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Published in: Annals of Hematology 5/2018

01-05-2018 | Original Article

Mesenchymal stem cells transplantation in hematological patients with acute graft-versus-host disease: characteristics and risk factors for infectious complications

Authors: Igor Stoma, Igor Karpov, Svetlana Krivenko, Igor Iskrov, Natalia Milanovich, Alla Koritko, Anatoly Uss

Published in: Annals of Hematology | Issue 5/2018

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Abstract

The role of MSCs in infection prevention and treatment is still discussed in transplant and hematological patients. The spectrum and risk factors for infections after MSCs transplantation in patients with acute GVHD have not been studied before. To determine the risk factors and spectrum of infectious complications in patients received mesenchymal stem cell transplantation as a treatment for acute GVHD. A prospective observational study was performed to evaluate the risk factors and characteristics of infectious complications after MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of MSCs transplantation in patients with acute GVHD after allogeneic HSCT were enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile range 0.87–2.16) mln cells/kg per infusion at 91 days (interquartile range 31–131 days) after HSCT. Data relating to age, gender, date, and type of transplantation, characteristics of MSCs, infectious agents, and antimicrobial therapy and prevention regimens were prospectively collected in all of the enrolled patients. The episode of proven infectious complication was set as a primary outcome. There were totally 68 patients with acute GVHD in the study; among them there were 34 cases of MSCs transplantation performed. Among the registered infectious episodes were viral infections (CMV-associated disease, EBV-associated disease), invasive pulmonary aspergillosis, bacterial bloodstream infections, and pneumonia. MSCs transplantation has shown no statistically significant association with risk of infectious complications in patients with acute GVHD in a performed multivariate analysis. Among the most frequent infections in acute GVHD, we have described CMV, invasive aspergillosis, and bacterial infections (bloodstream infections or pneumonia). Among risk factors for infectious complications in patients with acute GVHD with/without MSCs transplantation are progression of main disease and neutropenia below 500 cells/mm3 (for aspergillosis) and unrelated HSCT in the past history and progression of main disease (for bacterial bloodstream infections and pneumonia).
Literature
1.
go back to reference Baron F et al (2015) Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society. J Hematol Oncol 8:4CrossRefPubMedCentralPubMed Baron F et al (2015) Non-myeloablative allogeneic hematopoietic cell transplantation following fludarabine plus 2 Gy TBI or ATG plus 8 Gy TLI: a phase II randomized study from the Belgian Hematological Society. J Hematol Oncol 8:4CrossRefPubMedCentralPubMed
2.
go back to reference Baron F et al (2015) Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation. J Hematol Oncol 8:107CrossRefPubMedCentralPubMed Baron F et al (2015) Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation. J Hematol Oncol 8:107CrossRefPubMedCentralPubMed
4.
go back to reference Kögler G et al (2005) Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 33(5):573–583CrossRefPubMed Kögler G et al (2005) Cytokine production and hematopoiesis supporting activity of cord blood-derived unrestricted somatic stem cells. Exp Hematol 33(5):573–583CrossRefPubMed
5.
go back to reference Ning H et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 22(3):593–599CrossRefPubMed Ning H et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 22(3):593–599CrossRefPubMed
6.
go back to reference Forslöw U et al (2012) Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation. Eur J Haematol 89(3):220–227CrossRefPubMed Forslöw U et al (2012) Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation. Eur J Haematol 89(3):220–227CrossRefPubMed
7.
go back to reference Zhao K et al (2015) Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 21(1):97–104CrossRefPubMed Zhao K et al (2015) Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 21(1):97–104CrossRefPubMed
9.
go back to reference Remberger M, Ringdén O (2012) Treatment of severe acute graft-versus-host disease with mesenchymal stromal cells: a comparison with non-MSC treated patients. Int J Hematol 96(6):822–824CrossRefPubMed Remberger M, Ringdén O (2012) Treatment of severe acute graft-versus-host disease with mesenchymal stromal cells: a comparison with non-MSC treated patients. Int J Hematol 96(6):822–824CrossRefPubMed
