Short-term low-dose corticosteroid prophylaxis reduces the incidence of graft-vs.-host disease in patients who undergo allogeneic haploidentical stem-cell transplantation to treat hematologic neoplasms, according to a report published online April 18 in the Journal of Clinical Oncology.
The key to selecting patients most likely to benefit from the corticosteroid therapy is to identify those at high risk for graft-vs.-host disease (GVHD) using two biomarkers: high levels of CD56bright natural killer cells in allogeneic grafts or high CD4:CD8 ratios in bone marrow grafts, according to Dr. Ying-Jun Chang of Peking University People’s Hospital, Beijing, and associates.
The investigators performed an open-label trial involving 228 patients aged 15-60 years treated at a single medical center during an 18-month period for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, or other hematologic neoplasms. Using the two biomarkers, the patients were categorized as either high or low risk for developing GVHD. They were randomly assigned to three study groups: 72 high-risk patients who received short-term low-dose corticosteroids, 73 high-risk patients who received usual care, and 83 low-risk patients who received usual care.
The cumulative 100-day incidence of acute grade-II to grade-IV GVHD was significantly lower in the high-risk patients who received prophylaxis (21%) than in the high-risk patients who did not receive prophylaxis (48%). In fact, corticosteroids decreased the rate of GVHD so that it was comparable with that in the low-risk patients (26%), Dr. Chang and associates said (J Clin Oncol. 2016 Apr 18. doi: 10.1200/JCO.2015.63l.8817).
Moreover, in the high-risk patients the median interval until GVHD developed was 25 days for those who took corticosteroids, compared with only 15 days for those who did not. Median times to myeloid recovery and platelet recovery were significantly shorter for high-risk patients who received corticosteroids than for either of the other study groups. However, 3-year overall survival and leukemia-free survival were comparable among the three study groups.
The short-term low-dose regimen of corticosteroids did not raise the rate of adverse events, including infection, which suggests that it is preferable to standard corticosteroid regimens in this patient population. The incidences of cytomegalovirus or Epstein-Barr virus reactivation, post-transplantation lymphoproliferative disorder, hemorrhagic cystitis, bacteremia, and invasive fungal infections were comparable among the three study groups. Of note, the incidences of osteonecrosis of the femoral head and secondary hypertension were significantly lower among high-risk patients who received corticosteroid prophylaxis than among those who did not.
“These results provide the first test, to our knowledge, of a novel risk-stratification-directed prophylaxis strategy that effectively prevented acute GVHD among patients who were at high risk for GVHD, without unnecessarily exposing patients who were at low risk to excessive toxicity from additional immunosuppressive agents,” Dr. Chang and associates said.