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1
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Izzo A, Pellegrino RA, Locci G, Cesaretti M. Acute graft versus host disease after liver transplantation: where do we stand? Minerva Surg 2023; 78:537-544. [PMID: 36883938 DOI: 10.23736/s2724-5691.23.09868-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
Graft-versus-host disease (GVHD) is a rare complication after liver transplantation (LT), with an estimated incidence rate of 0.5% to 2% and a mortality rate as high as 75%. The classical target organs of GVHD include the intestines, liver, and skin. The damage of these organs is not easy to detect for the clinician as there is no widely accepted clinical or laboratory diagnostic tests; as a result, diagnosis and initiation of therapy are often delayed. Moreover, without prospective clinical trials to reference, evidence guiding therapy is limited. This review summarized the current knowledge, the potential applications and the clinical relevance of GVHD after LT, highlighting novel approaches in grading and management of GVHD.
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Affiliation(s)
- Alessandro Izzo
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari, Italy
| | | | - Giorgia Locci
- Department of Pathology, Brotzu Hospital, Cagliari, Italy
| | - Manuela Cesaretti
- Department of HPB and Liver Transplantation, Brotzu Hospital, Cagliari, Italy -
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2
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Voskanyan SE, Korobka VL, Syutkin VE, Monakhov AR, Maltseva AP, Pak ES, Korobka RV, Kolodyazhny EI, Zubenko SI, Voskanyan YV, Kotsiyaev VY. Development of graft-versus-host disease in a liver recipient. Clinical observations and literature review. RUSSIAN JOURNAL OF TRANSPLANTOLOGY AND ARTIFICIAL ORGANS 2023; 25:38-49. [DOI: 10.15825/1995-1191-2023-3-38-49] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Graft-versus-host disease (GvHD) after liver transplantation (LT) occurs in 0.2–0.3% of liver transplant recipients. Each case is characterized by individual peculiarities of the clinical picture. There are no standards or clinical guidelines for the treatment of GvHD in solid organ recipients; mortality remains very high among these patients. We present two clinical cases of verified GvHD that developed early after LT, and we offer a brief review of the current state of the art in the study of this problem.
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Affiliation(s)
| | - V. L. Korobka
- Rostov Regional Clinical Hospital;
Rostov State Medical University
| | - V. E. Syutkin
- Burnazyan State Medical Research Center;
Sklifosovsky Research Institute for Emergency Medicine
| | - A. R. Monakhov
- Shumakov National Medical Research Center of Transplantology and Artificial Organs
| | | | - E. S. Pak
- Rostov Regional Clinical Hospital;
Rostov State Medical University
| | - R. V. Korobka
- Rostov Regional Clinical Hospital;
Rostov State Medical University
| | | | - S. I. Zubenko
- Shumakov National Medical Research Center of Transplantology and Artificial Organs
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3
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Cooper JP, Abkowitz JL. How I diagnose and treat acute graft-versus-host disease after solid organ transplantation. Blood 2023; 141:1136-1146. [PMID: 36395067 DOI: 10.1182/blood.2022015954] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 11/18/2022] Open
Abstract
Acute graft-versus-host disease (GVHD) is a rare complication after solid organ transplantation (SOT) that carries high mortality. Caused by immunocompetent donor leukocytes within the transplanted organ, which become activated against recipient tissues, GVHD typically develops 2 to 12 weeks after SOT and can affect the skin, gastrointestinal tract, liver, and bone marrow. Signs and symptoms are nonspecific and include a rash, nausea, appetite loss, diarrhea, and cytopenias. Pancytopenia from marrow-directed GVHD is the primary driver of mortality. The diagnosis of GVHD is often delayed but should be confirmed by biopsy of an affected organ. Evidence of donor chimerism in blood or marrow supports the diagnosis. When GVHD is diagnosed we initiate treatment with systemic corticosteroids. At that time, if GVHD only involves skin or oral mucosa we also decrease maintenance immunosuppression levels to allow the recipient to reject the donor immune cells. For GVHD involving the marrow we initiate an allogeneic hematopoietic cell donor search early. In this article, we describe 3 cases of GVHD after SOT, outline our approach to diagnosis and management, and then provide analysis of the 3 instructive cases.
