Abstract
Introduction: This study examines whether malignant disease under treatment influences the incidence of cyclosporine or FK-506 neurotoxicity after myeloablative conditioning and allogeneic bone marrow transplantation (allo-BMT).
Methods: Review of 290 patients who received myeloablative conditioning prior to allo-BMT and cyclosporine/FK-506 identified 21 (7.2%) patients with neurotoxicity confirmed by computed tomography or magnetic resonance. Underlying malignancy necessitating allo-BMT included leukemias (67%), lymphoma (10%), myelodysplastic syndrome (10%), and multiple myeloma (MM). Frequency of neurotoxicity by disease was compared.
Results: The highest incidence of neurotoxicity was present with MM (25%), whereas the lowest incidence was present with lymphoma (2.7%). Other diseases demonstrated intermediate incidence, including acute leukemias (10%), myelodysplastic syndrome (6.4%), and chronic myelogenous leukemia (4.9%).
Conclusion: Cyclosporine/FK-506 neurotoxicity varied according to the underlying malignancy. The variable susceptibility to the development of neurotoxicity in this population may depend on the interaction of host vasculature with disease specific factors. Understanding the cause of neurotoxicity could improve survival after allo-BMT.
Similar content being viewed by others
References
Clift RA, Buckner CD, Appelbaum FR, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 1990;76:1867–1871.
Mehta J, Tricot G, Jagannath S, et al. Salvage autologous or allogeneic transplantation for multiple myeloma refractory to or relapsing after a first-line autograft? Bone Marrow Transplant 1998;21:887–892.
Bensinger W I, Buckner CD, Anasetti C, et al. Allogeneic marrow transplantation for multiple myeloma: An analysis of risk factors on outcome. Blood 1996;88:2787–2793.
Barlogie B, Jagannath S, Desikan KR, et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999;93:55–65.
Kulkarni S, Powles RL, Treleaven JG, et al. Impact of previous high dose therapy on outcome after allografting for multiple myeloma. Bone Marrow Transplant 1999;23:675–680.
Anderson JE, Litzow MR, Appelbaum FR, et al. Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin’s disease: the 21-year Seattle experience. J Clin Oncol 1993;11:2342–2350.
Chopra R, Goldstone AH, Pearce R, et al. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin’s lymphoma: a case-controlled analysis of the European bone marrow transplant group registry data. J Clin Oncol 1992;10:1690–1695.
Dann EJ, Daugherty CK, Larson RA. Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin’s disease and non-Hodgkin’s lymphoma. Bone Marrow Transplant 1997;20:369–374.
Ratanatharathorn V, Uberti J, Karanes C, et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin’s lymphoma. Blood 1994;84:1050–1055.
Schots R, Kaufman L, Van Riet I, et al. Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation. Leukemia 2003;17:1150–1156.
Schots R, Van Riet I, Ben Othman T, et al. An early increase in serum levels of C-reactive protein is an independent risk factor for the occurrence of major transplant complications and 100 day transplant related mortality after allogeneic bone marrow transplantation. Bone Marrow Transplant 2002;30:441–446.
Joss DV, Barrett AJ, Kendra JR, et al. Hypertension and convulsions in children receiving cyclosporin A. Lancet 1982.i:906.
Boogaerts MA, Zachee P, Verwilghen RL. Cyclosporin, methylprednisolone, and convulsions. Lancet 1982;ii:1216, 1217.
Dieperink H, Moller J. Ketoconazole and cyclosporin. Lancet 1982;ii:1217.
Durrant S, Chipping PM, Palmer S, Gordon-Smith EC. Cyclosporin A, methylprednisolone, and convulsions. (letter). Lancet 1982;829,830.
Noll RB, Kulkarni R. Complex visual hallucinations and cyclosporine. Arch Neurol 1984;41:329,330.
Shah D, Rylance PB, Rogerson ME, et al. Generalized epileptic fits in renal transplant recipients given cyclosporin A. Br Med J 1984;289:1347,1348.
Atkinson K, Biggs J, Phil D, et al. Cyclosporine-associated central-nervous-system toxicity after allogeneic bone-marrow transplantation. N Engl J Med 1984;38:527.
Kahan BD, Wideman CA, Flechner S, et al. Anaphylactic reaction to intravenous cyclosporin. (letter) Lancet 1984;i:52.
