Abstract
Severe autoimmune diseases are not cured by current conventional treatments. Preclinical studies of treatments requiring stem cell transplantation have shown sustained remissions in some models of autoimmune diseases. Both autologous stem cell transplantation after high-dose immunoablative therapy and allogeneic stem cell transplantation have a profound effect on the recipient's immunological system. Pilot clinical studies of autologous stem cell transplantation are being conducted. Sustained remissions will require the induction of tolerance to autoantigens during recovery. In a group of patients highly selected to minimize transplant-related mortality, allogeneic stem cell transplantation should be tested to determine if elimination of the autoreactive immunological system will achieve sustained remissions. These are promising therapies which will require long-term follow-up of patients to evaluate efficacy.
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REFERENCES
Ikehara S, Kawamura M, Takao F, Inaba M, Yasumizu R, Than S, Hisha H, Sugiura K, Koide Y, Yoshida TO, Ida T, Imura H, Good RA: Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. Proc Natl Acad Sci USA 87:8341-8344, 1990
Ikehara S: Autoimmune diseases as stem cell disorders: Normal stem cell transplant for their treatment (Review). Int J Mol Med 1:5-16, 1998
McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD: Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med 182:75-85, 1995
Drexhage HA, Delemarre FGA, Radosevic K, Leenen PJM: Dendritic cells in autoimmunity, Dendritic Cells: Biology and Clinical Applications. Lotze MT, Thomson AW (eds). San Diego, Academic Press, 1999, pp 400-401
Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, Tsompanakou A: Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: First results of a pilot study. Bone Marrow Transplant 20:631-638, 1997
Fassas A, Sakellari I, Kimiskidis V, Anagnostopoulos A, Kapinas K, Lalayanni C, Vadikolia C, Kaloyannidis P, Kazis A: An interim analysis of autologous blood SCT as treatment of multiple sclerosis (MS), in respect to toxicity and efficacy (abstract). Bone Marrow Transplant 23(Suppl 1):S34, #104, 1999
Snowden JA, Biggs JC, Milliken ST, Fuller A, Staniforth D, Passuello F, Renwick J, Brooks PM: A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis. Bone Marrow Transplant 22:1035-1041, 1998
McSweeney PA, Furst DE, Storek J, Nash RA, Nelson JL, Wener M, Sullivan KM: High-dose immunosuppressive therapy (HDIT) using total body irradiation (TBI), cyclophosphamide (CY) and ATG with autologous CD34-selected peripheral blood stem cell (PBSC) rescue as treatment for severe systemic sclerosis (SSc) (abstract). Blood 92(Suppl 1):295a, #1208, 1998
Burt RK, Traynor AE, Pope R, Schroeder J, Cohen B, Karlin KH, Lobeck L, Goolsby C, Rowlings P, Davis FA, Stefoski D, Terry C, Keever-Taylor C, Rosen S, Vesole D, Fishman M, Brush M, Mujias S, Villa M, Burns WH: Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation. Blood 92:3505-3514, 1998
Good RA, Ikehara S: Preclinical investigations that subserve efforts to employ bone marrow transplantation for rheumatoid or autoimmune diseases. J Rheumatol 24:5-12, 1997
Knaan-Shanzer S, Houben P, Kinwel-Bohre EP, van Bekkum DW: Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation. Bone Marrow Transplant 8:333-338, 1991
van Gelder M, Kinwel-Bohre EP, van Bekkum DW: Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT. Bone Marrow Transplant 11:233-241, 1993
Karussis DM, Vourka-Karussis U, Lehmann D, Ovadia H, Mizrachi-Koll R, Ben-Nun A, Abramsky O, Slavin S: Prevention and reversal of adoptively transferred, chronic relapsing experimental autoimmune encephalomyelitis with a single high dose cytoreductive treatment followed by syngeneic bone marrow transplantation. J Clin Invest 92:765-772, 1993
van Gelder M, van Bekkum DW: Effective treatment of relapsing experimental autoimmune encephalomyelitis with pseudoautologous bone marrow transplantation. Bone Marrow Transplant 18: 1029-1034, 1996
Euler HH, Harten P, Zeuner RA, Schwab UM: Recombinant human granulocyte colony stimulating factor in patients with systemic lupus erythematosus associated neutropenia and refractory infections. J Rheumatol 24:2153-2157, 1997
Euler HH, Marmont AM, Bacigalupo A, Fastenrath S, Dreger P, Hoffknecht M, Zander AR, Schalke B, Hahn U, Haas R, Schmitz N: Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation. Blood 88: 3621-3625, 1996
Cooley HM, Snowden JA, Grigg AP, Wicks IP: Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy. Arthritis & Rheumatism 40:1712-1715, 1997