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Affiliation(s)
- Jason P Cooper
- Division of Hematology, Department of Medicine, University of Washington, Seattle, WA
| | - Janis L Abkowitz
- Division of Hematology, Department of Medicine, University of Washington, Seattle, WA
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4
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Hung YT, Chang YR, Wang HN, Lee WC, Lee CF, Chen CB. Diagnostic and therapeutic dilemma in Stevens–Johnson syndrome-like acute graft-versus-host disease after liver transplantation: A case report. Front Immunol 2022; 13:917782. [PMID: 36059444 PMCID: PMC9433559 DOI: 10.3389/fimmu.2022.917782] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 07/27/2022] [Indexed: 11/21/2022] Open
Abstract
Background Acute graft-versus-host disease (aGVHD) is a severe and fatal complication after orthotopic liver transplantation (OLT). Clinical manifestations of severe aGVHD can resemble drug-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and there are also various medications, such as antibiotics and immunosuppressants, used after transplantation, causing a diagnostic dilemma. Furthermore, there have been no standardized diagnostic and therapeutic strategies for OLT-aGVHD due to its rarity. Case summary A 52-year-old man presented with generalized maculopapular eruptions, fever, and pancytopenia 1 month after OLT and 4 days after taking sulfamethoxazole/trimethoprim. After assessment of the scoring criteria for drug causality of drug allergy, histopathological findings of skin biopsy, lymphocyte activation test of the potential offending drug, and microchimerism study, the diagnosis was in favor of aGVHD mimicking SJS/TEN. Considering severe sepsis, the anti-tumor necrosis factor alpha (TNF-α) agent, etanercept, was used to replace tacrolimus and corticosteroid. Skin lesions resolved gradually after anti-TNF-α biologics rescue; tacrolimus and corticosteroid therapy were re-administrated after controlling sepsis. Pancytopenia recovered and the patient was discharged in a stable condition. Conclusion We demonstrated a diagnostic strategy for OLT-aGVHD. Targeting therapy with anti-TNF-α blockade and a temporary withdrawal of traditional immunosuppressants may be among effective and safe therapeutic options of OLT-aGVHD for those with severe sepsis.
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Affiliation(s)
- Yi-Teng Hung
- Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Yau-Ren Chang
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Hsuan-Ning Wang
- Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Dermatology, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan
| | - Wei-Chen Lee
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Chen-Fang Lee
- Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
- Department of Liver and Transplantation Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
- *Correspondence: Chen-Fang Lee, ; Chun-Bing Chen,
| | - Chun-Bing Chen
- Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taiwan
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan City, Taiwan
- Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
- Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan
- Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan
- School of Medicine, National Tsing Hua University, Hsinchu, Taiwan
- *Correspondence: Chen-Fang Lee, ; Chun-Bing Chen,
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5
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Chen Z, Han C, Wang X, He Y, Liang T, Mo S, Li X, Zhu G, Su H, Ye X, Lv Z, Shang L, Wen Z, Peng M, Peng T. Graft versus host disease after liver transplantation following radiotherapy for the treatment of hepatocellular carcinoma: A case report and literature review. SAGE Open Med Case Rep 2022; 10:2050313X221101747. [PMID: 35646373 PMCID: PMC9136437 DOI: 10.1177/2050313x221101747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 04/27/2022] [Indexed: 11/16/2022] Open
Abstract
Graft versus host disease after solid organ transplantation is very rare. This article reports a case of graft versus host disease after liver transplantation following targeted therapy and radiotherapy for the treatment of hepatocellular carcinoma. The patient developed a symptomatic skin rash and pancytopenia 13 days after surgery, which was confirmed as graft versus host disease after liver transplantation by histopathology and fluorescence in situ hybridization. Early diagnosis of graft versus host disease after solid organ transplantation is difficult and often delayed due to nonspecific manifestations that overlap with other diseases. Currently, the treatment of graft versus host disease after liver transplantation occurs by either strengthening the immune suppression or weakening the immune suppression; however, there is no unified standard treatment strategy. We found that in addition to age, gender, and human leukocyte antigen type, preoperative radiotherapy is a likely risk factor for graft versus host disease after liver transplantation.
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Affiliation(s)
- Zijun Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiangkun Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yongfei He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Tianyi Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Shutian Mo
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xuan Li
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xinping Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zili Lv
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Liming Shang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhang Wen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Minhao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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6
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Newell LF, Dunlap J, Gatter K, Bagby GC, Press RD, Cook RJ, Fletcher L, Leonard JT, Leong KM, Bubalo JS, Olyaei A, Deloughery TG, Maziarz RT, Maynard E, Orloff SL, Enestvedt CK. Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations. Am J Transplant 2021; 21:3894-3906. [PMID: 33961341 DOI: 10.1111/ajt.16635] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 04/16/2021] [Accepted: 04/30/2021] [Indexed: 01/25/2023]
Abstract
Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.