Thompson CB, Sullivan KM, June CH, Thomas ED. Association between cyclosporin neurotoxicity and hypomagnesemia. Lancet 1984;ii:1116–1120.
Powell-Jackson PR, Carmichael FJL, Calne RY, Williams R. Adult respiratory distress syndrome and convulsions associated with administration of cyclosporine in liver transplant recipients. Transplantation 1984;38:341–343.
Wilczek H, Ringden O, Tyden G. Cyclosporine-associated central nervous system toxicity after renal transplantation. Transplantation 1984;39:110.
Atkinson K, Biggs J, Darveniza P, Boland J, Concannon A, Dodds A. Cyclosporine-associated central nervous system toxicity after allogeneic bone marrow transplantation. Transplantation 1984;38:34–37.
Sloane JP, Lwin KY, Gore ME, Powles RL, Smith JF. Disturbance of blood-brain barrier after bone-marrow transplantation. Lancet 1985;ii:280,281.
Velu T, Debusscher L, Stryckmans PA. Cyclosporin-associated fatal convulsions. (letter) Lancet 1985;i:219.
Beaman M, Parvin S, Veitch PS, Walls J. Convulsions associated with cyclosporin A in renal transplant recipients. Br Med J 1985;290:139,140.
Berden JHM, Hoitsma AJ, Merx JL, Keyser A. Severe central-nervous-system toxicity associated with cyclosporin. Lancet 1985;i:219,220.
Rubin AM, Kang H. Cerebral blindness and encephalopathy with cyclosporin A toxicity. Neurology 1987;37:1072–1076.
de Groen PC, Aksamit AJ, Rakela J, Forbes GS, Krom RAF. Central nervous system toxicity after liver transplantation: the role of cyclosporin and cholesterol. N Engl J Med 1987;317:861–866.
Bhatt BD, Meriano FV, Buchwald D. Cyclosporine-associated central nervous system toxicity. N Engl J Med 1988;318:788, 789.
Hoefnagels WAJ, Gerritsen EJA, Brouwer OF, Souverijn JHM. Cyclosporin encephalopathy associated with fat embolism induced by the drug’s solvent. Lancet 1988;II:901.
Wilson SE, de Groen PC, Aksamit AJ, et al. Cyclosporin A-induced reversible cortical blindness. J Clin Neuroophthalmol 1988; 8:215–220.
Lane RJM, Roche SW, Leung AAW, Greco A, Lange LS. Cyclosporin neurotoxicity in cardiac transplant recipients. J Neurol Neurosurg Psychiatry 1988;51:1434–1437.
Scheinman SJ, Reinitz ER, Petro G, et al. Cyclosporine central neurotoxicity following renal transplantation: report of a case using magnetic resonance images. Transplantation 1990;49(1):215,216.
Lucey MR, Kolars JC, Merion RM, et al. Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA. Lancet 1990;335:11–15.
Ghalie R, Fitzsimmons WE, Bennett D, Kaizer H. Cortical blindness: a rare complication of cyclosporine therapy. Bone Marrow Transplant 1990;6:147–149.
Lloveras JJ, Larrue V, Suc E, et al. Leukoencephalopathy after cyclosporine in a liver transplant. Clin Transplantation 1990;4:58–62.
Reece DE, Frei-Lahr DA, Shepherd JD, et al. Neurologic complications in allogeneic bone marrow transplant patients receiving cyclosporin. Bone Marrow Transplant 1991;8:393–401.
Truwit CL, Denaro CP, Lake JR, DeMarco T. MR imaging of reversible cyclosporin A-induced neurotoxicity. AJNR 1991;12:651–659.
Nussbaum ES, Maxwell RE, Bitterman PB, et al. Cyclosporine A toxicity presenting with acute cerebellar edema and brainstem compression. J Neurosurg 1995;82:1068–1070.
Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. Am J Roentgenol 1995;165:627–631.
Bartynski WS, Grabb BC, Zeigler Z, Lin L, Andrews DF. Watershed imaging features of clinical vascular injury in cyclosporin A neurotoxicity. J Comput Assist Tomogr 1997;21(6):872–880.
Jansen O, Krieger D, Krieger S, Sartor K. Cortical hyperintensity on proton density—Weighted images: an MR sign of cyclosporine-related encephalopathy. AJNR 1996;17:337–344.
