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 haematopoietic 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 randomised 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 haematologic 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]
Summary
Definition
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
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
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
Diagnostic investigations
1st investigations to order
- FBC
- serum electrolytes
- liver functions tests
- urinalysis
- urine culture
- blood culture
- stool culture
- viral polymerase chain reaction (PCR)
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
Treatment algorithm
haematopoietic cell transplantation (HCT) recipient
acute: grade I
acute: grade II-IV
chronic
Contributors
Authors
Sung Won Choi, MD, MS

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

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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