Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

Loh, Yvonne; Oyama, Yu; Statkute, Laisvyde; Quigley, Kathleen; Yaung, Kimberly; Gonda, E.; Barr, Walter G.; Jovanovic, Borko; Craig, Robert M.; Stefoski, Dusan; Cohen, Bruce A.; Burt, Richard K.

doi:10.1182/blood-2006-07-035766

Cited by 134 publications

(145 citation statements)

References 60 publications

(56 reference statements)

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“…Autoimmune thyroid disease occurred in half of these cases. Secondary autoimmune disease was more common in those patients who underwent HSCT for systemic lupus erythematosus, and was less frequent in those who underwent HSCT for other illnesses, including MS. Other autoimmune phenomenon ,such as immune cytopenias, predominantly immune thrombocytopenic purpura (ITP), may occur up to several years post-transplant [63].…”

Section: Lesson 9: the Reconstituted Immune System Retains A Predispomentioning

confidence: 99%

“…A retrospective registry review reports a 9 % incidence of secondary autoimmunity among patients who received ATG during HSCT conditioning, but secondary autoimmune disease occurred in only 4 % of patients who did not receive a lymphocyte-depleting agent [62]. Alemtuzumab may be more potent at inducing secondary autoimmune phenomenon, as the incidence of secondary autoimmunity was noted to be 16 % when alemtuzumab was included in the conditioning regimen, but only 2 % with ATG in a large single-center experience [63].…”

Section: Lesson 9: the Reconstituted Immune System Retains A Predispomentioning

confidence: 99%

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Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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Reports from more than 600 hematopoietic stem cell transplants (HSCT) have appeared in the medical literature for the last 1 and one-half decades. The patient's own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the auto-destructive immune system. The immune system is regenerated from the infused autologous hematopoietic stem cells. Increasing clinical experience has refined patient selection criteria and management in the peri-transplant period leading to a reduction in treatment-related complications. HSCT, when used to treat patients with aggressive highly active multiple sclerosis, can reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients, in the absence of chronic treatment with disease-modifying agents. The top 10 lessons learned from the growing experience using HSCT for the treatment of multiple sclerosis are discussed.Keywords Hematopoietic stem cell transplantation . Multiple sclerosis . Autoimmunity . Immune ablation There are published reports of more than 600 bone marrowbased transplants performed primarily for the treatment of multiple sclerosis (MS). This review will focus on why and how the hematopoietic stem cell transplantation (HSCT) procedure is used and discuss some of the lessons that can be gleaned from the experience of using HSCT to treat MS.MS is an organ-specific autoimmune disease that results in exclusive central nervous system (CNS) demyelination and axonal damage. Early on, multifocal localized pockets of inflammation lead to transient neurologic dysfunction manifesting as a series of relapses followed by remissions, usually with complete recovery owing to adequate CNS repair. However, as the damage accumulates, repair becomes inadequate and leads to incomplete resolution of disability, culminating in a neurodegenerative process amid a sea of smoldering and changing inflammation. This is probably the underlying state for the clinical stage of secondary progressive MS (SP-MS), a phase characterized by relentless and progressive accumulation of neurological disability with dwindling evidence of discrete relapses [1].Targeting inflammation with interferon-β, glatiramer acetate, natalizumab, fingolimod, and other immune-modulating agents reduces the frequency of relapses, but the impact on delaying the onset, preventing or slowing the tempo of SP-MS remains uncertain [2][3][4]. Several other drugs are in late stage clinical trials and may provide new alternatives for some patients with relapsing-remitting MS (RR-MS). However, despite these therapeutic advances, a subset of patients seem refractory and rapidly develop severe neurological impairment, whereas other patients may have a slower progression of illness that ultimately results in marked functional disabilities. Only a single agent, mitoxantrone, has been shown to temporarily halt or slow the tempo of SP-MS [5,6], but even then, this occurs only in SP-MS patients who have highly act...

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Section: Lesson 9: the Reconstituted Immune System Retains A Predispomentioning

confidence: 99%

Section: Lesson 9: the Reconstituted Immune System Retains A Predispomentioning

confidence: 99%

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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“…Most frequently, antibody-associated organspecific ADs such as thyroiditis (32), immune thrombocytopenia, autoimmune hemolytic anemia (33), or myasthenia gravis have been reported (34). In a single-center North American retrospective study (35) ATG or alemtuzumab (CD-52 antibodies). Two other cases of SSc patients were studied after HSCT for secondary onset of immune thrombocytopenia, followed by Graves' disease and SLE with antiphospholipid syndrome in the first one (36) and myasthenia gravis in the other (37).…”

Section: Secondary Ads Occurring After Hsctmentioning

confidence: 99%

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

2012

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“…In addition, progressive immunosuppressive therapy may lead to the development of serious infection, cumulative drug toxicity, and an increased risk of cardiovascular disease and malignancy (4). In the last decade, hematopoietic stem cell transplantation (HSCT) has been reported as a promising therapy to achieve treatment-free, long-term remission in lupus (5), but the rates of relapse and treatmentrelated toxicity are high, as are the rates of the development of a secondary autoimmune disorder (6). Therefore, newer therapeutic approaches with enhanced efficacy and less toxicity than current treatment standards are urgently needed.…”

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confidence: 99%

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

Sun

Wang

Liang

et al. 2010

Arthritis & Rheumatism

424

310

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Objective. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown marked therapeutic effects in a number of diseases in animal studies, based on their potential for self-renewal and differentiation. No data are available on the effectiveness of UC MSC transplantation (MSCT) in human autoimmune disease. This study was undertaken to assess the efficacy and safety of allogeneic UC MSCT in patients with severe and treatment-refractory systemic lupus erythematosus (SLE).Methods. We conducted a single-arm trial that involved 16 SLE patients whose disease was refractory to standard treatment or who had life-threatening visceral involvement. All of the patients gave consent and underwent UC MSCT. Clinical changes were evaluated before and after transplantation using the SLE Disease Activity Index (SLEDAI), measurement of serum antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, serum complement C3 and C4, and albumin levels, and assessment of and renal function. Evaluation of potential mechanisms of MSCT effects focused on the percentage of peripheral blood Treg cells and serum levels of cytokines.Results. From April 2007 to July 2009, a total of 16 patients with active SLE were enrolled and underwent UC MSCT. The median followup time after MSCT was 8.25 months (range 3-28 months). Significant improvements in the SLEDAI score, levels of serum ANA, anti-dsDNA antibody, serum albumin, and complement C3, and renal function were observed. Clinical remission was accompanied by an increase in peripheral Treg cells and a re-established balance between Th1-and Th2-related cytokines. Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.Conclusion. Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines. These data provide a foundation for conducting a randomized controlled trial of this new therapy for severe and treatment-refractory SLE.Systemic lupus erythematosus (SLE) is an inflammatory disease with protean manifestations, ranging from relatively minor skin and joint symptoms to severe life-threatening major organ involvement, such as nephritis and neuropsychiatric complications (1). It is characterized by the presence of autoreactive T and B lymphocytes, with polyclonal activation of B cells and the consequent production of autoantibodies by plasma ClinicalTrials.gov identifier: NCT00698191.

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Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

Cited by 134 publications

References 60 publications

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus

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