Fatal graft-versus-host disease associated with solid-organ transplantation

Edward Agura, Douglas M. Smith, George Netto, Ernesto Molmenti, Robert Collins, Marion Levy, Robert Goldstein, Carlos Fasola, Laura Christensen, Judy Baker, Lori Osowski, Jeff McCormack, Lisa Fichte, D. Brian Dawson, Rana Domiati-Saad, Marvin Stone, Goran Klintmalm

Research output: Contribution to journalArticle

Abstract

Graft versus host disease (GVHD) is an important and under-diagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD in our experience with 1082 liver transplants performed at our institution between 1991and 1998. All but one of the patients died; GVHD accounted for 5% of the deaths occurring during the first year after transplantation. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Early in its course, GVHD was difficult to distinguish from CMV disease, bacterial infection or drug reactions. The diagnosis was usually confirmed by sérologie typing of recipient blood T lymphocytes for donor HLA antigens. A variety of treatments were applied including modulation of immune suppression (both greater and lesser) and hematopoietic cytokines (GCSF, GM-CSF). Most patients died from infections. To identify risk factors for severe GVHD, a retrospective analysis was performed comparing the index cases to the rest of our institutional experience: Closely HLA matched recipients, recipients older than 65 years, and recipients whose donors were more than 40 years younger were at higher risk of developing GVHD. The highest risk (22%) occurred in those patients who had one or fewer HLA A, B mismatches and shared at least one HLA DR antigen with their donor. These data suggest that immunologie "blinding" (by HLA matching) and recipient immunocompelence play important roles. This conclusion is further supported by one of our cases which occurred in a patient with congenital immune deficiency. Conclusions: Liver transplant associated GVHD (LTx-GVHD) is a progressive and seemingly irreversible disease process that, once established, is highly fatal. Future approaches should focus on prevention: These might include treatment of the donor to reduce the number of lymphocytes or reduced immunosuppression of the patient in the early post-transplant period. It may also be important to avoid very close HLA matching when using living related liver donors.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000
Externally publishedYes

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Transplantation (surgical)
Organ Transplantation
Graft vs Host Disease
Grafts
Transplants
Liver
Tissue Donors
Blood Grouping and Crossmatching
Pancytopenia
HLA-A Antigens
HLA-B Antigens
Lymphocyte Count
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
HLA Antigens
Exanthema
Bacterial Infections
Liver Transplantation
T-cells
Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Agura, E., Smith, D. M., Netto, G., Molmenti, E., Collins, R., Levy, M., ... Klintmalm, G. (2000). Fatal graft-versus-host disease associated with solid-organ transplantation. Blood, 96(11 PART II).

Fatal graft-versus-host disease associated with solid-organ transplantation. / Agura, Edward; Smith, Douglas M.; Netto, George; Molmenti, Ernesto; Collins, Robert; Levy, Marion; Goldstein, Robert; Fasola, Carlos; Christensen, Laura; Baker, Judy; Osowski, Lori; McCormack, Jeff; Fichte, Lisa; Brian Dawson, D.; Domiati-Saad, Rana; Stone, Marvin; Klintmalm, Goran.

In: Blood, Vol. 96, No. 11 PART II, 2000.

Research output: Contribution to journalArticle

Agura, E, Smith, DM, Netto, G, Molmenti, E, Collins, R, Levy, M, Goldstein, R, Fasola, C, Christensen, L, Baker, J, Osowski, L, McCormack, J, Fichte, L, Brian Dawson, D, Domiati-Saad, R, Stone, M & Klintmalm, G 2000, 'Fatal graft-versus-host disease associated with solid-organ transplantation', Blood, vol. 96, no. 11 PART II.
Agura E, Smith DM, Netto G, Molmenti E, Collins R, Levy M et al. Fatal graft-versus-host disease associated with solid-organ transplantation. Blood. 2000;96(11 PART II).
Agura, Edward ; Smith, Douglas M. ; Netto, George ; Molmenti, Ernesto ; Collins, Robert ; Levy, Marion ; Goldstein, Robert ; Fasola, Carlos ; Christensen, Laura ; Baker, Judy ; Osowski, Lori ; McCormack, Jeff ; Fichte, Lisa ; Brian Dawson, D. ; Domiati-Saad, Rana ; Stone, Marvin ; Klintmalm, Goran. / Fatal graft-versus-host disease associated with solid-organ transplantation. In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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abstract = "Graft versus host disease (GVHD) is an important and under-diagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD in our experience with 1082 liver transplants performed at our institution between 1991and 1998. All but one of the patients died; GVHD accounted for 5{\%} of the deaths occurring during the first year after transplantation. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Early in its course, GVHD was difficult to distinguish from CMV disease, bacterial infection or drug reactions. The diagnosis was usually confirmed by s{\'e}rologie typing of recipient blood T lymphocytes for donor HLA antigens. A variety of treatments were applied including modulation of immune suppression (both greater and lesser) and hematopoietic cytokines (GCSF, GM-CSF). Most patients died from infections. To identify risk factors for severe GVHD, a retrospective analysis was performed comparing the index cases to the rest of our institutional experience: Closely HLA matched recipients, recipients older than 65 years, and recipients whose donors were more than 40 years younger were at higher risk of developing GVHD. The highest risk (22{\%}) occurred in those patients who had one or fewer HLA A, B mismatches and shared at least one HLA DR antigen with their donor. These data suggest that immunologie {"}blinding{"} (by HLA matching) and recipient immunocompelence play important roles. This conclusion is further supported by one of our cases which occurred in a patient with congenital immune deficiency. Conclusions: Liver transplant associated GVHD (LTx-GVHD) is a progressive and seemingly irreversible disease process that, once established, is highly fatal. Future approaches should focus on prevention: These might include treatment of the donor to reduce the number of lymphocytes or reduced immunosuppression of the patient in the early post-transplant period. It may also be important to avoid very close HLA matching when using living related liver donors.",
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T1 - Fatal graft-versus-host disease associated with solid-organ transplantation

