Cyclosporine bone marrow transplantation

The first human kidney and bone marrow transplants using cyclosporine were reported in 1978. Oral or intravenous cyclosporine is an immunosuppressant for transplantation of these and other organs and investigations are underway for its possible use in a variety of autoimmune diseases including rheumatoid arthritis, severe psoriasis, and Crohn s disease. Dose-dependent nephrotoxicity (261—264) remains the primary limitation of the dmg and necessitates close monitoring of patients, including measurement of dmg levels in blood. Cyclosporine research has been reviewed (265—274). 

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

A 45-year-old female has a bone marrow transplant for treatment of ovarian cancer Cyclosporine is given as an immunosuppressant What is the mechanism of action of cyclosporine ... 

Kosugi, A., Sharrow, S.O., and Shearer, G.M., Effect of cyclosporin A on lymphopoiesis. I. Absence of mature T cells in thymus and periphery of bone marrow transplanted mice treated with cyclosporin A. J. Immunol., 142, 3026, 1989. 

Tacrolimus is used in situations where cyclosporine has been shown to be ineffective or cannot be used because of toxicity or otherwise. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants and in vitiligo. 

The drugs like azathioprine and cyclosporine A are used chiefly to prevent transplant rejection and in the treatment of autoimmune diseases. They are used to prevent graft rejection after kidney, liver, lung, pancreas transplant or bone marrow transplantation. 

In the management of transplants, ALG and monoclonal antibodies can be used in the induction of immunosuppression, in the treatment of initial rejection, and in the treatment of steroid-resistant rejection. There has been some success in the use of ALG and ATG plus cyclosporine to prepare recipients for bone marrow transplantation. In this procedure, the recipient is treated with ALG or ATG in large doses for 7-10 days prior to transplantation of bone marrow cells from the donor. Residual ALG appears to destroy the T cells in the donor marrow graft, and the probability of severe graft-versus-host syndrome is reduced. 

J. Nemunaitis, H. J. Deeg, and G. C. Yee, High cyclosporin levels after bone marrow transplantation associated with hypertriglyceridemia, Lancet 2 744-745 (1986). 

It is important to point out that cyclosporine is not cytotoxic in the ordinary sense and hence does not depress bone marrow. Because it does not encourage (in fact, it suppresses) graft-versus-host immune reactions, it is especially useful in bone marrow transplants. 

Gopal AK, Thorning DR, Back AL. Fatal outcome due to cyclosporine neurotoxicity with associated pathological findings. Bone Marrow Transplant 1999 23(2) 191-3. 

Koide T, Yamada M, Takahashi T, Igarashi S, Masuko M, Furukawa T, Kuroha T, Koike T, Sato M, Tanaka R, Tsuji S, Takahashi H. Cyclosporine A-associated fatal central nervous system angiopathy in a bone marrow transplant recipient an autopsy case. Acta Neuropathol (Berl) 2000 99(6) 680. ... 

Shbarou RM, Chao NJ, Morgenlander JC. Cyclosporin A-related cerebral vasculopathy. Bone Marrow Transplant 2000 26(7) 801. ... 

Avery R, Jabs DA, Wingard JR, Vogelsang G, Saral R, Santos G. Optic disc edema after bone marrow transplantation. Possible role of cyclosporine toxicity. Ophthalmology 1991 98(8) 1294-301. 

Turhal NS. Cyclosporin A and imipenem associated seizure activity in allogeneic bone marrow transplantation patients. J Chemother 1999 11(5) 410-13. 

Lindholm A, Rmgden O, Loimqvist B. The role of cyclosporine dosage and plasma levels in efficacy and toxicity m bone marrow transplant recipients. Transplantation 1987 43(5) 680-4. 

Horn TD, Altomonte V, Vogelsang G, Kennedy MJ. Erythroderma after autologous bone marrow transplantation modified by administration of cyclosporine and interferon gamma for breast cancer. J Am Acad Dermatol 1996 34(3) 413-17. 

Mori A, Tanaka J, Kobayashi S, Hashino S, Yamamoto Y, Ota S, Asaka M, Imamura M. Fatal cerebral hemorrhage associated with cyclosporin-A/FK506-related encephalopathy after allogeneic bone marrow transplantation. Ann Hematol 2000 79(10) 588-92. 

Kruger HU, Schuler U, Proksch B, Gobel M, Ehninger G. Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients. Antimicrobial agents and chemotherapy. 1990 Jun 34(6) l 048-52. 

Dieterle A, Gratwohl A, Nizze FI, Fluser B, Mihatsch MJ, Thiel G, Tichelli A, Signer E, Nissen C, Speck B. Chronic cyclosporine-associated nephrotoxicity in bone marrow transplant patients. Transplantation 1990 49 1093-1100. 

Takamatsu Y+, Bone Marrow Transplant 28(4), 421 (with cyclosporine)... 

Immunosuppressants are drugs capable of suppressing immune responses. They are used to treat autoimmune disease, aUergy, multiple myeloma, and chronic nephritis, and in organ transplantation. For example, immunosuppressants that are used to provide maintenance immunosuppression in solid organ and bone marrow transplant patients include cyclosporine, everoHmus (Ever), mycophe-nolic acid (MPA), Siro, and Tac (Figure 33-13). 

Cyclosporine, proprietary names Sandimmune (cyclosporine) and Neoral, is a cyclic peptide composed of 11 amino acids, some of novel structure, isolated from the fungus Trichoderma polysporum (Figure 33-13). The compound has been shown effective in suppressing acute rejection in recipients of allograft organ transplants. Cyclosporine is approved for use in renal, cardiac, hepatic, pancreatic, and bone marrow transplants. 

Joseph Murray in Boston performed the first successful transplant in 1954 when he performed a donor transplant from one twin to the other. In 1959 Dameshek and Schwartz used 6-mercaptopurine (6-MP) in place of irradiation to precondition patients for bone marrow transplantation. Caine developed this work with the introduction of a safer derivative of 6-MP called azathioprine (AZA). By 1963, maintenance AZA and corticosteroids became the standard regimen for kidney transplantation. Kidney transplant or graft survival with these treatment protocols was approximately 40% at 12 months. In the late 1970s to early 1980s cyclosporin A (Cy A) was introduced and has been the mainstay immunosuppressive regimen in combination with AZA and corticosteroids. Cy A-based protocols led to fewer episodes of acute rejection and improved graft survival at 12... 

Ruutu T, Volin L, Parkkli T, et al. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor A prospective randomized study. Blood 2000 96 2391-2398. 

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