Composition and method for treating graft-versus-host disease

Abstract

Compositions and methods are provided for prevention and clinical treatment of various forms of graft-versus-host disease (GVHD) by using inhibitors of adenosine deaminase (ADA). In particular, various formulations and dosing regimens of ADA inhibitors such as pentostatin are provided for the treatment of all forms of GVHD, especially steroid-refractory acute and chronic GVHD.

1 - 38 . (canceled)  
   
   
       39 . A method for ex vivo treatment of a tissue or organ transplant having T-lymphocyte activity comprising contacting the tissue or organ transplant with a composition comprising an effective, T-lymphocytes-inhibiting amount of an adenosine deaminase.  
   
   
       40 . The method of  claim 39 , wherein the tissue or organ transplant is selected from the group consisting of stem cells, bone marrow, heart, liver, kidney, lung pancreas, small intestine, cornea and skin.  
   
   
       41 . The method of  claim 39 , wherein the adenosine deaminase inhibitor is selected from the group consisting of pentostatin, fludarabine monophosphate and cladribine.  
   
   
       42 . The method of  claim 39 , further comprising inhibiting the activity of T-lymphocytes in the tissue or organ transplant by at least about 50%.  
   
   
       43 . The method of  claim 39 , further comprising inhibiting the activity of T-lymphocytes in the tissue or organ transplant by at least about 80%.  
   
   
       44 . The method of  claim 39 , further comprising inhibiting the activity of T-lymphocytes in the tissue or organ transplant by at least about 90%.  
   
   
       45 . The method of  claim 39 , wherein contacting the tissue or organ transplant includes storing the tissue or organ transplant in a preservation solution containing pentostatin.  
   
   
       46 . The method of  claim 45 , wherein the preservation solution is one of or a mixture of Plegisol, University of Wisconsin solution, Stanford solution, and Modified Collins Solution.  
   
   
       47 . The method of  claim 39 , further comprising washing the tissue or organ transplant with a buffer containing pentostatin prior to transplantation.  
   
   
       48 . The method of  claim 47 , wherein the tissue or organ transplant is an isolated heart transplant.  
   
   
       49 . The method of  claim 48 , wherein washing the isolated heart transplant includes flush perfusing the heart with the buffer, and wherein the buffer comprises about 0.1-10 μM pentostatin.  
   
   
       50 . A method for reducing T-lymphocyte activity in a tissue or organ transplant having such activity comprising: 
 contacting, ex vivo, the tissue or organ transplant with a composition comprising an effective, T-lymphocytes-activity-reducing amount of an adenosine deaminase selected from the group consisting of pentostatin, fludarabine monophosphate and cladribine.    
   
   
       51 . The method of  claim 50 , wherein the tissue or organ transplant is selected from the group consisting of stem cells, bone marrow, heart, liver, kidney, lung pancreas, small intestine, cornea and skin.  
   
   
       52 . The method of  claim 50 , further comprising reducing the activity of T-lymphocytes in the tissue or organ transplant by at least about 50%.  
   
   
       53 . The method of  claim 50 , further comprising reducing the activity of T-lymphocytes in the tissue or organ transplant by at least about 80%.  
   
   
       54 . The method of  claim 50 , further comprising reducing the activity of T-lymphocytes in the tissue or organ transplant by at least about 90%.  
   
   
       55 . The method of  claim 50 , wherein contacting the tissue or organ transplant includes storing the tissue or organ transplant in a preservation solution containing pentostatin.  
   
   
       56 . The method of  claim 55 , wherein the preservation solution is selected from the group consisting of Plegisol, University of Wisconsin solution, Stanford solution, and Modified Collins Solution.  
   
   
       57 . The method of  claim 50 , further comprising washing the tissue or organ transplant with a buffer containing pentostatin prior to transplantation.  
   
   
       58 . The method of  claim 57 , wherein the tissue or organ transplant is an isolated heart transplant.  
   
   
       59 . The method of  claim 58 , wherein washing the isolated heart transplant includes flush perfusing the heart with the buffer, and wherein the buffer comprises about 0.1-10 μM pentostatin.  
   
   
       60 . A method for preventing increased T-lymphocyte activity in a tissue or organ transplant having such activity comprising: 
 contacting, ex vivo, the tissue or organ transplant with a composition comprising an effective amount of an adenosine deaminase selected from the group consisting of pentostatin, fludarabine monophosphate and cladribine.    
   
   
       61 . The method of  claim 60 , wherein the tissue or organ transplant is selected from the group consisting of stem cells, bone marrow, heart, liver, kidney, lung pancreas, small intestine, cornea and skin.