Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy

Purpose: Multipotential mesenchymal stem cells (MSCs) are found in human bo ne marrow and are shown to secrete hematopoietic cytokines and support hema topoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoi etic stem cells, and we investigated the feasibility, safety, and hematopoi etic effects of culture-expanded MSCs in breast cancer patients receiving a utologous peripheral-blood progenitor-cell (PBPC) infusion. Patients and Methods: We developed an efficient method of isolating and cul ture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MS C infusion and daily granulocyte colony-stimulating factor. Results: Human MSCs were successfully isolated from a mean +/- SD of 23.4 /- 5.9 mL of bone marrow aspirate from all patients. Expansion cultures gen erated greater than 1 x 10(6) MSCs/kg for all patients over 20 to 50 days w ith a mean potential of 5.6 to 36.3 x 10(6) MSCs/kg after two to six passag es, respectively. Twenty-eight patients were infused with 1 to 2.2 x 10(6) expanded autologous MSCs/kg intravenously over 15 minutes. There were no to xicities related to the infusion of MSCs. Clonogenic MSCs were detected in venous blood up to 1 hour after infusion in 13 of 21 patients (62%). Median time to achieve a neutrophil count greater than 500/mu L and platelet coun t greater than or equal to 20,000/mu L untransfused was 8 days (range, 6 to 11 days) and 8.5 days (range, 4 to 19 days), respectively. Conclusion: This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoi etic recovery suggests that MSC infusion after myeloablative therapy may ha ve a positive impact on hematopoiesis and should be tested in randomized tr ials. (C) 2000 by American Society of Clinical Oncology.