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.
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. 
Graft versus host disease (GVHD) is a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT) which continues to limit the broader application of this therapy.
Occurs when donor T cells respond to host histoincompatible antigens on the host tissues.
Current consensus is that clinical manifestations guide whether the signs and symptoms of GVHD are acute, chronic, or an overlap syndrome.
Acute GVHD classically targets the skin, liver, and gastrointestinal tract. In contrast, chronic GVHD can involve almost any organ.
Acute GVHD prophylaxis usually comprises a calcineurin-based inhibitor such as cyclosporine or tacrolimus (that blocks 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, physical therapy, nutritional status, pain control, and monitoring of drug-drug interactions and drug-related adverse effects.
Graft versus host disease (GVHD) is a major complication following allogeneic hematopoietic 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 gastrointestinal 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 characterized by clinical features that resemble a combination of both acute and chronic GVHD.
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
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
- 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
- low performance status score
- low socioeconomic status
1st investigations to order
- serum electrolytes
- liver functions tests
- 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
- barium swallow or upper GI endoscopy
- 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan
hematopoietic cell transplantation (HCT) recipient
acute: grade I
acute: grade II-IV
Sung Won Choi, MD, MS
Department of Pediatrics and Communicable Diseases
Division of Pediatric Hematology Oncology/Blood and Marrow Transplantation
University of Michigan
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
LR declares that she has no competing interests.
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.
Corey Cutler, MD, MPH, FRCPC
Associate Professor of Medicine
Harvard Medical School
Dana-Farber Cancer Institute
CC declares that he has no competing interests.
Waseem Qasim, BMedSci (Hons), MBBS, MRCP (UK), MRCPCH, PhD
Institute of Child Health
Consultant in Paediatric Immunology & Bone Marrow Transplantation
Great Ormond Street Hospital
WQ declares that he has no competing interests.
- Drug rash
- Radiation rash
- Bacterial gastroenteritis
- Long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers
- Guideline on dental management of pediatric patients receiving chemotherapy, hematopoietic cell transplantation, and/or radiation
- Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer