How I treat refractory acute GVHD

Abstract

Graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with considerable morbidity and mortality, particularly in patients who do not respond to primary therapy, which usually consists of glucocorticoids (steroids). Approaches to therapy of acute GVHD refractory to "standard" doses of steroids have ranged from increasing the dose of steroids to the addition of polyclonal or monoclonal antibodies, the use of immunotoxins, additional immunosuppressive/chemotherapeutic interventions, phototherapy, and other means. While many pilot studies have yielded encouraging response rates, in most of these studies long-term survival was not improved in comparison with that seen with the use of steroids alone. A major reason for failure has been the high rate of infections, including invasive fungal, bacterial, and viral infections. It is difficult to conduct controlled prospective trials in the setting of steroid-refractory GVHD, and a custom-tailored therapy dependent upon the time after HCT, specific organ manifestations of GVHD, and severity is appropriate. All patients being treated for GVHD should also receive intensive prophylaxis against infectious complications.

Figure 1

Management of acute GVHD. ¹Patients with grade IIa GVHD may respond to MP, 1 mg/kg, possibly combined with beclomethasone, 1-2 mg 4 times a day, and budesonide, 3 mg twice a day. In patients with grades IIb to IV GVHD, the starting dose of MP should probably be 2 mg/kg (with or without the addition of beclomethasone and budesonide). (Grade IIa is defined as skin rash of < 50% body surface area, not progressing rapidly within the first day; bilirubin < 3 mg/dL; < 20 mL nonhemorrhagic diarrhea/kg per day, without abdominal cramping. Grades IIb-IV include all cases outside the parameters defined for grade IIa.) ²The decision will likely depend upon the timing of the GVHD flare and the clinical presentation of the disease. Illustration by A. Y. Chen and H. Crawford.