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Affiliation(s)
- Laura F Newell
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Jennifer Dunlap
- Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA
| | - Ken Gatter
- Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA
| | - Grover C Bagby
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Richard D Press
- Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA
| | - Rachel J Cook
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Luke Fletcher
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Jessica T Leonard
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Kelli M Leong
- Department of Pharmacy, Oregon Health & Science University, Portland, Oregon, USA
| | - Joseph S Bubalo
- Department of Pharmacy, Oregon Health & Science University, Portland, Oregon, USA
| | - Ali Olyaei
- Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, Oregon, USA
| | - Thomas G Deloughery
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Richard T Maziarz
- Knight Cancer Institute, Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Erin Maynard
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - Susan L Orloff
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
| | - C Kristian Enestvedt
- Department of Surgery, Division of Abdominal Organ Transplantation, Oregon Health & Science University, Portland, Oregon, USA
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7
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Moosavi MM, Duncan A, Stowell SR, Roback JD, Sullivan HC. Passenger Lymphocyte Syndrome; a Review of the Diagnosis, Treatment, and Proposed Detection Protocol. Transfus Med Rev 2020; 34:178-187. [PMID: 32826130 DOI: 10.1016/j.tmrv.2020.06.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 12/14/2022]
Abstract
Passenger lymphocyte syndrome (PLS) is caused by the transfer of B-lymphocytes present in the donor graft into the recipient circulation following solid organ or hematopoietic stem cell transplantation. These cells may produce antibodies against the recipient's red blood cells, thereby triggering antibody dependent cytotoxicity and erythroid clearance, with potential resulting hemolysis and jaundice. Although uncommon, the true incidence is unknown because many cases are subclinical, with only serologic findings or with non significant levels of hemolysis detectable clinically or by laboratory monitoring. Thus, these cases may not be detected in the immediate perioperative period. No standardized consensus exists on screening for PLS in patients. Through a review of the literature from 2009 to 2019, we aim to approximate the incidence of this condition in different solid organ transplant settings, as well as to streamline recognition, detection, and management of PLS early in the disease course to prevent adverse outcomes and minimize invasive therapy. The resultant literature review yielded 22 case reports and 8 case series comprising 71 solid organ transplant patients. Hematopoietic stem cell transplant cases were excluded, as PLS cases related to solid organ transplant were the primary focus of this review. Our institution has traditionally handled PLS on a case-by-case basis, although we hope to improve this process through an introduction of an algorithm based on review of the literature and formalized communication with primary caregivers.
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Affiliation(s)
- Mitchell M Moosavi
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Alexander Duncan
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Sean R Stowell
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - John D Roback
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA
| | - Harold Clifford Sullivan
- Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.
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8
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Wood A, Eghtesad B, Lindenmeyer CC. Graft-Versus-Host Disease After Liver Transplantation. Clin Liver Dis (Hoboken) 2020; 15:81-84. [PMID: 32226622 PMCID: PMC7098667 DOI: 10.1002/cld.884] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 09/17/2019] [Indexed: 02/04/2023] Open
Abstract
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-wood a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-interview-lindenmeyer an interview with the author.
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Affiliation(s)
- Ashley Wood
- Department of Internal MedicineCleveland ClinicClevelandOH
| | - Bijan Eghtesad
- Department of General Surgery, Digestive Disease and Surgery InstituteCleveland ClinicClevelandOH
| | - Christina C. Lindenmeyer
- Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease and Surgery InstituteCleveland ClinicClevelandOH
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9
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Current status of graft-versus-host disease after intestinal transplantation. Curr Opin Organ Transplant 2019; 24:199-206. [DOI: 10.1097/mot.0000000000000624] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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10
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Minnee RC, Fieuws S, Jochmans I, Aerts R, Sainz Barriga M, Debaveye Y, Maertens J, Vandenberghe P, Laleman W, van der Merwe S, Verslype C, Cassiman D, Ferdinande P, Nevens F, Pirenne J, Monbaliu D. Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review. Am J Transplant 2018; 18:3007-3020. [PMID: 29734503 DOI: 10.1111/ajt.14923] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 04/25/2018] [Accepted: 04/26/2018] [Indexed: 01/25/2023]
Abstract
Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.
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Affiliation(s)
- R C Minnee
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - S Fieuws
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, KU Leuven-University of Leuven, Leuven, Belgium.,University Hasselt, Hasselt, Belgium
| | - I Jochmans
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - R Aerts
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - M Sainz Barriga
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - Y Debaveye
- Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - J Maertens
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium
| | - P Vandenberghe
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium.,Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
| | - W Laleman
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - S van der Merwe
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - C Verslype
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - D Cassiman
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - P Ferdinande
- Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - F Nevens
- Department of Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - J Pirenne
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
| | - D Monbaliu
- Abdominal transplant surgery and transplantation coordination, University Hospitals Leuven, Leuven, Belgium.,Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium
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11
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Pahari H, Nagai S, Skorupski S, Salgia R. Graft-versus-host disease of the central nervous system after liver transplantation: A rare complication. Am J Transplant 2018; 18:2591-2594. [PMID: 29935052 DOI: 10.1111/ajt.14981] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/04/2018] [Accepted: 06/12/2018] [Indexed: 01/25/2023]
Abstract
Graft-versus-host disease (GVHD) of the central nervous system (CNS) following solid organ transplantation is a rare but serious complication and has been previously reported after bone marrow transplantation. GVHD after liver transplantation is a rare entity with a high mortality rate. We report the case of a patient who developed GVHD and subsequently had seizures and altered mental status after deceased donor liver transplantation. The diagnosis of GVHD of the CNS was established by short tandem repeat loci analysis of the cerebrospinal fluid using the polymerase chain reaction technique and gene mapping software. To our knowledge, this is the first reported case of CNS-GVHD following liver transplantation. He eventually died of sepsis and multiorgan failure, in keeping with the overall poor prognosis of CNS-GVHD.