AU - Agura, Edward

AU - Smith, Douglas M.

AU - Netto, George

AU - Molmenti, Ernesto

AU - Collins, Robert

AU - Levy, Marion

AU - Goldstein, Robert

AU - Fasola, Carlos

AU - Christensen, Laura

AU - Baker, Judy

AU - Osowski, Lori

AU - McCormack, Jeff

AU - Fichte, Lisa

AU - Brian Dawson, D.

AU - Domiati-Saad, Rana

AU - Stone, Marvin

AU - Klintmalm, Goran

PY - 2000

Y1 - 2000

N2 - Graft versus host disease (GVHD) is an important and under-diagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD in our experience with 1082 liver transplants performed at our institution between 1991and 1998. All but one of the patients died; GVHD accounted for 5% of the deaths occurring during the first year after transplantation. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Early in its course, GVHD was difficult to distinguish from CMV disease, bacterial infection or drug reactions. The diagnosis was usually confirmed by sérologie typing of recipient blood T lymphocytes for donor HLA antigens. A variety of treatments were applied including modulation of immune suppression (both greater and lesser) and hematopoietic cytokines (GCSF, GM-CSF). Most patients died from infections. To identify risk factors for severe GVHD, a retrospective analysis was performed comparing the index cases to the rest of our institutional experience: Closely HLA matched recipients, recipients older than 65 years, and recipients whose donors were more than 40 years younger were at higher risk of developing GVHD. The highest risk (22%) occurred in those patients who had one or fewer HLA A, B mismatches and shared at least one HLA DR antigen with their donor. These data suggest that immunologie "blinding" (by HLA matching) and recipient immunocompelence play important roles. This conclusion is further supported by one of our cases which occurred in a patient with congenital immune deficiency. Conclusions: Liver transplant associated GVHD (LTx-GVHD) is a progressive and seemingly irreversible disease process that, once established, is highly fatal. Future approaches should focus on prevention: These might include treatment of the donor to reduce the number of lymphocytes or reduced immunosuppression of the patient in the early post-transplant period. It may also be important to avoid very close HLA matching when using living related liver donors.

AB - Graft versus host disease (GVHD) is an important and under-diagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD in our experience with 1082 liver transplants performed at our institution between 1991and 1998. All but one of the patients died; GVHD accounted for 5% of the deaths occurring during the first year after transplantation. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Early in its course, GVHD was difficult to distinguish from CMV disease, bacterial infection or drug reactions. The diagnosis was usually confirmed by sérologie typing of recipient blood T lymphocytes for donor HLA antigens. A variety of treatments were applied including modulation of immune suppression (both greater and lesser) and hematopoietic cytokines (GCSF, GM-CSF). Most patients died from infections. To identify risk factors for severe GVHD, a retrospective analysis was performed comparing the index cases to the rest of our institutional experience: Closely HLA matched recipients, recipients older than 65 years, and recipients whose donors were more than 40 years younger were at higher risk of developing GVHD. The highest risk (22%) occurred in those patients who had one or fewer HLA A, B mismatches and shared at least one HLA DR antigen with their donor. These data suggest that immunologie "blinding" (by HLA matching) and recipient immunocompelence play important roles. This conclusion is further supported by one of our cases which occurred in a patient with congenital immune deficiency. Conclusions: Liver transplant associated GVHD (LTx-GVHD) is a progressive and seemingly irreversible disease process that, once established, is highly fatal. Future approaches should focus on prevention: These might include treatment of the donor to reduce the number of lymphocytes or reduced immunosuppression of the patient in the early post-transplant period. It may also be important to avoid very close HLA matching when using living related liver donors.

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