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Erschienen in: Annals of Hematology 2/2024

06.11.2023 | Original Article

Non-viral pathogens of infectious diarrhoea post-allogeneic stem cell transplantation are associated with graft-versus-host disease

Erschienen in: Annals of Hematology | Ausgabe 2/2024

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Abstract

Infectious diarrhoea is common post-allogeneic haematopoietic stem-cell transplantation (alloHSCT). While the epidemiology of Clostridioides difficile infection (CDI) post-alloHSCT has been described, the impact of other diarrhoeal pathogens is uncertain. We reviewed all alloHSCT between 2017 and 2022 at a single large transplant centre; 374 patients were identified and included. The 1-year incidence of infectious diarrhoea was 23%, divided into viral (13/374, 3%), CDI (65/374, 17%) and other bacterial infections (16/374, 4%). There was a significant association between infectious diarrhoea within 1 year post-transplant and the occurrence of severe acute lower gastrointestinal graft-versus-host disease (GVHD, OR = 4.64, 95% CI 2.57–8.38, p < 0.001) and inferior GVHD-free, relapse-free survival on analysis adjusted for age, donor type, stem cell source and T-cell depletion (aHR = 1.64, 95% CI = 1.18–2.27, p = 0.003). When the classes of infectious diarrhoea were compared to no infection, bacterial (OR = 6.38, 95% CI 1.90–21.40, p = 0.003), CDI (OR = 3.80, 95% CI 1.91–7.53, p < 0.001) and multiple infections (OR = 11.16, 95% CI 2.84–43.92, p < 0.001) were all independently associated with a higher risk of severe GI GVHD. Conversely, viral infections were not (OR = 2.98, 95% CI 0.57–15.43, p = 0.20). Non-viral infectious diarrhoea is significantly associated with the development of GVHD. Research to examine whether the prevention of infectious diarrhoea via infection control measures or modulation of the microbiome reduces the incidence of GVHD is needed.
Literatur
1.
Zurück zum Zitat Kolb HJ, Mittermüller J, Clemm C, Holler E, Ledderose G, Brehm G, Heim M, Wilmanns W (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76(12):2462–2465CrossRefPubMed Kolb HJ, Mittermüller J, Clemm C, Holler E, Ledderose G, Brehm G, Heim M, Wilmanns W (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76(12):2462–2465CrossRefPubMed
2.
Zurück zum Zitat Jagasia M, Arora M, Flowers MED, Chao NJ, McCarthy PL, Cutler CS, Urbano-Ispizua A, Pavletic SZ, Haagenson MD, Zhang M-J, Antin JH, Bolwell BJ, Bredeson C, Cahn J-Y, Cairo M, Gale RP, Gupta V, Lee SJ, Litzow M, Weisdorf DJ, Horowitz MM, Hahn T (2012) Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119(1):296–307. https://doi.org/10.1182/blood-2011-06-364265CrossRefPubMedPubMedCentral Jagasia M, Arora M, Flowers MED, Chao NJ, McCarthy PL, Cutler CS, Urbano-Ispizua A, Pavletic SZ, Haagenson MD, Zhang M-J, Antin JH, Bolwell BJ, Bredeson C, Cahn J-Y, Cairo M, Gale RP, Gupta V, Lee SJ, Litzow M, Weisdorf DJ, Horowitz MM, Hahn T (2012) Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 119(1):296–307. https://​doi.​org/​10.​1182/​blood-2011-06-364265CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat El-Jawahri A, Li S, Antin JH, Spitzer TR, Armand PA, Koreth J, Nikiforow S, Ballen KK, Ho VT, Alyea EP, Dey BR, McAfee SL, Glotzbecker BE, Soiffer RJ, Cutler CS, Chen Y-B (2016) Improved treatment-related mortality and overall survival of patients with grade IV acute GVHD in the modern years. Biol Blood Marrow Transplant 22(5):910–918. https://doi.org/10.1016/j.bbmt.2015.12.024CrossRefPubMed El-Jawahri A, Li S, Antin JH, Spitzer TR, Armand PA, Koreth J, Nikiforow S, Ballen KK, Ho VT, Alyea EP, Dey BR, McAfee SL, Glotzbecker BE, Soiffer RJ, Cutler CS, Chen Y-B (2016) Improved treatment-related mortality and overall survival of patients with grade IV acute GVHD in the modern years. Biol Blood Marrow Transplant 22(5):910–918. https://​doi.​org/​10.​1016/​j.​bbmt.​2015.​12.​024CrossRefPubMed
6.