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Affiliation(s)
- Hirak Pahari
- Division of Transplant Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Shunji Nagai
- Division of Transplant Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Sharon Skorupski
- Transplant Immunology Laboratory, Henry Ford Hospital, Detroit, MI, USA
| | - Reena Salgia
- Division of Gastroenterology and Hepatology, Henry Ford Hospital, Detroit, MI, USA
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12
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Sharkey LM, Peacock S, Russell NK, Middleton SJ, Butler AJ. Graft versus host disease after multivisceral transplantation: A UK center experience and update on management. Clin Transplant 2018. [PMID: 29543344 DOI: 10.1111/ctr.13239] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Lisa M. Sharkey
- Department of Gastroenterology; Cambridge University Hospitals NHS Foundation Trust; Cambridge UK
| | - Sarah Peacock
- Tissue Typing Laboratory; Cambridge University Hospitals NHS Foundation Trust; Cambridge UK
| | - Neil K. Russell
- Department of Transplant Surgery; Cambridge University Hospitals NHS Foundation Trust; Cambridge UK
| | - Stephen J. Middleton
- Department of Gastroenterology; Cambridge University Hospitals NHS Foundation Trust; Cambridge UK
| | - Andrew J. Butler
- Department of Transplant Surgery; Cambridge University Hospitals NHS Foundation Trust; Cambridge UK
- Department of Surgery and the NIHR Cambridge Biomedical Research Centre; University of Cambridge; Addenbrooke's Hospital; Cambridge UK
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13
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14
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Rashidi A, Brennan DC, Amarillo IE, Wellen JR, Cashen A. Mixed Donor Chimerism Following Simultaneous Pancreas-Kidney Transplant. EXP CLIN TRANSPLANT 2017; 16:307-313. [PMID: 28661312 DOI: 10.6002/ect.2016.0299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Graft-versus-host disease after solid-organ transplant is exceedingly rare. Although the precise pathogenetic mechanisms are unknown, a progressive increase in donor chimerism is a requirement for its development. The incidence of mixed donor chimerism and its timeline after simultaneous pancreas-kidney transplant is unknown. MATERIALS AND METHODS After encountering 2 cases of graft-versus-host disease after simultaneous pancreas-kidney transplant at our institution over a period of < 2 years, a collaborative pilot study was conducted by the bone marrow transplant, nephrology, and abdominal transplant surgery teams. We enrolled all consecutive patients undergoing sex-mismatched simultaneous pancreas-kidney transplant over 1 year and longitudinally monitored donor chimerism using fluorescence in situ hybridization for sex chromosomes. RESULTS We found no evidence for chimerism in our 7 patients. In a comprehensive literature review, we found a total of 25 previously reported cases of graft-versus-host disease after kidney, pancreas, and simultaneous pancreas-kidney transplants. The median onset of graft-versus-host disease was approximately 5 weeks after transplant, with a median of about 2 weeks of delay between first presentation and diagnosis. Skin, gut, and bone marrow were almost equally affected at initial presentation, and fever of unknown origin occurred in more than half of patients. The median survival measured from the first manifestation of graft-versus-host disease was only 48 days. CONCLUSIONS Within the limitations related to small sample size, our results argue against an unusually high risk of graft-versus-host disease after simultaneous pancreas-kidney transplant. Collaboration between solid-organ and stem cell transplant investigators can be fruitful and can improve our understanding of the complications that are shared between the 2 fields.
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Affiliation(s)
- Armin Rashidi
- U.O.C. Division of Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology, Azienda Ospedaliera Universitaria, Second University of Naples, Naples, Italy
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15
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Graft Versus Host Disease After Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management. Transplantation 2017; 100:2661-2670. [PMID: 27495762 DOI: 10.1097/tp.0000000000001406] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature. METHODS Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed. RESULTS One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-α antagonists. CONCLUSIONS Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-α antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.
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16
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Rashidi A. A mathematical model provides new insights into solid organ transplant-associated acute graft-versus-host disease. Clin Transplant 2016; 30:1173-7. [PMID: 27465565 DOI: 10.1111/ctr.12797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2016] [Indexed: 11/29/2022]
Abstract
Solid organ transplantation-associated acute graft-versus-host disease (SOT-aGvHD) is a rare but highly fatal condition. Our poor understanding of this entity in addition to its rarity has hampered treatment progress and most patients succumb to the disease. A mechanistic mathematical model is developed to replicate and explain the complex pathogenesis of SOT-aGvHD. The model captures a number of important features of SOT-aGvHD including (i) the occurrence of stable and persistent mixed chimerism in some, but not all, cases, (ii) fluctuation in chimerism in some persistently mixed chimeric cases, (iii) rare occurrence of full donor chimerism, and (iv) beneficial effect of escalating immunosuppression in some cases of SOT-aGvHD and detrimental effect in others. In addition, the model predicts the conditions under which escalation or de-escalation of immunosuppression would be the preferred treatment strategy. In an exceedingly rare condition such as SOT-aGvHD, where prospective trials are not feasible, mathematical modeling can provide useful insights into pathogenesis and treatment.
