Ten years have passed since the first published consensus statement on the use of hematopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease (AD) appeared. During that time, around 700 patients suffering from severe AD have undergone HSCT in the frame of phase I/II clinical trials from over 20 countries including the US. The majority have received an autologous HSCT using one of a limited number of regimens, consistent with the original consensus statement. Long-term drug-free remissions, remission then relapse, no response and treatment-related mortality (TRM) were seen in all the subgroups of AD. An overall TRM of 7% was observed, with marked variation between ADs, i.e. 11% in systemic lupus erythematosus (SLE) and only 1 patient in rheumatoid arthritis (RA). Phase III prospective, comparative randomized trials are running or being planned in multiple sclerosis (MS), systemic sclerosis (SSc), SLE and RA. Basic science programs are also being undertaken to study the immunological mechanisms underlying the clinical events observed.

1.
Marmont AM, Gratwohl A, Vischer T: Haemopoietic precursor-cell transplants for autoimmune diseases. Lancet 1995;345:978.
2.
Tyndall A, Gratwohl A: Blood and marrow stem cell transplants in auto-immune disease: A consensus report written on behalf of the European League against Rheumatism (EULAR) and the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1997;19:643–645.
3.
Sullivan KM, Furst DE: The evolving role of blood and marrow transplantation for the treatment of autoimmune diseases. J Rheumatol Suppl 1997;48:1–4.
4.
Hinterberger W, Hinterberger-Fischer M, Marmont A: Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favorably affects outcome after stem cell transplantation in human autoimmune diseases. Bone Marrow Transplant 2002;30:753–759.
5.
Slavin S, Nagler A, Varadi G, Or R: Graft vs. autoimmunity following allogeneic non-myeloablative blood stem cell transplantation in a patient with chronic myelogenous leukemia and severe systemic psoriasis and psoriatic polyarthritis. Exp Hematol 2000;28:853–857.
6.
Davidson A, Diamond B: Autoimmune diseases. N Engl J Med 2001;345:340–350.
7.
Medzhitov R, Janeway CA Jr: Decoding the patterns of self and nonself by the innate immune system. Science 2002;296:298–300.
8.
van Bekkum DW: Stem cell transplantation for autoimmune disorders. Preclinical experiments. Best Pract Res Clin Haematol 2004;17:201–222.
9.
Roep BO, Atkinson M: Animal models have little to teach us about type 1 diabetes: 1. In support of this proposal. Diabetologia 2004;47:1650–1656.
10.
Ikehara S: Treatment of autoimmune diseases by hematopoietic stem cell transplantation. Exp Hematol 2001;29:661–669.
11.
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 1991;8:333–338.
12.
Silman AJ, MacGregor AJ, Thomson W, Holligan S, Carthy D, Farhan A, et al: Twin concordance rates for rheumatoid arthritis: Results from a nationwide study. Br J Rheumatol 1993;32:903–907.
13.
Tisch R, McDevitt H: Insulin-dependent diabetes mellitus. Cell 1996;85:291–297.
14.
Marmont AM: Stem cell transplantation for autoimmune disorders. Coincidental autoimmune disease in patients transplanted for conventional indications. Best Pract Res Clin Haematol 2004;17:223–232.
15.
Sturfelt G, Lenhoff S, Sallerfors B, Nived O, Truedsson L, Sjoholm AG: Transplantation with allogenic bone marrow from a donor with systemic lupus erythematosus (SLE): Successful outcome in the recipient and induction of an SLE flare in the donor. Ann Rheum Dis 1996;55:638–641.
16.
Openshaw H, Lund BT, Kashyap A, Atkinson R, Sniecinski I, Weiner LP, et al: Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: Report of toxicity and immunological monitoring. Biol Blood Marrow Transplant 2000;6(5A):563–575.
17.
McKendry RJ, Huebsch L, Leclair B: Progression of rheumatoid arthritis following bone marrow transplantation. A case report with a 13-year follow-up. Arthritis Rheum 1996;39:1246–1253.
18.
Durez P, Toungouz M, Schandene L, Lambermont M, Goldman M: Remission and immune reconstitution after T-cell-depleted stem-cell transplantation for rheumatoid arthritis. Lancet 1998;352:881.
