Stem cells GvHD

FDA grants Fast Track status to Osiris s GvHD stem cell therapy Osiris Therapeutics, Inc. PRESS RELEASE 2005 January 31. 

Of 1000 allogeneic stem cell transplantations, 25 patients developed grade IV acute GVHD. The patient reported in this study is the only patient with such severe disease who, one year after the therapy, was living a normal life at home. The other 24 patients died a median of 2 months after transplantation. This case supports MSC therapy for prophylaxis and treatment of GVHD. 

Antin JH, Lee SJ, Neuberg D, Alyea E, Soiffer RJ, Sonis S, Ferrara JL. A phase Fll double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation. Bone Marrow Transplant 2002 29(5) 373-7. 

IL-12 is also a critical cytokine regulating NK and T-ceH function, and it has been suggested that reduced expression and production of IL-12 from activated umbilical cord blood may contribute to the immaturity in its cellular immunity and may explain decreased GVHD following umbilical cord blood stem-cell transplantation. ... 

There are three types of stem cells embryonic stem cells, cord blood stem cells, and adult stem cells [99 ]. Ideally, these cells should be from an HLA-matched sibling. However, a significant number of patients lack an appropriate HLA-matched donor. For these patients there is a choice between a T-cell-depleted mismatched related donor transplant or an unrelated donor stem cell transplant with the risk of graft-versus-host disease (GVHD) [loo ll. 

Cord blood is used as an alternative source of hemopoietic stem cells, with the potential advantage that it has less-stringent requirements for HLA matching than hematopoietic stem cells from an adult unrelated donor. Because the neonatal immune system is naive, transplantation of cord blood stem cells yields a lower incidence of acute and chronic GVHD [99 100 =,101 =,102 =,103, 104 ]. The low expression of co-stimulatory molecules on cord blood stem cells could contribute to the lower risk of rejection by the immune system compared with bone marrow transplantation [99 ]. A potential disadvantage of cord blood stem cells is that immune reconstitution is substantially delayed compared with bone marrow transplantation, making recipients more susceptible to... 

In a Spanish study the incidence of GVHD was low with co-infusion of mobilized hemopoietic stem cells as support for single-unit unrelated cord blood transplantation. However, GVHD occurred more often in patients who received unrelated cord blood transplants (63%) compared with patients who received transplants from related HLA-matched-identical donors (33%) [102. ... 

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