Zimmer WE, Hourihane JM, Wang HZ, Schriber JR. The effect of human leukocyte antigen disparity on cyclosporin neurotoxicity after allogeneic bone marrow transplantation. AJNR 1998;19:601–608.
Zoja C, Furci L, Ghilardi F, et al. Cyclosporin-induced endothelial cell injury. Lab Invest 1986;55:455–462.
Wijdicks EFM. Neurologic manifestations of immunosuppressive agents. In: Wijdicks EFM, ed. Neurologic Complications in Organ Transplant Recipients. Boston, MA: Butterworth-Heinemann, 1999, pp. 127–140.
Holler E, Kolb HJ, Hiller E, et al. Microangiopathy in patients on Cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation. Blood 1989;73:2018–2024.
Scherrer U, Vissing SF, Morgan BJ, et al. Cyclosporine-induced sympathetic activation and hypertension after heart transplantation. N Engl J Med 1990;323:693–699.
Mark AL. Editorial: cyclosporine, sympathetic activity, and hypertension. N Engl J Med 1990;323:748–750.
Hinchey J, Chaves C, Appignani B, et al. A Reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494–500.
Provenzale JM, Petrella JR, Cruz LC, et al. Quantitative assessment of diffusion abnormalities in posterior reversible encephalopathy syndrome. AJNR 2001;22:1455–1461.
Mukherjee P, McKinstry RC. Reversible posterior leukoencephalopathy syndrome: evaluation with diffusion-tensor MR imaging. Radiology 2001;219:756–765.
Covarrubias DJ, Leutmer PH, Campeau NG. Posterior reversible encephalopathy syndrome:prognostic utility of quantitative diffusion-weighted MR images. AJNR 2002;23:1038–1048.
Bartynski WS, Zeigler Z, Spearman MP, Lin L, Shadduck RK, Lister J. Etiology of Cortical and White Matter lesions in Cyclosporin-A and FK-506 neurotoxicity. AJNR 2001;22:1901–1914.
Bartynski WS, Zeigler ZR, Shadduck RK, Lister J. Pretransplantation conditioning influence on the incidence of cyclosporine and FK-506 neurotoxicity in allogeneic bone marrow transplantation. AJNR 2004;25:261–269.
Fung JJ, Todo S, Tzakis A et al. Current status of FK 506 in liver transplantation. Transplant Proc 1991;23:1902–1908.
Ay H, Buonanno FS, Schaefer PW, et al. Posterior leukoencephalopathy without severe hypertension, utility of diffusion weighted MRI. Neurology 1998;51:1369–1376.
Ito Y, Arahata Y, Goto Y, et al. Cisplatin neurotoxicity presenting as Reversible posterior leukoencephalopathy syndrome. AJNR 1998;19:415–417.
Zeigler ZR, Shadduck RK, Nemunaitis J, Andrews DF, Rosenfeld CS. Bone marrow transplant-associated thrombotic microangiopathy: a case series. Bone Marrow Transplant 1995;15:247–253.
Silva VA, Frei-Lahr D, Brown RA, Herzig GP. Plasma exchange and vincristine in the treatment of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura associated with bone marrow transplantation. J Clin Apheresis 1991;6:16–20.
Carlson K, Smedmeyr B, Hagberg H, Oberg G, Simonsson B. Haemolytic uraemic syndrome and renal dysfunction following BEAC (BCNU, etoposide, Ara C, cyclophosphamide) ± TBI and auto-BMT for malignant lymphomas. Bone Marrow Transplant 1993;11:205–208.
Thomas ED, Storb R, Clift RA, et al. Bone marrow transplantation. N Engl J Med 1975;292:823–902.
Jones RJ, Lee KSK, Beschorner WE, et al. Veno-occlusive disease of the liver following bone marrow transplantation. Transplantation 1987;44:778.
Holler E, Kolb HJ, Moller A, et al. Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation. Blood 1990;75:1011–1016.
Remberger M, Ringden O, Marking L. TNFα levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant 1995;15:99–104.
Hill, GR, Crawford JM, Cooke KR, et al. Total body irradiation and acute graft-versus-host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood 1997;90:3204–3213.
Huang XJ, Wan J, Lu DP. Serum TNFα levels in patients with acute graft-versus-host disease after bone marrow transplantation. Leukemia 2001;15:1089–1091.
Miralbell R, Bieri S, Mermillod B, et al. Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease. J Clin Oncol 1996;14:579–585.
