OBJECTIVES: Success rates of allogenic haematopoietic stem cell transplantation are tarnished by high incidences of acute graft-versus-host disease (aGvHD). For those patients not responding to first-line steroid therapy, there is no approved second-line treatment available and long-term outcome remains poor. Since 2004, mesenchymal stromal cells (MSC) are studied as treatment for steroid-refractory aGvHD (SR-aGvHD) in a number of phase II trials. However, no disease model (DM) exists to integrate and extrapolate currently available evidence on MSC treatment. We aimed at developing such a DM to assess the long-term costs and effects of MSC treatment.

METHODS: The DM was developed in collaboration with experts in the field haematology-oncology which are all part of EU sponsored research initiate to investigate the usefulness of MSC for the treatment of aGvHD (RETHRIM). Model input parameters for transition and survival estimates were informed by patient-level data of 12 phase II clinical trials. Several parametric distributions were used to estimate long-term survival rates after MSC treatment. Sub-group analyses were conducted.

RESULTS: The DM consists of nine health stages: (1) treatment response, (2) treatment failure, (3) tapering schedule of steroids and/or other immune-suppressive drugs, (4) 3^rd-line therapy, (5) sustained response, (6) relapse/persistent aGvHD, (7) chronic GvHD, (8) relapse and adverse events of hematologic disease, and (9) death. Data of 209 patients (median age: 30.5 years; range = 0.4 – 69.0) was recorded. Median survival time for all observations with valid survival data (n = 110) was 2.5 years after treatment. Further results include: transition rates from aGvHD stages II-IV to aGvHD stages 0, I, II, III, and IV, subgroup analysis (female/male, several age groups), as well as extrapolated survival estimates of different parametric functions.

CONCLUSIONS: We created a DM that can eventually aid clinical decision-making and serve as a template for future model-based cost-effectiveness studies.