Zurück zum Zitat Hahn T, McCarthy PL Jr, Zhang MJ, Wang D, Arora M, Frangoul H, Gale RP, Hale GA, Horan J, Isola L, Maziarz RT, van Rood JJ, Gupta V, Halter J, Reddy V, Tiberghien P, Litzow M, Anasetti C, Pavletic S, Ringdén O (2008) Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol 26(35):5728–5734. https://doi.org/10.1200/jco.2008.17.6545CrossRefPubMedPubMedCentral Hahn T, McCarthy PL Jr, Zhang MJ, Wang D, Arora M, Frangoul H, Gale RP, Hale GA, Horan J, Isola L, Maziarz RT, van Rood JJ, Gupta V, Halter J, Reddy V, Tiberghien P, Litzow M, Anasetti C, Pavletic S, Ringdén O (2008) Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol 26(35):5728–5734. https://​doi.​org/​10.​1200/​jco.​2008.​17.​6545CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Slimings C, Armstrong P, Beckingham WD, Bull AL, Hall L, Kennedy KJ, Marquess J, McCann R, Menzies A, Mitchell BG, Richards MJ, Smollen PC, Tracey L, Wilkinson IJ, Wilson FL, Worth LJ, Riley TV (2014) Increasing incidence of Clostridium difficile infection, Australia, 2011–2012. Med J Aust 200(5):272–276. https://doi.org/10.5694/mja13.11153CrossRefPubMed Slimings C, Armstrong P, Beckingham WD, Bull AL, Hall L, Kennedy KJ, Marquess J, McCann R, Menzies A, Mitchell BG, Richards MJ, Smollen PC, Tracey L, Wilkinson IJ, Wilson FL, Worth LJ, Riley TV (2014) Increasing incidence of Clostridium difficile infection, Australia, 2011–2012. Med J Aust 200(5):272–276. https://​doi.​org/​10.​5694/​mja13.​11153CrossRefPubMed
12.
Zurück zum Zitat Bhutani D, Jaiyeoba C, Kim S, Naylor P, Uberti JP, Ratanatharathorn V, Ayash L, Deol A, Alavi A, Revankar S, Chandrasekar P (2019) Relationship between clostridium difficile infection and gastrointestinal graft versus host disease in recipients of allogeneic stem cell transplantation. Bone Marrow Transplant 54(1):164–167. https://doi.org/10.1038/s41409-018-0270-xCrossRefPubMed Bhutani D, Jaiyeoba C, Kim S, Naylor P, Uberti JP, Ratanatharathorn V, Ayash L, Deol A, Alavi A, Revankar S, Chandrasekar P (2019) Relationship between clostridium difficile infection and gastrointestinal graft versus host disease in recipients of allogeneic stem cell transplantation. Bone Marrow Transplant 54(1):164–167. https://​doi.​org/​10.​1038/​s41409-018-0270-xCrossRefPubMed
14.
Zurück zum Zitat Ramanathan M, Kim S, He N, Chen M, Hematti P, Abid MB, Rotz SJ, Williams KM, Lazarus HM, Wirk B, Yin DE, Kanakry CG, Perales M-A, Chemaly RF, Dandoy CE, Riches M, Ustun C (2023) The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant—a CIBMTR study. Bone Marrow Transplant 58(4):360–366. https://doi.org/10.1038/s41409-022-01896-zCrossRefPubMed Ramanathan M, Kim S, He N, Chen M, Hematti P, Abid MB, Rotz SJ, Williams KM, Lazarus HM, Wirk B, Yin DE, Kanakry CG, Perales M-A, Chemaly RF, Dandoy CE, Riches M, Ustun C (2023) The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant—a CIBMTR study. Bone Marrow Transplant 58(4):360–366. https://​doi.​org/​10.​1038/​s41409-022-01896-zCrossRefPubMed
21.
