Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients.

By H. Lazarus, O. Koç, S. Devine, P. Curtin, R. Maziarz, H. Holland, E. Shpall, P. McCarthy, K. Atkinson, B. Cooper and 5 more. Biology of Blood and Marrow Transplantation, 2005

826 citations recorded by the source corpus.

Mesenchymal stem cells (MSCs) are found in a variety of tissues, including human bone marrow; secrete hematopoietic cytokines; support hematopoietic progenitors in vitro; and possess potent immunosuppressive properties. We hypothesized that cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs) from HLA-identical sibling donors after myeloablative therapy could facilitate engraftment and lessen graft-versus-host disease (GVHD); however, the safety and feasibility of this approach needed to be established. In an open-label, multicenter trial, we coadministered culture-expanded MSCs with HLA-identical sibling-matched HSCs in hematologic malignancy patients. Patients received either bone marrow or peripheral blood stem cells as the HSC source. Patients received 1 of 4 study-specified transplant conditioning regimens and methotrexate (days 1, 3, and 6) and cyclosporine as GVHD prophylaxis. On day 0, patients were given culture-expanded MSCs intravenously (1.0-5.0 x 10(6)/kg) 4 hours before infusion of either bone marrow or peripheral blood stem cells. Forty-six patients (median age, 44.5 years; range, 19-61 years) received MSCs and HLA-matched sibling allografts. MSC infusions were well tolerated, without any infusion-related adverse events. The median times to neutrophil (absolute neutrophil count > or = 0.500 x 10(9)/L) and platelet (platelet count > or = 20 x 10(9)/L) engraftment were 14.0 days (range, 11.0-26.0 days) and 20 days (range, 15.0-36.0 days), respectively. Grade II to IV acute GVHD was observed in 13 (28%) of 46 patients. Chronic GVHD was observed in 22 (61%) of 36 patients who survived at least 90 days; it was extensive in 8 patients. Eleven patients (24%) experienced relapse at a median time to progression of 213.5 days (range, 14-688 days). The probability of patients attaining disease- or progression-free survival at 2 years after MSC infusion was 53%. Cotransplantation of HLA-identical sibling culture-expanded MSCs with an HLA-identical sibling HSC transplant is feasible and seems to be safe, without immediate infusional or late MSC-associated toxicities. The optimal MSC dose and frequency of administration to prevent or treat GVHD during allogeneic HSC transplantation should be evaluated further in phase II clinical trials.

Subfields: Genetics, Hematology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/7700b21ed249dc9ea9f1ba0b8362c5de8893ffb8

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In Genetics

1. D. Prockop
2. W. Fibbe
3. N. Singer
4. A. Caplan
5. M. Kay
6. J. Karp
7. Andrea Augello
8. C. De Bari

In Hematology

1. W. Fibbe
2. D. Prockop
3. A. Caplan

In Pulmonary and Respiratory Medicine

1. W. Fibbe
2. Antonio Giordano
3. A. Caplan

Citations in the corpus

• Mesenchymal stem cell perspective: cell biology to clinical progress (2019, background): “host disease in the recipients, not more.(112,113) This unexpected important medical benefit of allogeneic MSC treatment has been explored extensively to date.”
• Mesenchymal stromal cells: sensors and switchers of inflammation. (2013, neutral): “, 2008) but has little effect on GvHD (Lazarus et al., 2005).”
• From the laboratory bench to the patient's bedside: An update on clinical trials with mesenchymal stem cells (2007, background): “These results suggest that introducing culture-expanded MSCs together with HSC transplantation is a safe procedure and could potentially reduce transplant side effects and enhance marrow recovery after myeloablative treatment (Lazarus et al., 2005).”
• Sarcoma Derived from Cultured Mesenchymal Stem Cells (2007, background): “The beneficial effects of MSCs are being tested clinically in attempts to improve hematopoietic engraftment [ 9 ], to treat osteogenesis imperfecta [10], graft-versus-host disease [11], and autoimmune diseases [12–14], and to deliver therapy for malignancies [15, 16].”
• Mesenchymal stem cells: mechanisms of inflammation. (2011, methodology): “F or p er so na l u se o nl y. Table 1 Clinical trials registered as of April 19, 2010, at http://clinicaltrials.gov Sponsor Indication Phase Number of patients and study identification number Completed Osiris Therapeutics Moderate to severe Crohn’s disease 2 10, NCT00294112 Shaheed Beheshti Medical”
• Safety of Cell Therapy with Mesenchymal Stromal Cells (SafeCell): A Systematic Review and Meta-Analysis of Clinical Trials (2012, methodology): “[17,18,26,27,29,31,33,35] Five studies explicitly reported and separated serious from non-serious adverse events; [13,14,20,24,46] two of these referenced a standardized approach to detailing adverse events developed by other organizations.”