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Affiliation(s)
- Armin Rashidi
- Bone Marrow Transplantation and Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
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17
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A rare but life-threatening complication in liver transplant recipients. GASTROENTEROLOGY REVIEW 2016; 11:62-4. [PMID: 27110316 PMCID: PMC4814535 DOI: 10.5114/pg.2015.52562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 02/11/2015] [Indexed: 11/17/2022]
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18
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Rai V, Dietz NE, Agrawal DK. Immunological basis for treatment of graft versus host disease after liver transplant. Expert Rev Clin Immunol 2016; 12:583-93. [PMID: 26795873 DOI: 10.1586/1744666x.2016.1145056] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Graft versus host disease (GVHD) after liver transplant, although a rare disease, has a very high mortality rate. GVHD occurs due to immunoreactions caused by donor T lymphocytes and host cell surface antigens resulting in proliferation and clonal expansion of T lymphocyte. Migration of effector cells, including macrophages, NK cells and cytotoxic T lymphocyte, to the target organs such as skin, intestine and bone marrow results in skin rashes, diarrhea and bone marrow depression. GVHD is diagnosed by clinical symptoms, histopathological findings and by the presence of chimerism. The delayed diagnosis, opportunistic infections and lack of definitive treatment of post orthotopic liver transplant (OLT)-GVHD results in sepsis and multi-organ failure leading to very low survival rates. In this review, we have focused on early diagnosis and critically discuss novel treatment modalities to decrease the incidence of GVHD.
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Affiliation(s)
- Vikrant Rai
- a Department of Clinical and Translational Science , Creighton University School of Medicine , Omaha , NE , USA
| | - Nicholas Edward Dietz
- b Department of Pathology , Creighton University School of Medicine , Omaha , NE , USA
| | - Devendra K Agrawal
- a Department of Clinical and Translational Science , Creighton University School of Medicine , Omaha , NE , USA
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19
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Houston BL, Yan M, Tinckam K, Kamel-Reid S, Chang H, Kuo KHM, Tsien C, Seftel MD, Avitzur Y, Grant D, Cserti-Gazdewich CM. Extracorporeal photopheresis in solid organ transplant-associated acute graft-versus-host disease. Transfusion 2016; 56:962-9. [PMID: 26892365 DOI: 10.1111/trf.13467] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 10/18/2015] [Accepted: 10/19/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Extracorporeal photopheresis (ECP) culls pathogenic T lymphocytes, be these the clones of cutaneous T-cell lymphoma, or mediators of chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT-GVHD). Whether or not ECP may have an effect in the rarer instances of solid organ transplantation-associated GVHD (SOT-GVHD) is unclear. Mortality rates in SOT-GVHD rival those of transfusion-associated GVHD, with fatalities preceded by pancytopenia and peripheral blood chimerism (PBC) levels exceeding 20%. ECP has been described in two SOT-GVHD cases to date, with one surviving. STUDY DESIGN AND METHODS Clinicolaboratory features (including HLA relationships) in a case of multivisceral transplantation were reviewed from the time of surgery to the onset and progression of SOT-GVHD. ECP, which was introduced as a less immunosuppressive and more selective intervention, was assessed for its effect on serial PBC (as measured by short-tandem-repeat analysis) and clinical outcome. RESULTS Multivisceral SOT-GVHD manifested with erythroderma, neutropenic sepsis, and PBC increasing from 6% on Posttransplant Day (PTD) 38 to 78% by PTD 60 (at a doubling time of 6 days despite corticosteroids). ECP was administered on PTDs 62 and 67 and was associated with the first evidence of PBC decay to 67% on PTD 69. Death nevertheless ensued on the last day of salvage antithymocyte globulin (PTDs 69-73) despite further PBC reduction to 41%. CONCLUSION Further study is needed to determine if the sooner or more frequent application of ECP might attenuate the high case fatality rates of SOT-GVHD.
