Graft-versus-host disease stem cells

Solomon, S.R., Mielke, S., Savani, B.N., Montero, A., Wisch, L., Childs, R., Hensel, N., Schindler, J., Ghetie, V., Leitman, S.F., Mai, T., Carter, C.S., Kurlandcr, R., Read, E.J., Vitetta, E.S., and Barrett, A.J. (2005) Selective depletion of alloreactive donor lymphocytes A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood 106,1123-1129. 

Remberger M, Ringden 0, Blau IW et al. No difference in graft-versus-host disease, relapse, and survival comparing peripheral stem cells to bone marrow using unrelated donors. Blood. 2001 98 1739-1745. 

Toxicities of the PSIs can include profound myelosuppression (especially thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache. Because nephrotoxicity is of major concern when administering calcineurin inhibitors, there is interest in increased early use of PSIs since renal toxicity is less common with these agents. However, increased use in stem cell transplantation regimens as graft-versus-host disease prophylaxis, particularly when combined with tacrolimus, has revealed an increased incidence of hemolytic-uremic syndrome. 

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. 

Le Blanc, K., Rasmusson, I., Sundberg, B., et al. (2004), Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells, Lancet, 1, 363(9419), 1439-1441. 

Ringden, O., Uzunel, M., Rasmusson, I., et al. (2006), Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease, Transplantation, 81(10), 1390-1397. 

Volume III, Pharmacology and Therapy, addresses developments in basic science, translational and clinical research that are underway to bring stem cell research to therapy, particularly for the treatment of Batten s diseases, graft-versus-host disease and adenosine deaminase deficiency. This volume covers the importance of stem cell research for the understanding of drug activities and design. It also addresses the ethical issues and constraints involved in stem cell research, and its commercial applications. 

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneichematopoietic stem cell transplantation Ho,... 

Ferrara JLM, Cooke KR, Pan L, Krenger W. 1996. The immunopathophysiology of acute graft-versus-host-disease. Stem cells. 14 473—489. 

Differential diagnosis of graft-versus-host disease currently depends on organ biopsy to distinguish it from other common complications associated with transplantation. As a means of avoiding repeated biopsies, one group analyzed the urine of patients after hematopoietic stem cell transplantation... 

Compared with stem cells purified from bone marrow, there is no risk to donors in giving cord blood. The risk of graft-versus-host disease in recipients is lower, and the ability to reconstitute hemopoiesis and immunity after transplant is improved (35,134). 

In a 23-year-old man with severe aplastic anemia, graft-versus-host disease, characterized by localized erythematous plaques and papules, developed 10 months after transplantation of unrelated cord blood stem cells, but required no therapy (35). Microsatellite DNA fingerprinting indicated a stable and persistent donor-recipient mixed chimerism, whilst the circulating erythrocytes remained of host origin. 

Of 40 patients who had achieved engraftment after allogeneic hemopoietic stem cell transplantation, 23 of whom had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease, 19 had pre-emptive therapy with ganciclovir in an initial dose of 5 mg/kg/day (4). There were no significant adverse effects attributed... 

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. 

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