19.
McColl G, Kohsaka H, Szer J, Wicks I: High-dose chemotherapy and syngeneic hemopoietic stem-cell transplantation for severe, seronegative rheumatoid arthritis. Ann Intern Med 1999;131:507–509.
20.
Pavletic SZ, Odell JR, Pirruccello SJ, Ursick MM, Haire CE, Sharp JG, et al: Intensive immunoablation and autologous blood stem cell transplantation in patients with refractory rheumatoid arthritis: the University of Nebraska experience. J Rheumatol Suppl 2001;64:13–20.
21.
Bingham SJ, Snowden J, McGonagle D, Richards S, Isaacs J, Morgan G, et al: Autologous stem cell transplantation for rheumatoid arthritis – interim report of 6 patients. J Rheumatol Suppl 2001;64:21–24.
22.
Verburg RJ, Kruize AA, van den Hoogen FH, Fibbe WE, Petersen EJ, Preijers F, et al: High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with rheumatoid arthritis: results of an open study to assess feasibility, safety, and efficacy. Arthritis Rheum 2001;44:754–760.
23.
Kim KC, Lee IH, Choi JH, Oh MR, Ahn MJ, Kim SY: Autologous stem cell transplantation in the treatment of refractory rheumatoid arthritis. J Korean Med Sci 2002;17:129–132.
24.
Moore J, Brooks P, Milliken S, Biggs J, Ma D, Handel M, et al: A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis. Arthritis Rheum 2002;46:2301–2309.
25.
Lanza F, Dominici M, Govoni M, Moretti S, Campioni D, Corte RL, et al: Prolonged remission state of refractory adult onset Still’s disease following CD34-selected autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2000;25:1307–1310.
26.
Wulffraat N, van Royen A, Bierings M, Vossen J, Kuis W: Autologous haemopoietic stem-cell transplantation in four patients with refractory juvenile chronic arthritis. Lancet 1999;353:550–553.
27.
Quartier P, Prieur AM, Fischer A: Haemopoietic stem-cell transplantation for juvenile chronic arthritis. Lancet 1999;353:1885–1886.
28.
Nakagawa R, Kawano Y, Yoshimura E, Suzuya H, Watanabe T, Kanamaru S, et al: Intense immunosuppression followed by purified blood CD34+ cell autografting in a patient with refractory juvenile rheumatoid arthritis. Bone Marrow Transplant 2001;27:333–336.
29.
Tyndall A, Black C, Finke J, Winkler J, Mertlesmann R, Peter HH, et al: Treatment of systemic sclerosis with autologous haemopoietic stem cell transplantation. Lancet 1997;349:254.
30.
Martini A, Maccario R, Ravelli A, Montagna D, De Benedetti F, Bonetti F, et al: Marked and sustained improvement 2 years after autologous stem cell transplantation in a girl with systemic sclerosis. Rheumatology (Oxford) 1999;38:773.
31.
McSweeney PA, Nash RA, Sullivan KM, Storek J, Crofford LJ, Dansey R, et al: High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes. Blood 2002;100:1602–1610.
32.
Farge D, Marolleau JP, Zohar S, Marjanovic Z, Cabane J, Mounier N, et al: Autologous bone marrow transplantation in the treatment of refractory systemic sclerosis: early results from a French multicentre phase I–II study. Br J Haematol 2002;119:726–739.
33.
Marmont AM, van Lint MT, Gualandi F, Bacigalupo A: Autologous marrow stem cell transplantation for severe systemic lupus erythematosus of long duration. Lupus 1997;6:545–548.
34.
Musso M, Porretto F, Crescimanno A, Bondi F, Polizzi V, Scalone R et al: Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome. Lupus 1998;7:492–494.
35.
Fouillard L, Gorin NC, Laporte JP, Leon A, Brantus JF, Miossec P: Control of severe systemic lupus erythematosus after high-dose immunosuppressive therapy and transplantation of CD34+-purified autologous stem cells from peripheral blood. Lupus 1999;8:320–323.
36.
