic stem cell transplantation: incidence in the context of immune recovery in two different transplantation settings. Ann Hematol. 2015;94:1677–88.

    CAS  Article  PubMed  Google Scholar 

  66. 66.

    Di Stasi A, Milton DR, Poon LM, Hamdi A, Rondon G, Chen J, Pingali SR, Konopleva M, Kongtim P, Alousi A, Qazilbash MH, Ahmed S, Bashir Q, Al-atrash G, Oran B, Hosing CM, Kebriaei P, Popat U, Shpall EJ, Lee DA, de Lima M, Rezvani K, Khouri IF, Champlin RE, Ciurea SO. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transpl. 2014;20:1975–81.

    Article  Google Scholar 

  67. 67.

    Silva Lde P, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J, Han XY, Tarrand J, Ribeiro R, Gulbis A, Shpall EJ, Jones R, Popat U, Walker JA, Petropoulos D, Chiattone A, Stewart J, El-Zimaity M, Anderlini P, Giralt S, Champlin RE, de Lima M. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95:1183–90.

    Article  PubMed  Google Scholar 

  68. 68.

    El-Zimaity M, Saliba R, Chan K, Shahjahan M, Carrasco A, Khorshid O, Caldera H, Couriel D, Giralt S, Khouri I, Ippoliti C, Champlin R, de Lima M. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: donor type matters. Blood. 2004;103:4674–80.

    CAS  Article  PubMed  Google Scholar 

  69. 69.

    Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, Wang SA, Konopleva M, Fernandez-Vina M, Montes N, Bosque D, Chen J, Rondon G, Alatrash G, Alousi A, Bashir Q, Korbling M, Qazilbash M, Parmar S, Shpall E, Nieto Y, Hosing C, Kebriaei P, Khouri I, Popat U, de Lima M, Champlin RE. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2012;18:1835–44.

    Article  Google Scholar 

  70. 70.

    Moiseev IS, Pirogova OV, Alyanski AL, Babensko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bondarenko SN, Afanasyev BV. Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Transpl. 2016;22:1037–42.

    CAS  Article  Google Scholar 

  71. 71.

    Razonable RR. Management strategies for cytomegalovirus infection and disease in solid organ transplant recipients. Infect Dis Clin North Am. 2013;27:317–42.

    Article  PubMed  Google Scholar 

  72. 72.

    Green ML, Leisenring W, Stachel D, Pergam SA, Sandmaier BM, Wald A, Corey L, Boeckh M. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2012;18:1687–99.

    Article  Google Scholar 

  73. 73.

    Saral R, Ambinder RF, Burns WH, Angelopulos CM, Griffin DE, Burke PJ, Lietman PS. Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study. Ann Intern Med. 1983;99:773–6.

    CAS  Article  PubMed  Google Scholar 

  74. 74.

    Saral R, Burns WH, Laskin OL, Santos GW, Lietman PS. Acyclovir prophylaxis of herpes-simplex-virus infections. N Engl J Med. 1981;305:63–7.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Boeckh M, Nichols WG, Chemaly RF, Papanicolaou GA, Wingard JR, Xie H, Syrjala KL, Flowers ME, Stevens-Ayers T, Jerome KR, Leisenring W. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med. 2015;162:1–10.

    Article  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, Kolling K, Stobernack HP, Lischka P, Zimmermann H, Rubsamen-Schaeff H, Champlin RE, Ehninger G. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370:1781–9.

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010;116:5476–85.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irridation, and posttransplantion cyclophosphamide. Blood. 2001;98:3456–64.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D, Stevens-Ayers T, Flowers ME, Cunningham T, Corey L. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2003;101:407–14.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez AC, Malard F, Gomez A, Brissot E, Belhocine R, Vekhoff A, Lapusan S, Isnard F, Legrand O, Gozlan J, Boutolleau D, Ledraa T, Labopin M, Rubio MT, Mohty M. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17:822–30.

    CAS  Article  PubMed  Google Scholar 

  81. 81.

    Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transpl. 2012;18:1859–66.

    Article  Google Scholar 

  82. 82.

    Mulanovich VE, Jiang Y, de Lima M, Shpall EJ, Champlin RE, Ciurea SO. Infectious complications in cord blood and T-cell depleted haploidentical stem cell transplantation. Am J Blood Res. 2011;1:98–105.

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Taniguchi K, Yoshihara S, Tamaki H, Fujimoto T, Ikegame K, Kaida K, Nakata J, Inoue T, Kato R, Fujioka T, Okada M, Soma T, Ogawa H. Incidence and treatment strategy for disseminated adenovirus disease after haploidentical stem cell transplantation. Ann Hematol. 2012;91:1305–12.

    CAS  Article  PubMed  Google Scholar 

  84. 84.

    Pirsch JD, Maki DG. Infectious complications in adults with bone marrow transplantation and T-cell depletion of donor marrow. Increased susceptibility to fungal infections. Ann Intern Med. 1986;104:619–31.

    CAS  Article  PubMed  Google Scholar 

  85. 85.

    Girmenia C, Ferretti A, Barberi W. Epidemiology and risk factors for invasive fungal diseases in hematopoietic stem cell transplantation. Curr Opin Hematol. 2014;21:459–65.

    Article  PubMed  Google Scholar 

  86. 86.

    Gratwohl A, Baldomero H, Demirer T, Rosti G, Dini G, Ladenstein R, Urbano-Ispizua A. Hematopoetic stem cell transplantation for solid tumors in Europe. EBMT; STWP; PDWP. Ann Oncol. 2004;15:653–60.

    CAS  Article  PubMed  Google Scholar 

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All authors contributed equally to this review.

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Correspondence to Taner Demirer.

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Atilla, E., Atilla, P.A., Bozdağ, S.C. et al. A review of infectious complications after haploidentical hematopoietic stem cell transplantations. Infection 45, 403–411 (2017). https://doi.org/10.1007/s15010-017-1016-1

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  • Infections
  • Haploidentical hematopoietic stem cell transplantation
  • Bacterial
  • Viral
  • Fungal