Zurück zum Zitat Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME (2015) National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The (2014) Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 21(3):389-401.e381. https://doi.org/10.1016/j.bbmt.2014.12.001CrossRef Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME (2015) National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. The (2014) Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 21(3):389-401.e381. https://​doi.​org/​10.​1016/​j.​bbmt.​2014.​12.​001CrossRef
26.
Zurück zum Zitat Rogers WS, Westblade LF, Soave R, Jenkins SG, van Besien K, Singh HK, Walsh TJ, Small CB, Shore T, Crawford CV, Satlin MJ (2020) Impact of a multiplexed polymerase chain reaction panel on identifying diarrheal pathogens in hematopoietic cell transplant recipients. Clin Infect Dis 71(7):1693–1700. https://doi.org/10.1093/cid/ciz1068CrossRefPubMed Rogers WS, Westblade LF, Soave R, Jenkins SG, van Besien K, Singh HK, Walsh TJ, Small CB, Shore T, Crawford CV, Satlin MJ (2020) Impact of a multiplexed polymerase chain reaction panel on identifying diarrheal pathogens in hematopoietic cell transplant recipients. Clin Infect Dis 71(7):1693–1700. https://​doi.​org/​10.​1093/​cid/​ciz1068CrossRefPubMed
29.
34.
Zurück zum Zitat Burgos da Silva M, Ponce DM, Dai A, M. Devlin S, Gomes ALC, Moore G, Slingerland J, Shouval R, Armijo GK, DeWolf S, Fei T, Clurman A, Fontana E, Amoretti LA, Wright RJ, Andrlova H, Miltiadous O, Perales M-A, Taur Y, Peled JU, van den Brink MRM (2022) Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease. Blood 140(22):2385–2397. https://doi.org/10.1182/blood.2021015352CrossRefPubMedPubMedCentral Burgos da Silva M, Ponce DM, Dai A, M. Devlin S, Gomes ALC, Moore G, Slingerland J, Shouval R, Armijo GK, DeWolf S, Fei T, Clurman A, Fontana E, Amoretti LA, Wright RJ, Andrlova H, Miltiadous O, Perales M-A, Taur Y, Peled JU, van den Brink MRM (2022) Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease. Blood 140(22):2385–2397. https://​doi.​org/​10.​1182/​blood.​2021015352CrossRefPubMedPubMedCentral
42.
Zurück zum Zitat Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales M-A, Giralt SA, Pamer EG, van den Brink MRM (2015) Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant 21(8):1373–1383. https://doi.org/10.1016/j.bbmt.2015.04.016CrossRefPubMedPubMedCentral Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, Littmann ER, Ling L, Gobourne AC, Miller LC, Docampo MD, Peled JU, Arpaia N, Cross JR, Peets TK, Lumish MA, Shono Y, Dudakov JA, Poeck H, Hanash AM, Barker JN, Perales M-A, Giralt SA, Pamer EG, van den Brink MRM (2015) Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant 21(8):1373–1383. https://​doi.​org/​10.​1016/​j.​bbmt.​2015.​04.​016CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Bilinski J, Grzesiowski P, Sorensen N, Madry K, Muszynski J, Robak K, Wroblewska M, Dzieciatkowski T, Dulny G, Dwilewicz-Trojaczek J, Wiktor-Jedrzejczak W, Basak GW (2017) Fecal microbiota transplantation in patients with blood disorders inhibits gut colonization with antibiotic-resistant bacteria: results of a prospective, single-center study. Clin Infect Dis 65(3):364–370. https://doi.org/10.1093/cid/cix252CrossRefPubMed Bilinski J, Grzesiowski P, Sorensen N, Madry K, Muszynski J, Robak K, Wroblewska M, Dzieciatkowski T, Dulny G, Dwilewicz-Trojaczek J, Wiktor-Jedrzejczak W, Basak GW (2017) Fecal microbiota transplantation in patients with blood disorders inhibits gut colonization with antibiotic-resistant bacteria: results of a prospective, single-center study. Clin Infect Dis 65(3):364–370. https://​doi.​org/​10.​1093/​cid/​cix252CrossRefPubMed
45.
