Graft-versus-host disease prevention

Sayer HG, Longton G, Bowden R, et al. Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. Blood 1994 84 1328-1332. 

In a study of graft-versus-host disease prevention strategies in patients after bone marrow transplantation for aplastic anemia, a significantly higher proportion of alem-tuzumab-treated patients developed cytomegalovirus reactivation compared with control patients [139 ]. Prophylaxis with aciclovir has been recommended [143 ]. Asymptomatic laboratory positive cytomegalovirus viremia should not necessarily be considered a serious infection requiring interruption of therapy. 

Graft-versus-host disease (GVHD) is caused by the activation of donor lymphocytes leading to immune damage to the skin, gut, and fiver in the recipient. An immunosuppressive regimen is administered to prevent GVHD in recipients... 

Przepiorka D, Petropoulos D, Mullen C et al. Tacrolismus for prevention of graft-versus-host-disease after mismatched unrelated donor cord blood transplantation. Bone Marrow Transplantation 1999 23 1291-1295... 

Laurent, G., D. Maraninchi, E. Gluckman, J.P Vernant, J.M. Derocq, M.H. Gaspard, B. Rio, M. Michalet, J. Reiffers, F. Dreyfus, et al.. Donor bone marrow treatment with TlOl Fab fragment-ricin A-chain immunotoxin prevents graft-versus-host disease. Bone Marrow Transplant, 1989. 4(4) 367-71. 

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. 

Zeiser R, Marks R, Bertz H, Finke J. Immunopatho-genesis of acute graft-versus-host disease implications for novel preventive and therapeutic strategies. Ann Hematol. 2004 83 551-565. 

Dai (6) prepared triptolide derivatives, (V), which were effective in treating or preventing transplantation rejection including graft-versus-host disease. 

Uses. Ciclosporin is used to prevent and treat rejection of organ transplants (kidney, liver, heart-lung) and bone marrow transplants. It may be given orally or i.v. In the context of transplantation, administration continues indefinitely and must be carefully monitored, including measurement of plasma concentration and renal function. It is generally stopped after 6 months in patients who have received a bone marrow transplant unless there is ongoing chronic graft-versus-host disease. 

Antin JH, Weisdorf D, Neuberg D, Nicklow R, Clouthier S, Lee SJ, Alyea E, McGarigle C, Blazar BR, Sonis S, Soiffer RJ, Ferrara JL. Interleukin-1 blockade does not prevent acute graft-versus-host disease results of a randomized, double-bhnd, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood 2002 100(10) 3479-82. 

Intravenous immunoglobulin administered to allogeneic bone marrow transplant recipients modifies graft-versus-host disease and prevents interstitial pneumonia and infections (14). 

Winston DJ, Antin JH, Wolff SN, Bierer BE, Small T, Miller KB, Linker C, Kaizer H, Lazarus HM, Petersen FB, Cowan MJ, Ho WG, Wingard JR, Schiller GJ, Territo MC, Jiao J, Petrarca MA, Tonetta SA. A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001 28(2) 187-96. 

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. 

Cyclodextrin complexation (See Chapter 40) can also represent a way to improve the stability and the solubility of sensitive drugs such as thalidomide. Thalidomide is currently in clinical use for the treatment and prevention of graft-versus-host disease in leukemia patients after bone marrow transplant. However, this drug is sparingly soluble in aqueous solutions (50 Kig/mL) and is readily hydrolyzed. Complexation with hydroxypropyl (3-cyclodextrin increases the solubility to 1700 Kig/mL and extends the half-life of a dilute solution from 2.1 to 4.1 h. Other vulnerable and sparingly soluble drugs stabilized by means of cyclodextrin complexation are the non-steroidal antiinflammatory drugs diclofenac, piroxicam, and indomethacin and the anthra-cycline antibiotic daunorubicin. ... 

A retrospective analysis reviewing the ontcomes of patients who nnderwent ahogeneic HSCT for severe aplastic anemia between 1978 and 1991 showed an 89% response rate (inclnding complete and partial responses). The 15-year survival rate for complete and partial responders to HSCT was 75% and 64%, respectively. Improvement in supportive care, prevention of graft-versus-host disease, and improved engraftment have further enhanced survival benefits. Considerations in deciding to treat patients with HSCT are the availability of a donor, the age of the patient, the absolute neutrophil count, and the number of transfusions received prior to transplantation. ... 

Soiffer RJ. T-cell depletion to prevent graft-versus-host disease. In Blume KG, Forman SJ, Appelbaum FR, eds. Thomas Hematopoietic Cell Transplantation, 3rd ed. Malden, MA, Blackwell Science, 2004 221-233. 

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