Juckett M, Perry EH, Daniels BS, Weisdorf DJ. Hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant 1991;7:405–409.
Rabinowe SN, Soiffer RJ, Tarbell NJ, et al. Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies. Blood 1991;77:1837–1844.
Togitani K, Takeyama K, Yokozawa T, et al. Thrombotic microangiopathy of hyperacute onset after autologous peripheral blood stem cell transplantation in malignant lymphoma. Bone Marrow Transplant 1998;21:1263–1266.
Rippe DJ, Edwards MK, Schrodt, et al. Reversible cerebral lesions associated with Tiazofurin usage: MR demonstration. J Comput Assist Tomog 1988;12:1078–1081.
Heran F, Defer G, Brugieres P, Brenot F, et al. Cortical blindness during chemotherapy: clinical, CT and MR correlations. J Comput Assist Tomog 1990;14:262–266.
Vaughn DJ, Jarvik JG, Hackney D, et al. High dose cytarabine neurotoxicity: MR findings duriung acute phase. AJNR 1993;14:1014–1016.
Nurnberger W, Michelmann I, Burdach S, Gobel U. Endothelial dysfunction after bone marrow transplantation: Increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications. Ann Hematol 1998;76:61–65.
Daly AS, Hasegawa WS, Lipton JH, Messner HA, Kiss TL. Transplantation-associated thrombotic microangiopathy is associated with transplantation from unrelated donors, acute graft-versus-host disease and venooclusive disease of the liver. Transfusion Apheresis Science 2002;27:3–12.
Daly AS, Xenocostas A, Lipton JH. Transplantation-associated thrombotic microangiopathy: twenty-two years later. Bone Marrow Transplant 2002;30:709–715.
Pham PTT, Peng A, Wilkinson AH, et al. Cyclosporine and tacrolimus-associated thrombotic microangiopathy. Am J Kidney Dis 2000;36:844–850.
Paquette RL, Tran L, Landaw EM. Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis. Bone Marrow Transplant 1998;22:351–357.
Kanamori H, Maruta A, Sasaki S, et al. Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. Bone Marrow Transplant 1998;21:705–709.
Forrest DL, Thompson K, Nevill TJ et al. Allogeneic hematopoeitic stem cell transplantation for progressive follicular lymphoma. Bone Marrow Transplant 2002;29:973–978.
Kiss TL, Panzarella T, Messner HA et al. Busulfan and cyclophosphamide as a preparative regimen for allogeneic blood and marrow transplantation in patients with non-Hodgkins lymphoma. Bone Marrow Transplant 2003;31:73–78.
Clift RA, Buckner ED, Thomas ED, et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 1994;84:2036–2043.
Clift RA, Storb R. Marrow transplantation for CML: the Seattle experience. Bone Marrow Transplant 1996;17 (Suppl 3):S1-S3.
Burt RK, Rowlings P, Santos GW. Acute myeloid leukemia. In: Burt RK, Deeg HJ, Lothian ST, Santos GW, eds. Bone Marrow Transplantation. Georgetown, TX: Landes Bioscience 1996, pp. 162–172.
Burt RK, Rowlings P, Santos GW. Acute Lymphoblastic Leukemia. In: Burt RK, Deeg HJ, Lothian ST, Santos GW, eds. Bone Marrow Transplantation. Georgetown, TX: Landes Bioscience 1996, pp. 173–187.
Antin JH, Ferrara JLM. Cytokine dysregulation and acute graft-versus-host disease. Blood 1992;80(12):2964–2968.
Ferrara JLM. Pathogenesis of acute graft-versus-host disease: Cytokines and cellular effectors. J Hematother Stem Cell Res 2000;9:299–306.
Holler E, Kolb HJ, Mittermuller J, et al. Modulation of acute graft-versus-host disease after allogeneic bone marrow transplantation by tumor necrosis factor α (TNFα) release in the course of pretransplant conditioning: Role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNFα (MAK 195F). Blood 1995;86:890–899.
Takatsuka H, Takemoto Y, Okada M, et al. Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report. Cytokine 2000;12:1225–1227.
Fujimori Y, Takatsuka H, Takemoto Y, et al. Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogenic bone marrow transplantation. Br J Haematol 2000;109:652–657.
Kayaba H, Hirokawa M, Watanabe A, et al. Serum markers of graft-versus-host disease after bone marrow transplantation. J Allergy Clin Immunol 2000;106:S40-S44.