Zurück zum Zitat Pession A, Zama D, Muratore E, Leardini D, Gori D, Guaraldi F, Prete A, Turroni S, Brigidi P, Masetti R (2021) Fecal microbiota transplantation in allogeneic hematopoietic stem cell transplantation recipients: a systematic review. J Pers Med 11 (2). https://doi.org/10.3390/jpm11020100 Pession A, Zama D, Muratore E, Leardini D, Gori D, Guaraldi F, Prete A, Turroni S, Brigidi P, Masetti R (2021) Fecal microbiota transplantation in allogeneic hematopoietic stem cell transplantation recipients: a systematic review. J Pers Med 11 (2). https://​doi.​org/​10.​3390/​jpm11020100
46.
Zurück zum Zitat van Lier YF, Davids M, Haverkate NJE, de Groot PF, Donker ML, Meijer E, Heubel-Moenen FCJI, Nur E, Zeerleder SS, Nieuwdorp M, Blom B, Hazenberg MD (2020) Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med 12 (556). https://doi.org/10.1126/scitranslmed.aaz8926 van Lier YF, Davids M, Haverkate NJE, de Groot PF, Donker ML, Meijer E, Heubel-Moenen FCJI, Nur E, Zeerleder SS, Nieuwdorp M, Blom B, Hazenberg MD (2020) Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. Sci Transl Med 12 (556). https://​doi.​org/​10.​1126/​scitranslmed.​aaz8926
48.
Zurück zum Zitat Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Högenauer C, Malfertheiner P, Mattila E, Milosavljević T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A (2017) European consensus conference on faecal microbiota transplantation in clinical practice. Gut 66(4):569–580. https://doi.org/10.1136/gutjnl-2016-313017CrossRefPubMed Cammarota G, Ianiro G, Tilg H, Rajilić-Stojanović M, Kump P, Satokari R, Sokol H, Arkkila P, Pintus C, Hart A, Segal J, Aloi M, Masucci L, Molinaro A, Scaldaferri F, Gasbarrini G, Lopez-Sanroman A, Link A, de Groot P, de Vos WM, Högenauer C, Malfertheiner P, Mattila E, Milosavljević T, Nieuwdorp M, Sanguinetti M, Simren M, Gasbarrini A (2017) European consensus conference on faecal microbiota transplantation in clinical practice. Gut 66(4):569–580. https://​doi.​org/​10.​1136/​gutjnl-2016-313017CrossRefPubMed
49.
Zurück zum Zitat Shouval R, Youngster I, Geva M, Eshel A, Danylesko I, Shimoni A, Beider K, Fein JA, Sharon I, Koren O, Nagler A (2018) Repeated courses of orally administered fecal microbiota transplantation for the treatment of steroid resistant and steroid dependent intestinal acute graft vs. host disease: a pilot study (NCT 03214289). Blood 132(1):2121–2121. https://doi.org/10.1182/blood-2018-99-110270CrossRef Shouval R, Youngster I, Geva M, Eshel A, Danylesko I, Shimoni A, Beider K, Fein JA, Sharon I, Koren O, Nagler A (2018) Repeated courses of orally administered fecal microbiota transplantation for the treatment of steroid resistant and steroid dependent intestinal acute graft vs. host disease: a pilot study (NCT 03214289). Blood 132(1):2121–2121. https://​doi.​org/​10.​1182/​blood-2018-99-110270CrossRef
Metadaten
Titel
Non-viral pathogens of infectious diarrhoea post-allogeneic stem cell transplantation are associated with graft-versus-host disease
Publikationsdatum
06.11.2023
Erschienen in
Annals of Hematology / Ausgabe 2/2024
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-023-05526-6

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