Multipotent Adult Progenitor Cells (Multistem®) Enhance Bone Marrow Recovery After Ablative Allogeneic Stem Cell Transplant

Adherent stem cells, exemplified by mesenchymal stromal cells (MSC), are being increasingly evaluated in the hematopoietic stem cell transplant (HSCT) setting as a potential means to prevent or ameliorate acute graft-versus-host-disease. Anecdotal data suggest MSC can support hematopoiesis after HSCT. The potential role of MSC to enhance hematopoiesis is also being investigated, particularly with ex vivo expansion of low dose stem cell donors such as cord blood. However, the effect of infused MSC on bone marrow recovery after ablative HSCT remains unclear. A matched cohort analysis was performed comparing patients in a Phase I dose-escalation trial evaluating maximum-tolerated single or repeated dose of allogeneic Multistem®, an adherent multipotent adult progenitor cell (MAPC) product, with a control population undergoing HSCT without MAPC administration. Patients surviving at least 50 days post-HSCT without relapse were eligible for analysis, and matched with a control cohort by disease and transplant characteristics. Time to neutrophil (ANC ≥500/ul for 3 consecutive days) and platelet (sustained platelets ≥50,000 without transfusion) engraftment, as well as total bone marrow cellularity after HSCT on days 28 and 100 by blinded double pathologist independent review, were assessed. Unpaired t test was applied to compare days of engraftment and marrow cellularities. 23 patients undergoing conventional ablative allogeneic HSCT with MAPC exposure in addition to their matched pair allogeneic HSCT recipients were eligible for analysis (Table 1). The median time to neutrophil engraftment was significantly shortened among patients receiving MAPC, compared to control patients, occurring at day 14 (range 11-23) and 17 (range 13-23), respectively (p = 0.016). There was no significant difference in time to platelet engraftment. In 16/23 (70%) and 10/14 (71%) evaluable patients receiving MAPC, total marrow cellularity was ≥ control patients at days 28 and 100. There was a trend towards significantly increased marrow cellularity at these time points among recipients of MAPC (p = 0.077 and p = 0.061). The infusion of MAPC progenitors in patients receiving allogeneic HSCT is associated with a shorter time to neutrophil engraftment. Total bone marrow cellularity at days 28 and 100 appears enhanced among patients receiving MAPC. These preliminary findings support further analysis of a role for infused MSC in facilitating bone marrow recovery in the HSCT-setting.Table 1MAPC RecipientsControl CohortNumber of Patients2323Age in years58 (20-63)53 (24-65)Gender: Male1621 Female72Disease: AML138 MDS48 ALL33 CML13 Other21Donor Type: Related1112 Unrelated1211Stem Cell Source: Bone Marrow00 Peripheral Blood2323HLA-Match: Matched2221 Single-Antigen Mismatch12Conditioning: Bu/Cy914 TBI/Cy59 Flu/Mel90GVHD Prophylaxis: FK506/MTX2323 Open table in a new tab