Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with a relapsing and remitting course, which is often treatable with immunosuppressive therapy. However, we describe a patient with severe and refractory thrombotic thrombocytopaenic purpura (TTP) secondary to SLE that did not respond to high dose corticosteroids, cyclophosphamide (CyC), vincristine, rituximab, and plasmapheresis. She eventually required haematopoietic stem cell transplantation (HSCT) to bring the disease under control. She is in disease remission three years post-stem cell transplantation. HSCT is a possible treatment option for severe and refractory SLE when conventional therapy has failed. HSCT for other rheumatologic diseases is also reviewed.
ThewissenMStinissenP. New concepts on the pathogenesis of autoimmune diseases: A role for immune homeostasis, immunoregulation, and immunosenescence. Crit Rev Immunol2008;28:363–76.
2.
NelsonJLTorrezRLouieFMChoeOSStorbRSullivanKM. Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation. J Rheumatol Suppl1997;48:23–9.
3.
YangWZhaoMHirankarnNLauCSMokCCChanTM. ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai. Hum Mol Genet2009;18:2063–70.
4.
RahmanAIsenbergDA. Systemic lupus erythematosus. N Engl J Med2008;358:929–39.
5.
CooperGSDooleyMATreadwellELSt ClairEWParksCGGilkesonGS. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. Arthritis Rheum1998;41:1714–24.
AndradeFCasciola-RosenLRosenA. Apoptosis in systemic lupus erythematosus. Clinical implications. Rheum Dis Clin North Am2000;26:215–27.
8.
MunozLEGaiplUSFranzSSheriffAVollREKaldenJR. SLE–a disease of clearance deficiency?Rheumatology (Oxford). 2005;44:1101–7.
9.
ZimmermanRRadhakrishnanJValeriAAppelG. Advances in the treatment of lupus nephritis. Annu Rev Med2001;52:63–78.
10.
FurstDE. Stem cell transplantation for autoimmune disease: Progress and problems. Curr Opin Rheumatol2002;14:220–4.
11.
IppolitoAPetriM. An update on mortality in systemic lupus erythematosus. Clin Exp Rheumatol2008;26:S72–9.
12.
ChangCCShihTYChuSJKuoSYChenCMHsuCM. Lupus in Chinese male: A retrospective study of 61 patients. Zhonghua Yi Xue Za Zhi (Taipei)1995;55: 143–50.
13.
MokCCMakAChuWPToCHWongSN. Long-term survival of southern Chinese patients with systemic lupus erythematosus: A prospective study of all age-groups. Medicine (Baltimore). 2005;84:218–24.
14.
WallaceDJHahnBH. Dubois' lupus erythematosus. 7th ed.Philadelphia: Lippincott Williams & Wilkins; 2007. p. 1414.
15.
NossentJCikesNKissEMarchesoniANassonovaVMoscaM. Current causes of death in systemic lupus erythematosus in Europe, 2000–2004: Relation to disease activity and damage accrual. Lupus2007;16:309–17.
16.
ToCHMokCCTangSSYingSKWongRWLauCS. Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis. Lupus2009;18:1267–75.
17.
BernatskySBoivinJFJosephLManziSGinzlerEGladmanDD. Mortality in systemic lupus erythematosus. Arthritis Rheum2006;54:2550–7.
18.
TyndallAGratwohlA. 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 Transplant1997;19:643–5.
19.
MarmontAM. Immune ablation with stem-cell rescue: A possible cure for systemic lupus erythematosus?Lupus1993;2:151–6.
20.
IkeharaSGoodRANakamuraTSekitaKInoueSOoMM. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA1985;82:2483–7.
21.
MeloniGCapriaSVignettiMMandelliFModenaV. Blast crisis of chronic myelogenous leukemia in long-lasting systemic lupus erythematosus: Regression of both diseases after autologous bone marrow transplantation. Blood1997;89:4659.
22.
SchachnaLRyanPFSchwarerAP. Malignancy-associated remission of systemic lupus erythematosus maintained by autologous peripheral blood stem cell transplantation. Arthritis Rheum1998;41:2271–2.
23.
SnowdenJAPattonWNO'DonnellJLHannahEEHartDN. Prolonged remission of longstanding systemic lupus erythematosus after autologous bone marrow transplant for non-Hodgkin's lymphoma. Bone Marrow Transplant1997;19(12):1247–50.
24.
MarmontAM. Immune ablation followed by allogeneic or autologous bone marrow transplantation: A new treatment for severe autoimmune diseases?Stem Cells. 1994;12:125–35.
25.
BurtRKMarmontAOyamaYSlavinSArnoldRHiepeF. Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: The evolution from myeloablative to lymphoablative transplant regimens. Arthritis Rheum2006;54:3750–60.
26.
MuraroPADouekDCPackerAChungKGuenagaFJCassiani-IngoniR. Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients. J Exp Med2005;201:805–16.
27.
MackallCLBareCVGrangerLASharrowSOTitusJAGressRE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol1996;156:4609–16.
28.