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Affiliation(s)
| | - Matthew Yan
- Department of Medical Oncology and Hematology, University of Toronto
| | - Kathryn Tinckam
- Department of Medicine.,Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario
| | - Suzanne Kamel-Reid
- Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario
| | - Hong Chang
- Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario
| | - Kevin H M Kuo
- Department of Medicine.,Department of Medical Oncology and Hematology, University of Toronto
| | | | - Matthew D Seftel
- Department of Medical Oncology and Hematology, CancerCare Manitoba, and Section of Hematology/Oncology, Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba
| | - Yaron Avitzur
- Department of Paediatrics, Hospital for Sick Children, Toronto
| | - David Grant
- Department of Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Christine M Cserti-Gazdewich
- Department of Medicine.,Department of Medical Oncology and Hematology, University of Toronto.,Laboratory Medicine Program, University Health Network and University of Toronto, Toronto, Ontario
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20
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Schulman JM, Yoon C, Schwarz J, Vagefi PA, Mully TW, Shinkai K. Absence of peripheral blood chimerism in graft-vs-host disease following orthotopic liver transplantation: case report and review of the literature. Int J Dermatol 2013; 53:e492-8. [PMID: 24372059 DOI: 10.1111/ijd.12149] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Graft-vs-host disease (GVHD) is a rare and often fatal complication of orthotopic liver transplantation (OLT). The skin is frequently involved early in disease progression, but clinical and histopathological features may be nonspecific, presenting a diagnostic challenge. While the detection of peripheral blood chimerism has been proposed as a diagnostic criterion for post-OLT GVHD, it is not known whether peripheral blood chimerism is an absolute requirement for the diagnosis. MATERIALS AND METHODS We report a case of a 57-year-old man who developed post-OLT GVHD with cutaneous, enteric, and bone marrow involvement. We also review the epidemiology, pathogenesis, clinical presentation, histopathology, molecular diagnostic techniques, and treatment of GVHD following liver transplantation. RESULTS In our patient, analysis of the peripheral blood by short-tandem repeat polymerase chain reaction did not detect circulating donor lymphocytes. Donor lymphocytes were detected in the buccal mucosa, however, confirming the diagnosis. A review of chimerism patterns in 63 previously published cases of post-OLT GVHD reveals that this is the first reported case in which chimerism was absent in the peripheral blood but present in another site. CONCLUSIONS Peripheral blood chimerism may be absent in cases of post-OLT GVHD. A combination of clinical, histopathological, and molecular features is therefore required to make this challenging diagnosis.
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Affiliation(s)
- Joshua M Schulman
- Department of Dermatology, University of California, San Francisco, CA, USA
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21
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Uchiyama H, Kayashima H, Matono R, Shirabe K, Yoshizumi T, Ikegami T, Soejima Y, Matsuura T, Taguchi T, Maehara Y. Relevance of HLA compatibility in living donor liver transplantation: the double-edged sword associated with the patient outcome. Clin Transplant 2013; 26:E522-9. [PMID: 23061761 DOI: 10.1111/ctr.12019] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
HLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA-A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host-versus-graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft-versus-host disease (GVHD) was also analyzed. No recipients with recipient-against-donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with "R→D MM 0" together with "donor-against-recipient MM 3" died of fatal GVHD. HLA compatibility in LDLT not only affected the long-term acceptance of graft livers but also the risk of fatal GVHD.
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Affiliation(s)
- Hideaki Uchiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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22
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Yildiz BD. Where are we at with short bowel syndrome and small bowel transplant. World J Transplant 2012; 2:95-103. [PMID: 24175201 PMCID: PMC3782239 DOI: 10.5500/wjt.v2.i6.95] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Revised: 06/26/2012] [Accepted: 10/31/2012] [Indexed: 02/05/2023] Open
Abstract
Intestinal failure can be defined as the critical reduction of functional gut mass below the minimal amount necessary for adequate digestion and absorption to satisfy body nutrient and fluid requirements in adults or children. Short bowel syndrome (SBS) is characterized by a state of malabsorption following extensive resection of the small bowel. SBS may occur after resection of more than 50% and is certain after resection of more than 70% of the small intestine, or if less than 100 cm of small bowel is left. Several treatment modalities other than total parenteral nutrition, including hormones (recombinant human growth hormone, glucagon-like peptide-2) and tailoring surgeries (Bianchi procedure, serial transverse enteroplasty), had been proposed, however these were either experimental or inefficient. Small bowel transplant is a rather new approach for SBS. The once feared field of solid organ transplantation is nowadays becoming more and more popular, even in developing countries. This is partially secondary to the developments in immunosuppressive strategy. In this regard, alemtuzumab deserves special attention. There are more complex surgeries, such as multivisceral transplantation, for multi-organ involvement including small bowel. This latter technique is relatively new when compared to small bowel transplant, and is performed in certain centers worldwide. In this review, an attempt is made to give an insight into small bowel syndrome, small bowel transplantation, and related issues.
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Affiliation(s)
- Baris Dogu Yildiz
- Baris Dogu Yildiz, Transplantation Surgery, Ankara Numune Teaching and Research Hospital, Ankara 06100, Turkey
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23
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Akbulut S, Yilmaz M, Yilmaz S. Graft-versus-host disease after liver transplantation: A comprehensive literature review. World J Gastroenterol 2012; 18:5240-8. [PMID: 23066319 PMCID: PMC3468857 DOI: 10.3748/wjg.v18.i37.5240] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2012] [Revised: 06/11/2012] [Accepted: 06/28/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the factors affecting mortality in patients who developed graft-versus-host disease (GvHD) after liver transplantation (LT).
METHODS: We performed a review of studies of GvHD following LT published in the English literature and accessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phrases, 88 articles were identified. Of these, 61 articles containing most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association (P < 0.05) were then subjected to multivariate analyses using a Cox proportional-hazards model.