Trysberg E, Lindgren I, Tarkowski A: Autologous stem cell transplantation in a case of treatment resistant central nervous systemic lupus. Ann Rheum Dis 2000;59:236–238.
37.
Shaughnessy PJ, Ririe DW, Ornstein DL, Kissack B, Bickford DJ, Molina R, et al: Graft failure in a patient with systemic lupus erythematosus (SLE) treated with high-dose immunosuppression and autologous stem cell rescue. Bone Marrow Transplant 2001;27:221–224.
38.
Rosen O, Hiepe F, Massenkeil G, Thiel A, Arnold R: Relapse of systemic lupus erythematosus. Lancet 2001;357:807–808.
39.
Wulffraat NM, Sanders EA, Kamphuis SS, Rijkers GT, Kuis W, Lilien M, et al: Prolonged remission without treatment after autologous stem cell transplantation for refractory childhood systemic lupus erythematosus. Arthritis Rheum 2001;44:728–731.
40.
Brunner M, Greinix HT, Redlich K, Knobl P, Smolen J, Leitner G, et al: Autologous blood stem cell transplantation in refractory systemic lupus erythematosus with severe pulmonary impairment: A case report. Arthritis Rheum 2002;46:1580–1584.
41.
Traynor AE, Barr WG, Rosa RM, Rodriguez J, Oyama Y, Baker S, et al: Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients. Arthritis Rheum 2002;46:2917–2923.
42.
Myllykangas-Luosujarvi R, Jantunen E, Kaipiainen-Seppanen O, Mahlamaki E, Nousiainen T: Autologous peripheral blood stem cell transplantation in a patient with severe mixed connective tissue disease. Scand J Rheumatol 2000;29:326–327.
43.
Baron F, Ribbens C, Kaye O, Fillet G, Malaise M, Beguin Y: Effective treatment of Jo-1-associated polymyositis with T-cell-depleted autologous peripheral blood stem cell transplantation. Br J Haematol 2000;110:339–342.
44.
Bingham S, Griffiths B, McGonagle D, Snowden JA, Morgan G, Emery P: Autologous stem cell transplantation for rapidly progressive Jo-1-positive polymyositis with long-term follow-up. Br J Haematol 2001;113:840–841.
45.
Burt RK, Traynor AE, Cohen B, Karlin KH, Davis FA, Stefoski D, et al: T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: Report on the first three patients. Bone Marrow Transplant 1998;21:537–541.
46.
Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, et al: Autologous stem cell transplantation in progressive multiple sclerosis – an interim analysis of efficacy. J Clin Immunol 2000;20:24–30.
47.
Kozak T, Havrdova E, Pit’ha J, Gregora E, Pytlik R, Maaloufova J, et al: High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis. Bone Marrow Transplant 2000;25:525–531.
48.
Burt RK, Traynor A, Oyama Y, Craig R: High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease. Blood 2003;101:2064– 2066.
49.
Rosen O, Thiel A, Massenkeil G, Hiepe F, Haupl T, Radtke H, et al: Autologous stem-cell transplantation in refractory autoimmune diseases after in vivo immunoablation and ex vivo depletion of mononuclear cells. Arthritis Res 2000;2:327–336.
50.
Rabusin M, Andolina M, Maximova N, Lepore L, Parco S, Tuveri G, et al: Immunoablation followed by autologous hematopoietic stem cell infusion for the treatment of severe autoimmune disease. Haematologica 2000;85 (suppl):81–85.
51.
Musso M, Porretto F, Crescimanno A, Bondi F, Polizzi V, Scalone R: Intense immunosuppressive therapy followed by autologous peripheral blood selected progenitor cell reinfusion for severe autoimmune disease. Am J Hematol 2001;66:75–79.
52.
Gratwohl A, Passweg J, Gerber I, Tyndall A: Stem cell transplantation for autoimmune diseases. Best Pract Res Clin Haematol 2001;14:755–776.
53.
Saccardi R, Tyndall A, Coghlan G, Denton C, Edan G, Emdin M, et al: Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis. Bone Marrow Transplant 2004;34:877–881.
54.