AlexanderTThielARosenOMassenkeilGSattlerAKohlerS. Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system. Blood2009;113:214–23.
TraynorAECorbridgeTCEaganAEBarrWGLiuQOyamaY. Prevalence and reversibility of pulmonary dysfunction in refractory systemic lupus: Improvement correlates with disease remission following hematopoietic stem cell transplantation. Chest2005;127:1680–9.
31.
StatkuteLTraynorAOyamaYYaungKVerdaLKrosnjarN. Antiphospholipid syndrome in patients with systemic lupus erythematosus treated by autologous hematopoietic stem cell transplantation. Blood2005;106:2700–9.
FargeDLabopinMTyndallAFassasAMancardiGLVan LaarJ. Autologous hematopoietic stem cell transplantation for autoimmune diseases: An observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica2010;95:284–92.
34.
KrügerWBohliusJCornelyOEinseleHHebartHMassenkeilG. Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology. Ann Oncol2005;16:1381–90.
35.
SocieGBlazarBR. Acute graft-versus-host disease: From the bench to the bedside. Blood2009;114:4327–36.
36.
VerburgRJKruizeAAvan den HoogenFHFibbeWEPetersenEJPreijersF. 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 Rheum2001;44:754–60.
37.
TyndallASaccardiR. Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: Results from phase I/II studies, prospective randomized trials and future directions. Clin Exp Immunol2005;141:1–9.
38.
PasswegJTyndallA. Autologous stem cell transplantation in autoimmune diseases. Semin Hematol2007;44:278–85.
39.
SeiboldJRFurstDEClementsPJ. Why everything (or nothing) seems to work in the treatment of scleroderma. J Rheumatol1992;19:673–6.
40.
PappGHorvathIFBarathSGyimesiESipkaSSzodorayP. Altered T-cell and regulatory cell repertoire in patients with diffuse cutaneous systemic sclerosis. Scand J Rheumatol2011;40:205–10.
41.
RadstakeTRDJvan BonLBroenJHussianiAHesselstrandRWuttgeDM. The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes. PloS one2009;4:e5903.
42.
BurtRKMilanettiF. Hematopoietic stem cell transplantation for systemic sclerosis: History and current status. Curr Opin Rheumatol2011;23:519–29.
43.
IoannidisJPAVlachoyiannopoulosPGHaidichABMedsgerTALucasMMichetCJ. Mortality in systemic sclerosis: An international meta-analysis of individual patient data. Am J Med2005;118:2–10.
44.
BurtRKShahSJDillKGrantTGheorghiadeMSchroederJ. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): An open-label, randomised phase 2 trial. Lancet2011;378:498–506.
45.
SnowdenJASaccardiRAllezMArdizzoneSArnoldRCerveraR. Haematopoietic SCT in severe autoimmune diseases: Updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant2012;47:770–90.
46.
ForfiaPRFisherMRMathaiSCHousten-HarrisTHemnesARBorlaugBA. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med2006;174:1034–41.
47.
BurtRKShahSJGheorghiadeMRudermanESchroederJ. Hematopoietic stem cell transplantation for systemic sclerosis: If you are confused, remember: “It is a matter of the heart”. J Rheumatol2012;39:206–9.
48.
FargeD. Autologous stem cell transplantation in the treatment of systemic sclerosis: Report from the EBMT/EULAR Registry. Ann Rheum Dis2004;63:974–81.
49.
VerrecchiaFLaboureauJVerolaORoosNPorcherRBrunevalP. Skin involvement in scleroderma–where histological and clinical scores meet. Rheumatology (Oxford)2007;46:833–41.
50.
VonkMCMarjanovicZvan den HoogenFHZoharSSchattenbergAVFibbeWE. Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis. Ann Rheum Dis2008;67:98–104.
51.
FargeDPasswegJvan LaarJMMarjanovicZBesenthalCFinkeJ. Autologous stem cell transplantation in the treatment of systemic sclerosis: Report from the EBMT/EULAR Registry. Ann Rheum Dis2004;63:974–81.
52.
SteenVDMedsgerTAJr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum1998;41:1613–9.
53.
TashkinDPElashoffRClementsPJGoldinJRothMDFurstDE. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med2006;354:2655–66.
54.
TsukamotoHNagafujiKHoriuchiTMitomaHNiiroHArinobuY. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: Predominant reconstitution of Th1 CD4+ T cells. Rheumatology (Oxford)2011;50:944–52.
55.
DaikelerTKötterITyndallCBApperleyJAttarbaschiAGuardiolaP. Haematopoietic stem cell transplantation for vasculitis including Behcet's disease and polychondritis: A retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature. Ann Rheum Dis2007;66:202–7.
56.
StatkuteLOyamaYBarrWGSufitRHoSVerdaL. Autologous non-myeloablative haematopoietic stem cell transplantation for refractory systemic vasculitis. Ann Rheum Dis2008;67:991–7.
57.
GillilandDGGribbenJG. Evaluation of the risk of therapy-related MDS/AML after autologous stem cell transplantation. Biol Blood Marrow Transplant2002; 8:9–16.
