Steroid Complications in Patients with Acute Graft Versus Host Disease.

Background: High dose steroid treatment remains to be the first line therapy for acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Although effective in controlling aGVHD, high dose steroids can cause multiple serious complications which can result in increased morbidity and mortality.

Purpose: Our aim was to determine the frequency of steroid induced complications and to analyze risk factors for steroid-myopathy in patients with AML who developed grade 2 aGVHD after allogeneic HSCT.

Patients and Methods: Inclusion criteria were:

1) AML/MDS patients who received allogeneic HSCT between 1/1996 and 12/2001

2) grade 2 aGVHD treated with at least 2mg/kg of methylprednisolone

3) post transplantation overall survival at least 100 days.

Steroid induced complications reviewed were: cataracts, headaches, mood swings, hypertension, gastritis, hyperglycemia, osteopenia, myopathy, avascular necrosis, edema, hypokalemia and infections. Pre- and post-transplantation characteristics analyzed as risk factors for steroid-myopathy were: age, gender, race, history of diabetes, body mass index, HLA types, steroid use after HSCT prior to grade 2 acute GVHD and duration of steroid use for acute GVHD. Logistic regression analysis was used for risk factor evaluation. Steroid-myopathy was defined as proximal muscle weakness, atrophy and myalgia in the absence of genetic, inflammatory or drug-induced etiologies other than steroid use.

Results: 178 AML /MDS patients were transplanted during the study period. 70 patients (37 males and 33 females) with a median age of 43 (range, 21–66) were eligible for our study. Median duration of follow-up and median duration of steroid use after grade 2 aGVHD were 269 days and 127 days respectively. The number of patients and their frequency distribution of steroid induced complications were as follows: hyperglycemia, 43 (61.4%); hypertension, 35 (50%); cataracts, 10(14.3%); headaches, 7 (10%); mood swings,12(17.1%); gastritis, 7 (10%); myopathy, 32(45.7%); avascular necrosis, 1 (1.4%); edema, 22 (31.4%); hypokalemia, 52 (74.3%); bacterial infections, 55 (78.6%); viral infections, 39(55.7%); and fungal infections, 22(31.4%). For steroid-induced myopathy, male gender (RR=4.0, 95% CI=1.01–16.4, p=0.05), steroid use before acute GVHD grade II (RR=5.5, 95% CI=1.35–22.14, p=0.02) or steroid use more than 4 months after developing acute GVHD grade II (HR=6.4, 95% CI=1.38–29.94, p=0.02) were independent risk factors. 47 of 70 patients died with median overall survival of 10 months. 22 of 47 (46.8%) had steroid-myopathy and there was no increased mortality with steroid induced myopathy.

Conclusion: Steroid therapy for aGVHD after allogeneic HSCT in AML/MDS patients is associated with frequent toxicities. The possibility of identifying prognostic factors for steroid toxicities support the study and development of strategies that may ameliorate or prevent steroid induced complications.