Passweg JR, Tyndall A: Autologous stem cell transplantation for autoimmune disease (abstract). Bone Marrow Transplant 23(Suppl. 1):S35, #110, 1999
Brodsky RA, Petri M, Smith BD, Seifter EJ, Spivak JL, Styler M, Dang CV, Brodsky I, Jones RJ: Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease. Ann Intern Med 129:1031-1035, 1998
Curtis RE, Rowlings PA, Deeg HJ, Shriner DA, Socié G, Travis LB, Horowitz MM, Witherspoon RP, Hoover RN, Sobocinski KA, Fraumeni JF, Jr., Boice JD, Jr., Schoch HG, Sale GE, Storb R, Travis WD, Kolb H-J, Gale RP, Passweg JR: Solid cancers after bone marrow transplantation. N Engl J Med 336:897-904, 1997
Stone RM, Neuberg D, Soiffer R, Takvorian T, Whelan M, Rabinowe SN, Aster JC, Leavitt P, Mauch P, Freedman AS, Nadler LM: Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 12:2535-2542, 1994
Govindarajan R, Jagannath S, Flick JT, Vesole DH, Sawyer J, Barlogie B, Tricot G: Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma. Br J Haematol 95:349-353, 1996
Taylor PR, Jackson GH, Lennard AL, Hamilton PJ, Proctor SJ: Low incidence of myelodysplastic syndrome following transplantation using autologous non-cryopreserved bone marrow. Leukemia 11:1650-1653, 1997
Laughlin MJ, McGaughey DS, Crews JR, Chao NJ, Rizzieri D, Ross M, Gockerman J, Cirrincione C, Berry D, Mills L, Defusco P, LeGrand S, Peters WP, Vredenburgh JJ: Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant. J Clin Oncol 16:1008-1012, 1998
van Gelder M, Mulder AH, van Bekkum DW: Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation. Transplantation 62:810-818, 1996
Marmont AM: Stem cell transplantation for severe autoimmune disorders, with special reference to rheumatic diseases. J Rheumatol 24:13-18, 1997
McKendry RJ, Huebsch L, Leclair B: Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13-year followup. Arthritis & Rheumatism 39: 1246-1253, 1996
Otero Lopez-Cubero S, Sullivan KM, McDonald GB: Course of Crohn's disease after allogeneic marrow transplantation. Gastroenterology 114:433-440, 1998
Storb R, Etzioni R, Anasetti C, Appelbaum FR, Buckner CD, Bensinger W, Bryant E, Clift R, Deeg HJ, Doney K, Flowers M, Hansen J, Martin P, Pepe M, Sale G, Sanders J, Singer J, Sullivan KM, Thomas ED, Witherspoon RP: Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia. Blood 84:941-949, 1994
Walters MC, Patience M, Leisenring W, Rogers ZR, Dinndorf P, Davies SC, Roberts IAG, Yeager A, Kurtzberg J, Bunin N, Scott JP, Wall DA, Wayne AS, Wiley J, Darbyshire PJ, Mentzer WC, Smith FO, Sullivan KM: Collaborative multicenter investigation of marrow transplantation for sickle cell disease: Current results and future directions. Biol Blood and Marrow Transplantation 3:310-315, 1997
Slattery JT, Clift RA, Buckner CD, Radich J, Storer B, Bensinger WI, Soll E, Anasetti C, Bowden R, Bryant E, Chauncey T, Deeg HJ, Doney KC, Flowers M, Gooley T, Hansen JA, Martin PJ, McDonald GB, Nash R, Petersdorf EW, Sanders JE, Schoch G, Stewart P, Storb R, Sullivan KM, Thomas ED, Witherspoon RP, Appelbaum FR: Marrow transplantation for chronic myeloid leukemia: The influence of plasma busulfan levels on the outcome of transplantation. Blood 89:3055-3060, 1997
Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem H-P, Leisenring W, Shulman H: Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 89:3048-3054, 1997
McSweeney PA, Storb R: Mixed chimerism: preclinical studies and clinical applications (Review). Biol Blood Marrow Transplant 5:192-203, 1999
Clift RA, Buckner CD, Thomas ED, Bensinger WI, Bowden R, Bryant E, Deeg HJ, Doney KC, Fisher LD, Hansen JA, Martin P, McDonald GB, Sanders JE, Schoch G, Singer J, Storb R, Sullivan KM, Witherspoon RP, Appelbaum FR: Marrow transplantation for chronic myeloid leukemia: A randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 84:2036-2043, 1994
Sullivan KM: Longterm followup and quality of life after hematopoietic stem cell transplantation. J Rheumatol 24:46-52, 1997
Sullivan KM, Mori M, Sanders J, Siadak M, Witherspoon RP, Anasetti C, Appelbaum FR, Bensinger W, Bowden R, Buckner CD, Clark J, Crawford S, Deeg HJ, Doney K, Flowers M, Hansen J, Loughran T, Martin P, McDonald G, Pepe M, Petersen FB, Schuening F, Stewart P, Storb R: Late complications of allogeneic and autologous marrow transplantation (Review). Bone Marrow Transplant 10:127-134, 1992
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Nash, R.A. Prospects of Stem Cell Transplantation in Autoimmune Diseases. J Clin Immunol 20, 38–45 (2000). https://doi.org/10.1023/A:1006690526998
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DOI: https://doi.org/10.1023/A:1006690526998