ABSTRACT
Application of mesenchymal stem cells (MSC) enables a novel approach to the therapy of graft- vs-host disease (GVHD) after hematopoietic stem cell transplantation. Herein we present our preliminary experience with the use of allogeneic bone marrowâderived MSC in 9 pediatric patients after hematopoietic transplantation complicated by severe acute or chronic GVHD (aGVHD, cGVHD) resistant to steroids and second-line immunosuppressants. The MSC therapy was applied concurrently with immunosuppressive treatment in 5 patients as a single infusion, in four patients as 2-6 infusions. The median dose of cells per infusion was 1.9 × 106/kg of recipient body weight (range, 0.1-6.5 × 106/kg). The median quantity of cells applied to patients was 1.2 × 106/kg (range, 0.2-30.9 × 106/kg). We did not observe any adverse symptoms of MSC therapy. Overall, partial, or complete remission (PR and CR, respectively) was obtained in 56% of patients after the first MSC infusions, and 44% after completing therapy. In those with skin involvement 50% achieved permanent CR, 38% in those with gastrointestinal manifestations, and 33% in those with liver GVHD. Three patients with overlap syndrome had amelioration, but none had permanent remission. Long-term improvement after consecutive MSC doses was observed in 3 patients. In the 4- to 8-year follow-up, 3 patients are alive and 2 have attained permanent remission. Six patients died during follow-up: 4 with aGVHD and 2 with infectous complications. Co-treatment of streoid-resistant GVHD with MSC and conventional immunosuppression can improve the outcome, although therapy regimens remain to be established.