RESULTS: The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years (range: 8 mo to 74 years), who met the inclusion criteria for the present study. Deaths occurred in 59 (67.8%) patients, whereas 28 (32.2%) survived after a mean follow-up period of 280.8 ± 316.2 d (range: 27-2285 d). Among the most frequent symptoms were rash (94.2%), fever (66.6%), diarrhea (54%), and pancytopenia (54%). The average time period between LT and first symptom onset was 60.6 ± 190.1 d (range: 2-1865 d). The Kaplan-Meier analysis revealed that pancytopenia (42.8% vs 59.3%, P = 0.03), diarrhea (39.2% vs 61.0%, P = 0.04), age difference between the recipient and the donor (14.6 ± 3.1 years vs 22.6 ± 2.7 years, P < 0.0001), and time from first symptom occurrence to diagnosis or treatment (13.3 ± 2.6 mo vs 15.0 ± 2.3 mo, P < 0.0001) were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, determined that an age difference between the recipient and donor was an independent risk factor (P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7).
CONCLUSION: This study showed that an age difference between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.
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24
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Rogulj IM, Deeg J, Lee SJ. Acute graft versus host disease after orthotopic liver transplantation. J Hematol Oncol 2012; 5:50. [PMID: 22889203 PMCID: PMC3445845 DOI: 10.1186/1756-8722-5-50] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Accepted: 07/27/2012] [Indexed: 11/25/2022] Open
Abstract
Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1–2%, but an 80–100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.
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Affiliation(s)
- Inga Mandac Rogulj
- University of Zagreb School of Medicine, University Hospital Merkur, Zagreb, Croatia
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25
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Yilmaz M, Ozdemir F, Akbulut S, Ersan V, Koc C, Koc S, Yilmaz S. Chronic graft-versus-host disease after liver transplantation: a case report. Transplant Proc 2012; 44:1751-1753. [PMID: 22841262 DOI: 10.1016/j.transproceed.2012.05.036] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a rare but significant complication, occurring in 1%-2% of cases with a mortality rate of 85%- 90%. It occurs when donor passenger lymphocytes mount an alloreactive response against the host's histocompatibility antigens. It presents as fever, rash, and diarrhea with or without pancytopenia. Between March 2002 and September 2011, among 656 OLT patients 1 (0.15%) had acute GVHD. A biopsy at the 7th posttransplantation month revealed chronic GVHD. Consequently, in the cases that had fever, rash, and/or desquamation of the any part of body after liver transplantation, GVHD must be considered and skin biopsies must be planned for the diagnosis.
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Affiliation(s)
- M Yilmaz
- Department of Surgery, Division of Liver Traansplantation, Inonu University Faculty of Medicine, Malatya, Turkey.
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26
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Chen XB, Yang J, Xu MQ, Wen TF, Yan LN. Unsuccessful treatment of four patients with acute graft- vs-host disease after liver transplantation. World J Gastroenterol 2012; 18:84-9. [PMID: 22228975 PMCID: PMC3251810 DOI: 10.3748/wjg.v18.i1.84] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 06/23/2011] [Accepted: 06/30/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation.
METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed.
RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.
CONCLUSION: New and effective treatments are required for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.
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27
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Graft-versus-host disease after intestinal and multivisceral transplantation. Transplantation 2011; 91:219-24. [PMID: 21076376 DOI: 10.1097/tp.0b013e3181ff86ec] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Graft-versus-host-disease (GVHD) is a rare complication but carries a high mortality after transplantation. We retrospectively evaluated the incidence, risk factors and impact of this complication on the survival outcome of intestinal transplantation at a single center. METHODS 241 patients who underwent intestinal transplantation between March 1994 and July 2007 were analyzed for evidence of GVHD. A diagnosis of GVHD was based on clinical presentations and confirmed by histological findings. RESULTS Of the 241 patients, 22 (9.1%) were diagnosed as GVHD. The median time of GVHD onset was 75 days (range, 14-1,408). The incidence of GVHD was significantly higher in young children than in adults (13.2 versus 4.4%, P = 0.05). The multivisceral graft recipients were more likely to develop GVHD compared with those of isolated small bowel (12.4% versus 4.6%, P = 0.05). The presence of recipient splenectomy was significantly associated with the incidence of GVHD (P = 0.03). The inclusion of the spleen in the multivisceral grafts tended to be at an increased risk of GVHD compared with the group without the spleen transplant (12.3% versus 7.9%, P = 0.43). A total of 16 patients with GVHD died during the entire follow-up. Infection was the leading cause of death in 55% patients. CONCLUSIONS GVHD is a fatal and progressive complication of small bowel transplantation. Younger children, multivisceral graft recipients, and particularly those with splenectomy are at high risk of developing GVHD after transplantation.
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28
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Zhang Y, Ruiz P. Solid organ transplant-associated acute graft-versus-host disease. Arch Pathol Lab Med 2010; 134:1220-4. [PMID: 20670147 DOI: 10.5858/2008-0679-rs.1] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Solid organ transplant-associated graft-versus-host disease is an infrequent and potentially lethal complication. The incidence of this complication varies according to the type of organ transplant with higher rates associated with liver and small bowel transplants. The clinical presentation typically includes fever and skin rash, and most cases quickly advance to become a multisystem disease affecting the bone marrow and other nontransplanted solid organs. The diagnosis is based on the clinical symptoms, pathologic changes in biopsied tissues, and systemic lymphoid chimerism. The mortality of this disease can exceed 75% after liver transplant and most patients die from infections or hemorrhage due to bone marrow failure. There is no standard treatment strategy for this complication, and the management mainly consists of both prophylaxis and immediate treatment without delay. This short review summarizes the current pathogenesis, diagnosis, and treatment of this entity.
