Acute graft-versus-host disease

Abstract

Acute graft-versus-host disease (GVHD) is a common immune complication that can occur after allogeneic haematopoietic cell transplantation (alloHCT). Acute GVHD is a major health problem in these patients, and is associated with high morbidity and mortality. Acute GVHD is caused by the recognition and the destruction of the recipient tissues and organs by the donor immune effector cells. This condition usually occurs within the first 3 months after alloHCT, but later onset is possible. Targeted organs include the skin, the lower and upper gastrointestinal tract and the liver. Diagnosis is mainly based on clinical examination, and complementary examinations are performed to exclude differential diagnoses. Preventive treatment for acute GVHD is administered to all patients who receive alloHCT, although it is not always effective. Steroids are used for first-line treatment, and the Janus kinase 2 ( JAK2) inhibitor ruxolitinib is second-line treatment. No validated treatments are available for acute GVHD that is refractory to steroids and ruxolitinib, and therefore Nature Reviews Disease Primers | (2023) 9:27 2 0123456789();:Primer late onset acute GVHD (first episode more than 100 days after transplantation), recurrent acute GVHD (new episode of acute GVHD more than 100 days after transplantation in a patient with a history of classic acute GVHD), or persistent acute GVHD (classic acute GVHD symptoms that persist for more than 100 days after transplantation).Acute GVHD can also be graded based on severity as I (mild), II (moderate), III (severe) and IV (very severe), based on quantification of skin rash for skin acute GVHD, serum bilirubin level for liver acute GVHD, volume of diarrhoea for lower GI acute GVHD and persistent nausea for upper GI acute GVHD 9 . Grade I acute GVHD is usually not considered as clinically important given its lack of effect on patient outcome 10 ; therefore, most studies focus on grade II-IV and severe grade III-IV acute GVHD. Several systems can be used for grading acute GVHD. The MAGIC grading system is not yet used in routine clinical practice; however, it is used in this Primer as it facilitates and helps standardize acute GVHD clinical data collection, as shown by the development and validation of the electronic eGVHD application to assist health-care professionals in the assessment of acute GVHD in clinical practice 11,12 .This Primer discusses the epidemiology and pathophysiological mechanisms of acute GVHD. This Primer also discusses management, patient quality of life (QOL) and outstanding research questions including the need for more efficient prophylaxis. Epidemiology IncidenceIn the absence of effective prophylaxis, most patients develop acute GVHD; for example, in one historical series, only 19 of 93 patients did not develop acute GVHD when no prophylaxis was administered 13 . Nevertheless, acute GVHD can still occur, despite the routine use of prophylaxis after alloHCT. Acute GVHD incidence varies considerably depending, predominantly, on the degree of mismatch between HLA ...

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