Graft versus host disease

Last reviewed: 25 Apr 2022
Last updated: 08 Feb 2022
08 Feb 2022

US FDA approves abatacept for preventing acute graft versus host disease

Abatacept, a selective T-cell costimulation modulator, has been approved by the US Food and Drug Administration (FDA) for preventing acute graft versus host disease (GVHD) in adults and children aged ≥2 years undergoing allogeneic hematopoietic cell transplantation (HCT) from a matched or 1 allele-mismatched unrelated donor (in combination with standard GVHD prophylaxis comprising a calcineurin inhibitor and methotrexate).

Abatacept is the first FDA-approved drug for preventing acute GVHD.

In a phase 2 randomized trial, the addition of abatacept to standard prophylaxis with a calcineurin inhibitor and methotrexate numerically reduced rates of severe (grade III or IV) acute GVHD, and significantly improved severe acute GVHD-free survival, in patients with hematologic malignancies who had undergone HCT from an HLA-matched (8/8) unrelated donor.[55]

The benefit attributable to abatacept appeared to be greater in a comparison of single HLA-mismatched (7/8) unrelated donor patients with a registry-based matched cohort. [55]

See Management: approach

See Management: treatment algorithm

See Management: prevention

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • allogeneic hematopoietic cell transplantation (HCT) recipient
  • unrelated donor
  • multiparous female donor
  • diffuse maculopapular rash with fever
  • nausea, abdominal pain, and profuse diarrhea
More key diagnostic factors

Other diagnostic factors

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

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
  • absent or suboptimal GVHD prophylaxis
  • non-Asian or non-Hispanic ethnicity
  • cytomegalovirus (CMV) seropositive
  • splenectomy
  • low performance status score
  • low socioeconomic status
More risk factors

Diagnostic investigations

1st investigations to order

  • CBC
  • serum electrolytes
  • liver functions tests
  • urinalysis
  • urine culture
  • blood culture
  • stool culture
  • viral polymerase chain reaction (PCR)
More 1st investigations to order

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 upper GI endoscopy
  • 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan
More investigations to consider

Treatment algorithm

INITIAL

hematopoietic cell transplantation (HCT) recipient

ACUTE

acute: grade I

acute: grade II-IV

ONGOING

chronic

Contributors

Authors

Sung Won Choi, MD, MS
Sung Won Choi

Associate Professor

Department of Pediatrics and Communicable Diseases

Division of Pediatric Hematology Oncology/Blood and Marrow Transplantation

University of Michigan

Ann Arbor

MI

Disclosures

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

Lyndsey Runaas, MD
Lyndsey Runaas

Assistant Professor, Hematology and Oncology

Division of Hematology/Oncology

Medical College of Wisconsin

Milwaukee

WI

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 topic. PR is an author of a number of references cited in this topic.

Peer reviewers

Corey Cutler, MD, MPH, FRCPC

Associate Professor of Medicine

Harvard Medical School

Dana-Farber Cancer Institute

Boston

MA

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

UK

Disclosures

WQ declares that he has no competing interests.

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