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A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease
1Division of Hematologic Malignancies/BMT, The Johns Hopkins Oncology Center, Baltimore 21231, USA. gakpek@jhmi.edu
Insights
High-dose pulse steroids (PS) offer a well-tolerated option for severe chronic graft-versus-host disease (cGVHD) refractory to other treatments. This regimen achieved rapid clinical responses in most patients, though long-term maintenance strategies require further investigation.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Corticosteroids are crucial for managing active chronic graft-versus-host disease (cGVHD).
- Optimal dosing and administration schedules for corticosteroids in cGVHD remain undetermined.
- Severe refractory cGVHD presents significant treatment challenges.
Purpose of the Study:
- To evaluate the efficacy and safety of a high-dose pulse steroid regimen (PS) for severe refractory cGVHD.
- To assess response rates, progression, and treatment discontinuation following PS therapy.
- To determine the tolerability of the PS regimen in patients with advanced cGVHD.
Main Methods:
- Retrospective review of 61 patients with severe refractory cGVHD treated with methylprednisolone (10 mg/kg/day for 4 days) followed by tapering doses.
- All patients received additional immunosuppressive therapy post-PS.
- Evaluation of response, progression, survival, and treatment discontinuation in 56 evaluable patients.
Main Results:
- A major response (48%) or minor response (27%) was observed in 75% of patients treated with PS.
- The 1-year and 2-year survival probabilities were 88% and 81%, respectively.
- Twenty-four percent of responders discontinued immunosuppressive therapy, with a 2-year discontinuation probability of 27%.
- The treatment was well-tolerated with no serious adverse events.
Conclusions:
- High-dose pulse steroids (PS) provide a well-tolerated and effective approach for rapid clinical response in refractory cGVHD.
- PS demonstrates promising survival and treatment discontinuation rates in heavily pre-treated patients.
- Further research is needed to optimize long-term efficacy, potentially through combination therapies.
Abstract:
Corticosteroids remain essential for controlling active chronic graft-versus-host disease (cGVHD). However, the optimum dose and administration schedule is unknown. We have reviewed our results in 61 patients with severe refractory cGVHD who were treated with a high-dose pulse steroid regimen (PS) consisting of methylprednisolone at 10 mg/kg per day for 4 consecutive days, with subsequent tapering doses. After 4 days, all patients received a course of additional immunosuppressive therapy. The median age of the 56 patients who were evaluable for response was 32 years (range, 0.2-57 years). Patients had failed a median of 2 (range, 1-5) treatments prior to the PS. The median follow-up for 45 surviving patients after PS was 1.5 years. The probability of survival at 1 year and 2 years after PS was 88% (95% confidence interval [CI], 76%-95%) and 81% (95% CI, 65%-91%), respectively. Twenty-seven patients (48%) showed a major response to PS with substantial improvement of cGVHD manifestations, including softening of the skin, increased range of motion, and improved performance status; 15 patients (27%) showed a minor response, defined as improvement in some but not all symptoms of cGVHD. Of the 42 responders, 21 (50%) had progression of their cGVHD afterwards. The median time to progression was 1.9 years. The probability of progression at 1 and 2 years after PS was 36% (95% CI, 23%-53%) and 54% (95% CI, 38%-71%), respectively. The probability of progression at 1 year was 25% (95% CI, 12%-47%) and 55% (95% CI, 32%-81%) for patients who had major and minor response, respectively (hazard ratio, 2.13). Ten of the 42 responders (24%) were able to discontinue all systemic immunosuppressive treatments. The probability of discontinuation at 1 and 2 years after PS was 9% (95% CI, 3%-25%) and 27% (95% CI, 15%-48%), respectively. The treatment was well tolerated with no serious adverse events. Our results suggest that PS is a well-tolerated regimen for achieving rapid clinical response in the majority of patients with cGVHD who failed on multiple previous therapies. Further studies are warranted to maintain the efficacy of this regimen by combining with new active agents in cGVHD.