10.
go back to reference Lucchini G et al (2012) Mesenchymal stromal cells do not increase the risk of viral reactivation nor the severity of viral events in recipients of allogeneic stem cell transplantation. Stem Cells Int 2012:690236CrossRefPubMedCentralPubMed Lucchini G et al (2012) Mesenchymal stromal cells do not increase the risk of viral reactivation nor the severity of viral events in recipients of allogeneic stem cell transplantation. Stem Cells Int 2012:690236CrossRefPubMedCentralPubMed
11.
go back to reference Przepiorka D et al (1995) 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 15(6):825–828PubMed Przepiorka D et al (1995) 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 15(6):825–828PubMed
12.
go back to reference von Bonin M et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43(3):245–251CrossRef von Bonin M et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43(3):245–251CrossRef
13.
go back to reference Freifeld AG et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52(4):E56–E93CrossRefPubMed Freifeld AG et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52(4):E56–E93CrossRefPubMed
14.
go back to reference Ljungman P, Griffiths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 34(8):1094–1097CrossRefPubMed Ljungman P, Griffiths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 34(8):1094–1097CrossRefPubMed
15.
go back to reference Styczynski J et al (2009) Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplantation 43(10):757–770CrossRefPubMed Styczynski J et al (2009) Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplantation 43(10):757–770CrossRefPubMed
16.
go back to reference Patterson TF et al (2016) Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 63(4):E1–e60CrossRefPubMedCentralPubMed Patterson TF et al (2016) Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 63(4):E1–e60CrossRefPubMedCentralPubMed
17.
go back to reference Pappas PG et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62(4):E1–50CrossRefPubMed Pappas PG et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 62(4):E1–50CrossRefPubMed
18.
go back to reference Averbuch D et al (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 98(12):1826–1835CrossRefPubMedCentralPubMed Averbuch D et al (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia. Haematologica 98(12):1826–1835CrossRefPubMedCentralPubMed
19.
go back to reference Stoma I et al (2016) Risk factors for mortality in patients with bloodstream infections during the pre-engraftment period after hematopoietic stem cell transplantation. Blood Res 51(2):102–106CrossRefPubMedCentralPubMed Stoma I et al (2016) Risk factors for mortality in patients with bloodstream infections during the pre-engraftment period after hematopoietic stem cell transplantation. Blood Res 51(2):102–106CrossRefPubMedCentralPubMed
21.
go back to reference Karlsson H et al (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood 112(3):532–541CrossRefPubMed Karlsson H et al (2008) Mesenchymal stem cells exert differential effects on alloantigen and virus-specific T-cell responses. Blood 112(3):532–541CrossRefPubMed
22.
go back to reference von Bahr L et al (2012) Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 18(4):557–564CrossRef von Bahr L et al (2012) Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant 18(4):557–564CrossRef
23.
go back to reference Cassatella MA et al (2011) Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells (Dayton, Ohio) 29(6):1001–1011CrossRef Cassatella MA et al (2011) Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils. Stem Cells (Dayton, Ohio) 29(6):1001–1011CrossRef
24.
go back to reference Auletta JJ, Deans RJ, Bartholomew AM (2012) Emerging roles for multipotent, bone marrow-derived stromal cells in host defense. Blood 119(8):1801–1809CrossRefPubMedCentralPubMed Auletta JJ, Deans RJ, Bartholomew AM (2012) Emerging roles for multipotent, bone marrow-derived stromal cells in host defense. Blood 119(8):1801–1809CrossRefPubMedCentralPubMed
25.
go back to reference Meisel R et al (2011) Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 25(4):648–654CrossRefPubMed Meisel R et al (2011) Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase. Leukemia 25(4):648–654CrossRefPubMed
Metadata
Title
Mesenchymal stem cells transplantation in hematological patients with acute graft-versus-host disease: characteristics and risk factors for infectious complications
Authors
Igor Stoma
Igor Karpov
Svetlana Krivenko
Igor Iskrov
Natalia Milanovich
Alla Koritko
Anatoly Uss
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 5/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3250-8

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