Frédéric Baron, Rainer Storb

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Presentation transcript:

Mesenchymal Stromal Cells: A New Tool against Graft-versus-Host Disease? Frédéric Baron, Rainer Storb Biology of Blood and Marrow Transplantation Volume 18, Issue 6, Pages 822-840 (June 2012) DOI: 10.1016/j.bbmt.2011.09.003 Copyright © 2012 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 (A) Cumulative incidents of graft rejection in dogs given DLA-identical marrows after 1 Gy TBI and postgrafting immunosuppression with cyclosporin plus mycophenolate mofetil (or rapamycin) according to various additional approaches of cellular therapy [Ctrl, no additional therapy, n = 11 [138,139]; MSC, infusions of mesenchymal stem cells (1.1-1.8 × 106 MSC/kg) on days 0 and 35 after transplantation, n = 4 [137]; DLI, donor lymphocyte infusion (1-2.6 × 108 CD3/kg) around day 35 with or without preceding pentostatin, n = 9 [145]; CTLA4Ig, injection of donor PBMC before transplantation with costimulation blockade with CTLA4Ig, n = 5 [141]; and injection of donor PBMC before transplantation with costimulation blockade with CD154 antibodies, n = 6 [142]. Although CTLA4Ig (P < 0.001), CD154ab (P = 0.001), and DLI (P = 0.001) somewhat increased the rate of stable engraftment, graft rejection occurred at a similar rate in dogs given MSCs and in control dogs (P = .7). (B) Incidents of graft rejection and of GVHD as well as median number of days of survival in dogs given DLA-haploidentical marrows after 9.2 Gy TBI with or without added MSC infusions (2-3 infusions/week of 1-30 × 106 MSC/kg) after transplantation [94]. Biology of Blood and Marrow Transplantation 2012 18, 822-840DOI: (10.1016/j.bbmt.2011.09.003) Copyright © 2012 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 MSCs chimerism 1-192 (median 5) months after allogeneic bone marrow or cord blood transplantation in the study reported by Pozzi et al. [162]. MSCs were analyzed after a median of 4 passages and were positive (≥98% positivity) for CD73, CD105, CD106, CD29, CD13, and CD44 and negative (≤1%) for CD34, CD45, and CD14. MSC chimerism was determined by amelogenin assay (in case of female donor to male recipient) or by STR PCR. Pediat., pediatric recipients; BM, bone marrow; CB, umbilical cord blood; MC, mixed donor/host chimerism; FRC, full recipient chimerism. Biology of Blood and Marrow Transplantation 2012 18, 822-840DOI: (10.1016/j.bbmt.2011.09.003) Copyright © 2012 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 (A) Complete response (CR), partial response (PR), and no response (NR) rates in patients given methylprednisolone (2 mg/kg) plus MSCs (prochymalR) at the dose of 2 × 106/kg (n = 16) or of 8 × 106/kg (n = 15) as first-line treatment for grade II-IV aGVHD [152]. A second infusion of MSCs at the same dose was done 3 days following the first MSC infusion. (B) Percentage of responses to MSC infusion (27 patients received 1 infusion, 22 received 2 infusions, and 6 received ≥3 infusions of a median dose of 1.4 [range: 0.4-9] × 106 MSCs/kg) in adults or children with steroid refractory aGVHD reported by Le Blanc et al. (EBMT survey) [151]. (C) Complete response rate according to the organ affected in 59 pediatric patients with steroid-refractory aGVHD treated with MSCs (produced by Prochymal®; 8 infusions of 2 × 106 MSC/kg over 4 weeks followed by an additional 4 infusions administered weekly after day 28 in patients who had a partial response) (this study has been reported only in an abstract form [176] thus far). (D) Overall complete or partial response rates in patients with steroid-refractory grade II-IV aGVHD treated by second-line therapy with added MSCs (produced by Prochymal®; 8 infusions of 2 × 106 MSC/kg over 4 weeks followed by an additional 4 infusions administered weekly after day 28 in patients who had a partial response) or placebo (this study has been reported only in an abstract form [178] thus far). Biology of Blood and Marrow Transplantation 2012 18, 822-840DOI: (10.1016/j.bbmt.2011.09.003) Copyright © 2012 American Society for Blood and Marrow Transplantation Terms and Conditions