Nakamura H, Komatsu K, Ayaki M, et al. Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-γ in patients with acutegraft-versus-host disease after allogeneic bone marrow transplantation. J Allergy Clin Immunol 2000;106:S45-S50.
Takatsuka H, Takemoto Y, Okamoto T, et al. Predicting the severity of graft-versus-host disease from interleukin-10 levels after bone marrow transplantation. Bone Marrow Transplant 1999;24:1005–1007.
Yabe M, Yabe H, Hattori K, et al. Role of interleukin-12 in the development of acute graft-versus-host disease in bone marrow transplant patients. Bone Marrow Transplant 1999;24:29–34.
Remberger M, Ringden O. Serum levels of cytokines after bone marrow transplantation: increased IL-8 levels during severe veno-occlusive disease of the liver. Eur J Haematol 1997;59:254–262.
Ballermann BJ. Endothelial cell activation. Kidney International 1998;53:1810–1826.
Mantovani A, Bussolino F, Dejana E. Cytokine regulation of endothelial cell function. FASEB J 1992;6:2591–2599.
O’Shea JJ, Frucht DM, Duckett CS. Cytokines and cytokine receptors. In Rich RR, Fleisher TA, Shearer WT, Kotzin BL, Schroeder HW eds. Clinical Immunology 2nd ed. London: Mosby, 2001, pp. 1:12.1–12.22.
Munshi NC, Tricot G, Barlogie B. Plasma cell Neoplasms. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology, 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 2465–2499.
Roodman GD. Role of the bone marrow microenvironment in multiple myeloma. J Bone Min Res 2002;17:1921–1925.
Lauta VM. Interleukin-6 and the network of several cytokines in multiple myeloma: An overview of clinical and experimental data. Cytokine 2001;16:79–86.
Kantarjian HM, Faderl S, Talpaz M. Chronic leukemias. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 2433–2465.
Kantarjian HM, Estey E. Myelodysplastic syndromes. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 2499–2509.
Strife A, Lambeck C Wisniewski D, et al. Discordant maturation as the primary biological defect in chronic myelogenous leukemia. Cancer Res 1988;48:1035–1041.
Udomsakdi C, Eaves CJ, Swolin B, et al. Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level. Proc Natl Acad Sci USA 1992;89:6192–6196.
Verfaille CM, Hurley R, Zhao RCH, et al. Pathophysiology of CML: do defects in integrin function contribute to the premature circulation and massive expansion of the BCR/ABL positive clone? J Lab Clin Med 1997;129:584–591.
Armitage JO, Mauch PM, Harris NL, Bierman P. Non-Hodgkins lymphomas. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 2256–2316.
Humar A, St. Louis P, Mazzulli T, et al. Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplantation recipients. J Infect Dis 1999;179:484–488.
Waiser J, Budde K, Rudolph B, et al. H. De Novo hemolytic uremic syndrome postrenal transplant after cytomegalovirus infection. Am J Kidney Dis 1999;34;556–560.
Zeigler ZR, Rosenfeld CS, Andrews DF, III et al. Plasma von Willebrand factor antigen (vWF:AG) and thrombomodulin (TM) levels in adult thrombotic thrombocytopenic purpura/hemolytic uremic syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). Am J Hematol 1996;53:213–220.
Honczarenko M, Campbell JJ, Silberstein LE. Chemokines and chemokine receptors. In: Rich RR, Fleisher TA, Shearer WT, Kotzin BL, Schroeder HW, eds, Clinical Immunology 2nd ed. London: Mosby, 2001, pp. 1:13.1–13.14.
Gerritsen ME, Bloor CM. Endothelial cell gene expression in response to injury. FASEB J 1993;7:523–532.
Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91:3527–3561.
Owman C, Hadrbeo JE. Functional heterogeneity of cerebrovascular endothelium. Brain Behavior Evol 1988;32:65.
Grau GE, de Moreloose P, Bulla O, et al. Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells. Thromb Haemost 1997;77:585.
Mitra D, Kim J, MacLow C, Karsan A, Laurence J. Role of caspases 1 and 3 and Bcl-2-related molecules in endothelial cell apoptosis associated with thrombotic microangioplasties. Am J Hematol 1998;59:279–287.
