Graft-versus-host disease

Last reviewed: July 2018

Last updated: March 2018

Summary

A major cause of morbidity and mortality following allogeneic haematopoietic cell transplantation (HCT), which continues to limit the broader application of this therapy.

Occurs when donor T cells respond to host antigens.

Acute and chronic forms have traditionally been defined based on the timeframe post-transplant (less than or greater than 100 days, respectively). However, current consensus is that clinical manifestations guide whether the signs and symptoms of graft-versus-host disease (GVHD) are acute, chronic, or an overlap syndrome.

Acute GVHD classically targets the skin, liver, and GI tract. In contrast, chronic GVHD can involve almost any organ.

Prophylaxis against acute GVHD usually comprises a calcineurin-based inhibitor such as ciclosporin or tacrolimus (which block T-cell activation), administered with other immunosuppressants such as low-dose methotrexate or mycophenolate.

Optimum treatment of both acute and chronic forms of GVHD is yet to be fully defined, but current practice usually involves the use of systemic corticosteroids with additional immunosuppressants as required, often as part of a clinical trial.

Supportive care and monitoring are vital components of chronic GVHD management with emphasis on infection prophylaxis, physiotherapy, nutritional status, pain control, and monitoring of drug-drug interactions and drug-related adverse effects.

Definition

Graft-versus-host disease (GVHD) is a major complication following allogeneic haematopoietic cell transplantation (HCT) and occurs when donor T cells respond to histoincompatible antigens on the host tissues.

Acute GVHD classically develops within the first 100 days of transplant or can occur beyond 100 days post-transplant with persistent, recurrent, or late-onset symptoms. The principle target organs include the skin, liver, and GI tract.

Chronic GVHD may emerge from acute disease (progressive type), develop following a period of resolution from acute disease (quiescent or interrupted type), or occur de novo. The manifestations can be variable, and are often similar to those seen in autoimmune diseases.

Overlap syndrome is characterised by clinical features that resemble a combination of both acute and chronic GVHD.

History and exam

Key diagnostic factors

allogeneic haematopoietic cell transplantation (HCT) recipient
unrelated donor
multiparous female donor
diffuse maculopapular rash with fever
nausea, abdominal pain, and profuse diarrhoea

Full details

Other diagnostic factors

day +14 after HCT
cyclophosphamide + total body irradiation (Cy/TBI) conditioning regimen
peripheral blood stem cells as donor source
suboptimal GVHD prophylaxis
new-onset painful mouth sores
hyperpigmented skin lesions
dry, gritty, and painful eyes
dry, irritated vagina and vulva
jaundice
hepatomegaly
scleroderma

Full details

Risk factors

HLA disparity
recipient or donor in older age group
female donor with male recipient
multiparous female donor
advanced malignant condition
high-intensity conditioning radiation regimen
peripheral blood stem cells as source of transplant
lack of GVHD prophylaxis
non-Asian or non-Hispanic ethnicity
cytomegalovirus (CMV) seropositive
splenectomy
low performance status score
low socioeconomic status

Full details

Diagnostic investigations

1st investigations to order

FBC
serum electrolytes
liver functions tests
urinalysis
urine culture
blood culture
stool culture
viral polymerase chain reaction (PCR)

Full details

Investigations to consider

CT abdomen
Doppler ultrasound of the liver
tissue biopsy (skin, liver, GI tract, oral lesions, or lung)
pulmonary function tests
high-resolution CT chest
bronchoalveolar lavage (BAL) and culture
echocardiogram
barium swallow or endoscopy
FDG-PET scan

Full details

Treatment algorithm

INITIAL

Contributors

Authors VIEW ALL 

Sung Choi, MD, MS

Assistant Professor

Department of Pediatrics and Communicable Diseases

Division of Pediatric Hematology Oncology/Blood and Marrow Transplantation

University of Michigan

Ann Arbor

Disclosures

SC is an author of a number of references cited in this monograph.

Lyndsey Runaas, MD

Fellow, Hematology and Oncology

Division of Hematology/Oncology

University of Michigan

Ann Arbor

Disclosures

LR declares that she has no competing interests.

Acknowledgements

Dr Sung Choi and Dr Lyndsey Runaas would like to gratefully acknowledge Dr Pavan Reddy, a previous contributor to this monograph. PR is an author of a number of references cited in this monograph.

Peer reviewers VIEW ALL 

Corey Cutler, MD, MPH, FRCPC

Associate Professor of Medicine

Harvard Medical School

Dana-Farber Cancer Institute

Boston

Disclosures

CC declares that he has no competing interests.

Waseem Qasim, BMedSci (Hons), MBBS, MRCP (UK), MRCPCH, PhD

Senior Lecturer

Institute of Child Health

Consultant in Paediatric Immunology & Bone Marrow Transplantation

Great Ormond Street Hospital

London

Disclosures

WQ declares that he has no competing interests.

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Graft-versus-host disease

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

haematopoietic cell transplantation (HCT) recipient

acute: grade I

acute: grade II-IV

chronic

Contributors

Authors VIEW ALL 

Sung Choi, MD, MS

Disclosures

Lyndsey Runaas, MD

Disclosures

Acknowledgements

Peer reviewers VIEW ALL 

Corey Cutler, MD, MPH, FRCPC

Disclosures

Waseem Qasim, BMedSci (Hons), MBBS, MRCP (UK), MRCPCH, PhD

Disclosures

Differentials

Guidelines

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