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Affiliation(s)
- Yaxia Zhang
- Department of Pathology, University of Miami-Jackson Memorial Hospital and Sylvester Comprehensive Cancer Center, Miami, Florida, USA
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29
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Thin L, Macquillan G, Adams L, Garas G, Seow C, Cannell P, Augustson B, Mitchell A, Delriveire L, Jeffrey G. Acute graft-versus-host disease after liver transplant: novel use of etanercept and the role of tumor necrosis factor alpha inhibitors. Liver Transpl 2009; 15:421-6. [PMID: 19326415 DOI: 10.1002/lt.21704] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Acute graft-versus-host disease following orthotopic liver transplantation is a rare but feared complication arising in 1% to 2% of cases with a dismal prognosis. It most often presents as fever, rash, and diarrhea with or without pancytopenia. Patients die from complications of marrow failure such as sepsis or bleeding. Because of its low incidence, there is no clear treatment protocol for this complication. Both increasing and withdrawing immunosuppression have been attempted with variable success. Although anti-tumor necrosis factor alpha therapy has been widely used for the treatment of steroid-resistant acute graft-versus-host disease in the hematopoietic stem cell transplant setting, there previously have been no reported cases of its use in liver transplantation. The aim of this report is to review a case of acute graft-versus-host disease and the use of etanercept to manage this complication. Etanercept has never previously been used in liver transplantation complicated by acute graft-versus-host disease. In the hematology literature, the success of its use is offset by significant rates of serious infectious (especially fungal) complications. However, preliminary results are encouraging and offer insight into its use as a potentially viable therapeutic option. We report the first successful use of etanercept in liver transplantation-associated graft-versus-host disease, albeit complicated by invasive aspergillosis, and recommend concurrent antifungal prophylaxis when the drug is used in this setting.
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Affiliation(s)
- Lena Thin
- West Australian Liver Transplant Service, Perth, Western Australia, Australia.
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30
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Cserti-Gazdewich CM, Waddell TK, Singer LG, Chaparro C, Pendergrast JM, Hawes J, denHollander N, Tinckam K, Keshavjee S. Passenger Lymphocyte Syndrome With or Without Immune Hemolytic Anemia in all Rh-Positive Recipients of Lungs From Rhesus Alloimmunized Donors: Three New Cases and a Review of the Literature. Transfus Med Rev 2009; 23:134-45. [DOI: 10.1016/j.tmrv.2008.12.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Pavenski K, Kamel-Reid S, Wei C, Cserti-Gazdewich CM. Lung transplantation complicated by graft-versus-host disease and confounded by incidental transfusion-associated macrochimerism. Transfusion 2008; 48:2190-6. [DOI: 10.1111/j.1537-2995.2008.01835.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Weng FL, Pancoska C, Patel AM. Fatal graft-versus-host disease presenting as fever of unknown origin in a pancreas-after-kidney transplant recipient. Am J Transplant 2008; 8:881-3. [PMID: 18294353 DOI: 10.1111/j.1600-6143.2008.02150.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants.
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Affiliation(s)
- F L Weng
- Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, NJ, USA.
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Kohler S, Pascher A, Junge G, Sauer IM, Nagy M, Schönemann C, Koch M, Neumann U, Pratschke J, Neuhaus P. Graft versus host disease after liver transplantation - a single center experience and review of literature. Transpl Int 2008; 21:441-51. [PMID: 18266778 DOI: 10.1111/j.1432-2277.2007.00625.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Graft versus host disease (GvHD) after liver transplantation has an incidence of 0.1-1%. It is an infrequent but severe and mostly lethal complication. Approximately, 80 cases have been reported in literature so far. A single center experience is reported retrospectively. We performed a retrospective analysis of 1815 liver transplants in our center, transplanted over a period of 17 years. Five patients (5/1815 = 0.28%) with histologically diagnosed GvHD were included in the analysis. Onset of GvHD was between postoperative day (POD) 20 and 60. All patients developed skin rash, being the first symptom in four cases; one patient had joint pain as initial symptom. Macrochimerism was confirmed in all patients. Treatment consisted of augmentation of baseline immunosuppression (n = 4), methylprednisolone (n = 4), and T-cell depleting antibodies (n = 3). One patient received no specific therapy because of her deleterious condition. All patients died because of either haemorrhage or uncontrollable infections. In our experience, GvHD has been an extremely rare, albeit deleterious clinical condition, which was resistant to classical immunosuppressive rescue regimens.
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Affiliation(s)
- Sven Kohler
- Department of Visceral and Transplant Surgery, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
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