Mesenchymal Stromal Cells for Treating Steroid-Resistant Acute and Chronic Graft Versus Host Disease: A Multicenter Compassionate Use Experience

Abstract

Graft versus host disease (GVHD) is a severe complication after allogenic hematopoietic cell transplantation (HSCT). Several clinical trials have reported the use of mesenchymal stromal cells (MSCs) for the treatment of GVHD. In March 2008, the Andalusian Health Care System launched a compassionate use program to treat steroid-resistant GVHD with MSC. Clinical-grade MSC were obtained under GMP conditions. MSC therapy was administered intravenously in four separate doses of 1 × 106 cells/kg. Sixty-two patients, 45 males (7 children) and 17 females (2 children), received the treatment. Patients had a median age of 39 years (range: 7–66) at the time of the allogenic HSCT. The overall response was achieved in 58.7% of patients with acute (a)GVHD. Two years’ survival for aGVHD responders was 51.85%. The overall response for patients with chronic (c)GVHD was 65.50% and the 2-year survival rate for responders was 70%. Age at the time of HSCT was the only predictor found to be inversely correlated with survival in aGVHD. Regarding safety, four adverse events were reported, all recovered without sequelae. Thus, analysis of this compassionate use experience shows MSC to be an effective and safe therapeutic option for treating refractory GVHD, resulting in a significant proportion of patients responding to the therapy.

Ruxolitinib in patients with graft versus host disease (GvHD): findings from a compassionate use program

“…CU programs are extensive sources of patient information for investigating new therapies for GvHD in a real-world clinical setting [ 27 – 29 ]. This study is the first analysis of real-world data from the global ruxolitinib CU program for patients with corticosteroid-refractory GvHD.…”

Evaluation of safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells in pediatric bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT)

“…While the application of MSC therapy in the management of aGVHD is well-discussed in the literature [ 38 – 40 , 62 , 63 ], evidence of its efficacy for cGVHD is scarce. By and all, the outcomes have been promising, even in those with severe steroid-refractory disease [ 64 – 67 ]. However, some studies have documented conflicting observations on the response of cGVHD (including lung involvement) to autologous BM- [ 68 ] and allogeneic umbilical cord-derived MSCs [ 69 ].…”

Mesenchymal stromal cells, metabolism, and mitochondrial transfer in bone marrow normal and malignant hematopoiesis

“…Co-transplantation of BM-MSCs in the context of cord blood HSC transplantation accelerates short-term hematopoietic engraftment ( de Lima et al, 2012 ). A positive impact of the MSC co-transplant has also been observed in lymphoma and myeloma patients with an increased production in memory and naïve T cells ( Batorov et al, 2015 ) and reducing GvHD after allogeneic HSCT ( Burnham et al, 2020 ; Macías-Sánchez et al, 2022 ), possibly through cytokine-mediated promotion of CD5 + B-cell production and downregulation of NK cells, CD4 + T cells, and/or macrophages ( Lin et al, 2023 ). MSCs can also compromise the immune cell activity in leukemia patients, which may associate with disease recurrence after HSCT and MSC co-transplantation ( Ning et al, 2008 ).…”