Acute graft versus host disease

Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%–50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD

Low-dose MTX combined with low-dose methylprednisolone as a first-line therapy for the treatment of acute GVHD: safety and feasibility

To study the efficacy and safety of a low dose of MTX combined with a low dose of methylprednisolone (MP) as a first-line therapy in the treatment of acute GVHD (aGVHD) after allogeneic hematopoietic SCT, 32 patients received i.v. MTX at a dose of 10 mg or oral MTX at a dose of 15 mg every 3-7 days (repeated at day 3 after the first dose and then at a weekly interval) combined with a low dose of MP (0.5 mg/kg/day) until a complete or partial response was achieved, or until treatment failure or intolerable side effects occurred. The overall treatment response rate was 81% (26/32 patients) and the response rate at day 28 was 75% (24/32 patients). The response rate for GVHD involving various organs was 88% (23/26) in the skin, 75% (3/4) in the liver and 81% (9/11) in the gut. Grade 3 toxicities occurred in only three patients presenting cytopenias. The estimated survival at 2 years was 77%. From this analysis, MTX in combination with a low dose of MP appears to be a well-tolerated, effective and inexpensive regime when used as a first-line treatment for aGVHD. Bone Marrow Transplantation (2011) 46, 892-898; doi: 10.1038/bmt.2010.197; published online 16 August 2010BiophysicsOncologyHematologyImmunologyTransplantationSCI(E)PubMed7ARTICLE6892-8984