Abe Y, Sekiya S, Yamasita T, Sendo F. Vascular hyperpermeability induced by tumor necrosis factor and its augmentation by IL-1 and INF-γ is inhibited by a selective depletion of neutrophils with a monoclonal antibody. J Immunol 1990;145:2902–2907.
Halloran PF, Batiuk TD, Goes N, Campbell PM. Immunologic concepts. In: Stuart FP, Abeleassis MM, Kaufman DB eds. Organ Transplantation. Georgetown, TX: Landes Bioscience 2000, pp. 1–44.
Cerilli J, Brasile L, Galouzis T, Lempert N, Clarke J. The vascular endothelial cell antigen system. Transplantation 1985;39:286–289.
Graze PR, Gale RP. Chronic graft versus host disease: a syndrome of disordered immunity. Am J Med 1979;66:611–620.
Rouquette-Gally AM, Boyeldieu D, Gluckman E, et al. Autoimmunity in 28 patients after allogeneic bone marrow transplantation: comparison with Sjogren syndrome and scleroderma. Br J Hematol 1987;66:45–47.
Holmes JA, Livesey SJ, Bedwell AE, et al. Autoantibody analysis in chronic graft-versus-host disease. Bone Marrow Transplant 1989;4:529–531.
Bradley JR, Lockwood CM, Thiru S. Endothelial cell activation in patients with systemic vasculitis. QJ Med 1994;87:741–745.
Pall AA, Savage COS. Mechanisms of endothelial cell injury in vasculitis. Springer Semin Immunopathol 1994;16:23–27.
Dekker GA, Sibai BM. Etiology and pathogenesis of preeclampsia: current concepts. Am J Obstet Gynecol 1998;179:1359–1375.
Jalkanen S, Salmi M. Lymphocyte adhesion and trafficking. In: Rich RR, Fleisher TA, Shearer WT, Kotzin BL, Schroeder HW, eds. Clinical Immunology 2nd ed. London: Mosby, 2001, pp. 1:3.1–3.16.
Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science 1996;272:60–66.
Butcher EC. Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity. Cell 1991;67:1033–1036.
Sibai BM. Eclampsia: maternal outcome in 254 consecutive cases. Am J Obsete Gynecol 1990;163:1049–1055.
Hypertensive disorders of pregnancy. In: Cunningham FG, Grant NF, LeVerno KJ, Gilstrap LC, Hauth JC, Wenstrom KD, eds. Williams’ Obstetrics 21st ed. 2001, pp. 567–618.
Shweiki D, Ahuva I, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogensis. Nature 1992;359:843–845.
Levy AP, Levy NS, Wegner S, et al. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 1995;270:13,333–13,340.
Kevil CG, Payne DH, Mire E, et al. Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial tight junctional proteins. J Biol Chem 1998;273:15,099–15,103.
Schoch HJ, Silvia F, Marti HH. Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain. Brain 2002;125:2549–2557.
Chavez JC, Agani F, Pichiule, et al. Expression of hypoxia-inducible factor 1α in the brain of rats during chronic hypoxia. J Appl Physiol 2000;89:1937–1942.
Olesen SP. Rapid increase in blood-brain barrier permeability during severe hypoxia and metabolic inhibition. Brain Res 1986;368:24–29.
Teshima T, Hill GR, Pan L, et al. IL-11 separated graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation. J Clin Invest 1999;104:317–325.
Tsukada N, Kobata T, Aizawa Y, et al. Graft-versus-leukemia effect and graft-versus-host disease can be differentiated by cytotoxic mechanisms in a murine model of allogeneic bone marrow transplantation. Blood 1999;93:2738–2747.
Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75:555–562.
Ratain M. Pharmacokinetics and pharmacodynamics. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 335–345.
Hellman S. Principles of Cancer management. Radiation therapy. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer Principles & Practice of Oncology 6th ed. Philadelphia, PA: Lippincott Williams& Wilkins, 2001, pp. 265–289.
Gahrton G, Tura S, Ljungman P, et al. Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 1995;13(6):1312–1322.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bartynski, W.S., Zeigler, Z.R., Shadduck, R.K. et al. Variable incidence of cyclosporine and FK-506 neurotoxicity in hematopoeitic malignancies and marrow conditions after allogeneic bone marrow transplantation. Neurocrit Care 3, 33–45 (2005). https://doi.org/10.1385/NCC:3:1:033
Issue Date:
DOI: https://doi.org/10.1385/NCC:3:1:033