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

Slavin, Shimon; Nagler, Arnon; Váradi, Gábor; Or, Reuven

doi:10.1016/s0301-472x(00)00172-7

Cited by 108 publications

(61 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total elimination and a cure are often only possible using allo-HCT, where of immunosuppression in a patient receiving allo-HCT to treat leukaemia 20 . There are two documented case reports of non-myeloablative allogeneic transplants for Evans' syndrome, a disease characterized by combined autoimmune thrombocytopenia and autoimmune haemolytic anaemia.…”

Section: Immune-mediated Destruction Of Autoreactive T and B Cellsmentioning

confidence: 99%

Treatment of severe autoimmune disease by stem-cell transplantation

Sykes

Nikolic

2005

Nature

212

148

View full text Add to dashboard Cite

Transplantation of haematopoietic stem cells -cells capable of self renewing and reconstituting all types of blood cell -can treat numerous lethal diseases, including leukaemias and lymphomas. It may now be applicable for the treatment of severe autoimmune diseases, such as therapy-resistant rheumatoid arthritis and multiple sclerosis. Studies in animal models show that the transfer of haematopoietic stem cells can reverse autoimmunity, and several mechanistic pathways may explain this phenomenon. The outcome of ongoing clinical trials, as well as of studies in patients and animal models, will help to determine the role that stem-cell transplantation can play in the treatment of autoimmune diseases.In this article, we review the mechanisms by which HCT might induce tolerance to allo-and autoantigens and discuss recent advances that provide hope for better treatment of severe refractory autoimmune disease. The potential for tissue regeneration using this process is also discussed. Animal models provide the rationale for HCTSusceptibility to autoimmune diseases appears to reside in haematopoietic cells. Transplantation of bone-marrow cells from lupus-prone NZB mice into lethally irradiated non-susceptible strains induced the lupus syndrome 1 . This transfer of immune diseases with haematopoietic cells was subsequently confirmed for many autoimmune diseases, including other murine models of systemic lupus erythematosus (SLE), experimental autoimmune encephalomyelitis (EAE), adjuvant arthritis, antiphospholipid syndrome and type 1 diabetes 2 . Resistance to autoimmune diseases could also be transferred to susceptible strains by haematopoietic cells. In mice, HCT from disease-resistant allogeneic animals (allo-HCT) prevented the development of SLE, type 1 diabetes, EAE and other autoimmune diseases 3,4 .Although the prevention of autoimmunity might some day be clinically feasible, at the moment we cannot predict such diseases accurately enough to justify the use of toxic preventive treatments. Unfortunately, animal studies show that preventing the onset of autoimmunity is much easier then reversing established disease. As of 2004, for example, more than 195 methods for preventing or delaying the onset of type 1 diabetes in non-obese diabetic (NOD) mice had been identified 5 . But only a few therapeutic approaches have been effective in reversing established SLE and type 1 diabetes in mice, one of which is allo-HCT 6,7 .In animals, syngeneic HCT (that is, HCT from a genetically identical donor) can be used instead of auto-HCT. For simplicity we will refer to syngeneic HCT as auto-HCT. Although allo-HCT was reliably effective in reversing autoimmunity in animals, auto-HCT did not successfully reverse type 1 diabetes or SLE. However, varying levels of disease remission were achieved following auto-HCT in models of myasthenia gravis 8 , adjuvant arthritis 9 and EAE 10 . Allo-HCT was superior in the therapy of EAE. Auto-HCT was most successful at early dis-

show abstract

Section: Immune-mediated Destruction Of Autoreactive T and B Cellsmentioning

confidence: 99%

Treatment of severe autoimmune disease by stem-cell transplantation

Sykes

Nikolic

2005

Nature

212

148

View full text Add to dashboard Cite

show abstract

“…7,11 Significant acute and chronic GVHD in CST can lead to the durable remission of psoriasis, but may also cause the death of patients. Severe, sometimes lethal, GVHD, or the introduction of another immune dysfunction to HSCT recipients, should be avoided in the treatment of benign autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Theoretical graftversus-autoimmunity (GVA) effects due to the activation and reconstitution of donor T cells also support the effectiveness of allo-SCT against autoimmune diseases. 2,7 However, its significant treatment-related mortality has limited its application to life-threatening cases.…”

mentioning

confidence: 99%

Induction of graft-versus-autoimmune (GVA) disease effect against refractory psoriasis by complete donor-type chimerism and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Kojima¹,

Kami²,

Kim³

et al. 2003

Bone Marrow Transplant

View full text Add to dashboard Cite

Summary:A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reducedintensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graftversus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment. Bone Marrow Transplantation (2003) 32, 439-442. doi:10.1038/sj.bmt.1704146 Keywords: reduced-intensity stem cell transplantation; psoriasis; graft-versus-autoimmunity effect; graft-versushost disease Autologous stem cell transplantation (auto-SCT) has attracted attention for the treatment of severe lifethreatening autoimmune diseases, which include a stem cell disorder as a component. The background concept is that ablation of the diseased immune system followed by hematopoietic reconstitution with self-stem cells should restore normal immunity without attacking self-epitopes. Long-term remission and improvement have been observed in some cases after auto-SCT against autoimmune diseases. 1-6 Although auto-SCT has fewer toxicities and complications than allo-SCT, it is limited by the common recurrence of the primary diseases, especially in recipients of unmanipulated autografts. On the other hand, allo-SCT has been used to treat fatal disorders, both malignant and nonmalignant, as a curative approach. Theoretical graftversus-autoimmunity (GVA) effects due to the activation and reconstitution of donor T cells also support the effectiveness of allo-SCT against autoimmune diseases. 2,7 However, its significant treatment-related mortality has limited its application to life-threatening cases.Reduced-intensity stem cell transplantation (RIST), a new transplantation method with nonmyeloablative preparative regimens, has been developed to reduce regimenrelated toxicity (RRT) without spoiling the antitumor effect of allo-SCT. 8 The safety and efficacy of RIST have been demonstrated at our institution, with a 1-ye...

show abstract

“…24 Further evidence of this comes from a report of psoriasis/psoriatic arthritis that relapsed post-HSCT concurrent with increasing host chimerism and then resolved with discontinuation of immune suppression and reversion to donor chimerism; 25 it is also supported by another case report of psoriasis, which had initially resolved post transplant and then relapsed but resolved concurrent with a GVHD flare. 26 In the latter case, the reinduction of immune suppression to treat the GVHD confounds the analysis of whether this is truly a graft vs autoimmunity (GVA) effect or merely a response to standard autoimmune therapies.…”

Section: Rationalementioning

confidence: 94%