Cell transplantation prevention

Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep 2000 49 1-125, CE1-7. 

Cyclosporin-A In 1972, the immunosuppressive effect of cyclosporin-A, an antibiotic secreted by some fungi, was discovered. Other antibiotics also have immunosuppressive effects. They interfere with proliferation of T-helper cells by preventing the entry of a transcription factor into the nucleus. This prevents transcription of the genes involved in the proliferative process. Their use is restricted to patients after transplantation, since there are serious side-effects, for example, toxic effects on the mbules of the kidney. This precludes their use for treatment of non-life-threatening autoimmune diseases. 

Targeting of anti-inflammatory and anti-fibrotic drugs to the proximal tubular cell may prevent tubulointerstitial inflammation and scarring secondary to systemic and glomerular infection and proteinuria. Furthermore, tubular drug dehvery may be beneficial during shock, renal transplantation, ureter obstruction, diabetes, proteinuria, renal carcinoma and some tubular defect diseases such as Fanconi and Bartter s s5mdrome. 

Muromonab is a mouse monoclonal antibody against the CD3 receptor of T-lymphocytes. Its activity is based on inhibition of interactions between antigen-presenting cells and T-cells. By preventing antigen presentation it suppresses T-cell activation and proliferation. The indication for muromonab is the treatment of acute graft rejection after kidney, liver and hart transplantations. Its adverse effects consist of those symptoms that are initiated by the release of cytokines and lymphokines as a result of the reaction of muromonab with CD3 positive T-lymphocytes. These symptoms may vary from a mild flu-like syndrome to serious cardiac, pulmonale and neurological reactions. 

Because of these immunosuppressant activities, hydroxychloroquine is used to treat some autoimmune disorders, eg, rheumatoid arthritis and systemic lupus erythematosus. It has also been used to both treat and prevent graft-versus-host disease after allogeneic stem cell transplantation. 

Pentostatin is an adenosine deaminase inhibitor primarily used as an antineoplastic agent for lymphoid malignancies, and produces a profound lymphopenia. It is now frequently used for steroid-resistant graft-versus-host disease after allogeneic stem cell transplantation, as well as in preparative regimens prior to those transplants to provide severe immunosuppression to prevent allograft rejection. 

Which gene or genes will be most effective in preventing and/or delaying islet cell transplant rejection ... 

Bind RK, Cohen BA, Russell E, Spero K, Joshi A, Oyama Y, Karpus WJ, Fuo K, Jovauic B, Traynor A, Karth K, Stefaski D, Bums WH (2003a) Haematopoietic stem cell transplantation for progressive multiple sclerosis failure of intense immune suppression to prevent disease progiession m patients with high disability scores. Blood 102 2373-2378. 

Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD. Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant. Blood 1991 78(l) 246-50. 

Severe fluid retention resistant to furosemide and fluid restriction was observed in 10 patients randomized to receive subcutaneous oprelvekin 50 pg/kg/day to prevent mucositis and acute graft-versus-host disease after allogeneic stem cell transplantation (2). One patient also had a large but reversible increase in serum transaminases. 

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. 

Sullivan KM, Dykewicz CA, Longworth DL, et al. Preventing opportunistic infections after hematopoietic stem cell transplantation The Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation practice guidelines and beyond. Hematology (Am Soc Hematol Educ Program) 2001 392 21. 

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