Binks M, Passweg JR, Furst D, McSweeney P, Sullivan K, Besenthal C, et al: Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis 2001;60:577–584.
55.
Farge D, Passweg J, van Laar JM, Marjanovic Z, Besenthal C, Finke J, et al: Autologous stem cell transplantation in the treatment of systemic sclerosis: Report from the EBMT/EULAR Registry. Ann Rheum Dis 2004;63:974–981.
56.
Snowden JA, Passweg J, Moore JJ, Milliken S, Cannell P, Van Laar J, et al: Autologous hemopoietic stem cell transplantation in severe rheumatoid arthritis: a report from the EBMT and ABMTR. J Rheumatol 2004;31:482–488.
57.
Fassas A, Passweg JR, Anagnostopoulos A, Kazis A, Kozak T, Havrdova E, et al: Hematopoietic stem cell transplantation for multiple sclerosis. A retrospective multicenter study. J Neurol 2002;249:1088–1097.
58.
Wulffraat NM, de Kleer IM, Prakken BJ, Kuis W: Stem cell transplantation for autoimmune disorders. Refractory juvenile idiopathic arthritis. Best Pract Res Clin Haematol 2004;17:277–289.
59.
Jayne D, Passweg J, Marmont A, Farge D, Zhao X, Arnold R, et al: Autologous stem cell transplantation for systemic lupus erythematosus. Lupus 2004;13:168–176.
60.
Jayne D, Tyndall A: Autologous stem cell transplantation for systemic lupus erythematosus. Lupus 2004;13:359–365.
61.
Hensel M, Breitbart A, Ho AD: Autologous hematopoietic stem-cell transplantation for Behçet’s disease with pulmonary involvement. N Engl J Med 2001;344:69.
62.
Rossi G, Moretta A, Locatelli F: Autologous hematopoietic stem cell transplantation for severe/refractory intestinal Behçet disease. Blood 2004;103:748–750.
63.
Voltarelli JC, Oliveira MC, Stracieri AB, Godoi DF, Moraes DA, Coutinho MA, et al: Haematopoietic stem cell transplantation for refractory Takayasu’s arteritis. Rheumatology (Oxford) 2004;43:1308–1309.
64.
Kalwak K, Gorczynska E, Toporski J, Turkiewicz D, Slociak M, Ussowicz M, et al: Immune reconstitution after haematopoietic cell transplantation in children: Immunophenotype analysis with regard to factors affecting the speed of recovery. Br J Haematol 2002;118:74–89.
65.
Peggs KS, Verfuerth S, Pizzey A, Khan N, Moss P, Goldstone AH, et al: Reconstitution of T-cell repertoire after autologous stem cell transplantation: Influence of CD34 selection and cytomegalovirus infection. Biol Blood Marrow Transplant 2003;9:198–205.
66.
Douek DC, Vescio RA, Betts MR, Brenchley JM, Hill BJ, Zhang L, et al: Assessment of thymic output in adults after haematopoietic stem-cell transplantation and prediction of T-cell reconstitution. Lancet 2000;355:1875–1881.
67.
Crippa F, Holmberg L, Carter RA, Hooper H, Marr KA, Bensinger W, et al: Infectious complications after autologous CD34-selected peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2002;8:281–289.
68.
Aubert G, Hassan-Walker AF, Madrigal JA, Emery VC, Morte C, Grace S, et al: Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants. J Infect Dis 2001;184:955–963.
69.
Einsele H, Bertz H, Beyer J, Kiehl MG, Runde V, Kolb HJ, et al: Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies – guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol 2003;82(suppl 2):S175–S185.
70.
Petri M, Jones RJ, Brodsky RA: High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Arthritis Rheum 2003;48:166–173.
71.
Wedderburn LR, Jeffery R, White H, Patel A, Varsani H, Linch D, Murray K, Woo P: Autologous stem cell transplantation for paediatric-onset polyarteritis nodosa: changes in autoimmune phenotype in the context of reduced diversity of the T- and B-cell repertoires, and evidence for reversion from the CD45RO(+) to RA(+) phenotype. Rheumatology 2001;40: 1299–1307.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.