Graft versus host disease

Acute graft versus host disease (GVHD)

Using the Minnesota acute GVHD risk score to categorize a relatively recent patient cohort (2007-2016), overall response rates (complete response plus partial response) for patients with standard risk acute GVHD and high-risk cute GVHD were 68% and 49% at day 56, respectively.[87]MacMillan ML, DeFor TE, Holtan SG, et al. Validation of Minnesota acute graft-versus-host disease risk score. Haematologica. 2020;105(2):519-24. https://pmc.ncbi.nlm.nih.gov/articles/PMC7012472 http://www.ncbi.nlm.nih.gov/pubmed/31320554?tool=bestpractice.com ​ Patients with high-risk acute GVHD were at increased risk for 2 year transplant-related mortality and overall mortality compared with patients with a standard risk GVHD. Of note, the Minnesota GvHD Risk Score is intended to explore GVHD risk, inform upfront acute GVHD therapy, and to improve risk stratification in clinical trials.

Once acute GVHD occurs, the most important predictor of long-term survival is the primary response to therapy. In patients who do not respond completely to initial therapy, the risk of morbidity and mortality increases significantly.[171]Leisenring WM, Martin PJ, Petersdorf EW, et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood. 2006 Jul 15;108(2):749-55. http://bloodjournal.hematologylibrary.org/cgi/content/full/108/2/749 http://www.ncbi.nlm.nih.gov/pubmed/16537799?tool=bestpractice.com [172]Van Lint MT, Milone G, Leotta S, et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood. 2006 May 15;107(10):4177-81. http://bloodjournal.hematologylibrary.org/cgi/content/full/107/10/4177 http://www.ncbi.nlm.nih.gov/pubmed/16449522?tool=bestpractice.com ​ Lack of response or lack of improvement following 3-7 days of corticosteroid therapy is associated with poor prognosis, primarily due to life-threatening opportunistic infections and/or multi-organ dysfunction.[173]Bolanos-Meade J, Vogelsang GB. Novel strategies for steroid-refractory acute graft-versus-host disease. Curr Opin Hematol. 2005 Jan;12(1):40-4. http://www.ncbi.nlm.nih.gov/pubmed/15604890?tool=bestpractice.com For severe grade III-IV GVHD, survival rates beyond 1 year are approximately 10% to 15%.

In some cases, withdrawal of corticosteroid therapy can lead to a flare of acute GVHD and/or evolve into chronic GVHD. The exact rate of flares is unpredictable, but it is higher in mismatched or unrelated donor hematopoietic cell transplantations (HCTs).

The outlook for patients who require second-line treatments is poor, and new approaches to prophylaxis, initial and salvage therapy are needed. Furthermore, it is difficult to predict which patients will respond to certain therapeutic modalities.

Chronic GVHD

The overall prognosis for patients with chronic GVHD is primarily dependent on the appropriate diagnosis, treatment, prevention of treatment-associated complications, and long-term care of organs affected. The leading cause of death is treatment-associated complications, particularly life-threatening opportunistic infections.

Despite aggressive management, overall survival following diagnosis and treatment has not improved significantly during the past 30 years.[8]Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003 Apr;9(4):215-33. http://www.ncbi.nlm.nih.gov/pubmed/12720215?tool=bestpractice.com [174]Goerner M, Gooley T, Flowers ME, et al. Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias. Biol Blood Marrow Transplant. 2002;8(1):47-56. http://www.ncbi.nlm.nih.gov/pubmed/11858190?tool=bestpractice.com [175]Baird K, Pavletic SZ. Chronic graft versus host disease. Curr Opin Hematol. 2006 Nov;13(6):426-35. http://www.ncbi.nlm.nih.gov/pubmed/17053454?tool=bestpractice.com ​ In an analysis of 668 patients treated for chronic GVHD, the cumulative incidence of nonrelapse mortality at 2 years was 16% and overall survival at 2 years was 74%.[176]Flowers MED, Storer B, Carpenter P, et al. Treatment change as a predictor of outcome among patients with classic chronic GVHD. Biol Blood Marrow Transplant. 2008 Dec;14(12):1380-4. http://www.ncbi.nlm.nih.gov/pubmed/19041060?tool=bestpractice.com

Treatment-related complications

Prolonged exposure to systemic corticosteroids in the treatment of acute and chronic GVHD can lead to numerous toxicities and potentially irreversible adverse effects in many organs, including hypertension, hyperglycemia, anxiety, altered mood behaviors, avascular necrosis, osteopenia, vertebral fractures, poor wound healing, central obesity, myopathy, and skin atrophy with local depigmentation and telangiectasias. In addition, GVHD-mediated organ damage also contributes to significant morbidity and mortality.