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Introduction: Early reports demonstrated the safety of adherent mesenchymal stromal cell (MSC) infusions in the hematopoietic stem cell transplantation (HCT) setting, as well as clinical efficacy for treatment of steroid refractory acute graft-versus-host disease (GVHD); however, two large, Phase III randomized, placebo-controlled trials of MSC for initial therapy or steroid refractory GVHD failed to meet their primary endpoints of durable complete response. Subset analyses demonstrated efficacy in selected patient populations, contributing to recent approvals of MSC for pediatric patients in Canada and New Zealand., Areas Covered: In this review, we discuss the biologic and immunomodulatory properties of MSC and potential mechanisms involved. We review the results of prior clinical trials incorporating MSC for GVHD treatment or prophylaxis, the recent approvals in Canada and New Zealand, as well as future directions in the field., Expert Opinion: The role of MSC infusions, in the prophylaxis and/or treatment of GVHD after HCT, continues to be under active investigation. Whether, and how, to incorporate MSC infusions is unclear, and ongoing questions include the source tissue type and culture methods, the timing and dosage of MSC product infusions, as well as the optimal clinical trial design and endpoints for assessment of clinical response.

Purpose: Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved., Patients and Methods: Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk., Results: Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL., Conclusion: This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.