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New Zealand Stem Cell Clinic Auckland & Christchurch

Stem cell therapy in scleroderma

Curr Opin Rheumatol. 2002 Nov;14(6):711-6.


Rheumatology Division, UCLA Medical School, Los Angeles, California 90095, USA.


Scleroderma has a high mortality rate, especially in patients with early diffuse disease and poor prognostic features (such as high skin scores and internal organ involvement). In addition, there is no proven therapy for this disease. Finally, scleroderma has an autoimmune-related pathogenesis, particularly in early illness. In this setting, stem cell therapy is a reasonable potential choice. The rationale behind high-dose immunosuppressive therapy and stem cell transplantation in scleroderma, the regimens used, and the recent data from pilot studies are reviewed. The encouraging data, proper patient selection criteria, and appropriate therapy regimen make controlled studies appropriate, and such studies are currently under way in Europe and are soon to begin in the United States.

Autologous stem cell transplantation in scleroderma

Presse Med. 2021 Apr;50(1):104065.


Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Internal Medicine (UF04), MATHEC, Centre of reference for rare systemic autoimmune diseases (FAI2R); Université de Paris, EA 3518, Paris, France; McGill university, department of medicine, Montreal, QC, Canada. Electronic address:


Patients with severe rapidly progressive systemic sclerosis (SSc) have a poor prognosis. Standard immunosuppressive therapies may have modest effects on stabilizing disease, but they fail to improve overall survival. Hematopoietic stem cell transplant (HSCT) is the first treatment to induce disease-modifying therapeutic benefits in rapidly progressive SSc patients. HSCT in rapidly progressive SSc can induce regression of fibrosis in skin and lung, and increase survival. Initially, HSCT was associated with high treatment-related mortality rates. Improvements in patient screening, a better understanding of the risks associated with different treatment regimens, and centre experience have improved the AHSCT safety profile for patients with scleroderma.

Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma

N Engl J Med. 2018 Jan 4;378(1):35-47.


From the Duke University Medical Center (K.M.S., O.C., E.W.S.C.) and RTI International (D.W.), Durham, and Rho Federal Systems Division, Chapel Hill (L.K.-E., A.P., B.E., S.C.) - all in North Carolina


Background: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.

Methods: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.

Results: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.

Conclusions: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; number, NCT00114530 .).

Adult stem cells in the treatment of autoimmune diseases

Rheumatology (Oxford). 2006 Oct;45(10):1187-93.


Department of Rheumatology, University of Basel, Felix Platter Spital, Burgfelderstrasse 101, Basel 4012, Switzerland.


During the past 10 yrs, over 700 patients suffering from severe autoimmune disease (AD) have received an autologous haematopoietic stem cell transplant as treatment of their disorder with durable remission being obtained in around one-third. The most commonly transplanted ADs have been systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. A fewer number of patients have received an allogeneic transplant. The initially reported overall treatment-related mortality of 7% has since fallen, with no further cases being reported in systemic sclerosis or multiple sclerosis in the past 3 yrs. This is thought to be due to more careful patient selection. The phase I/II data has led to currently running prospective randomised trials in systemic sclerosis, multiple sclerosis and systemic lupus erythematosus in Europe and North America. Immune reconstitution data suggests a 'resetting' of autoimmunity in those patients achieving stable remission, rather than simply prolonged immunosuppression. Recent results from in vitro experiments, animal models and early human experience in severe acute graft vs host disease suggest that multipotent mesenchymal stromal cells obtained from the bone marrow and expanded ex vivo, may exert a clinically useful immunomodulatory effect. Such cells are immune privileged and apparently of low toxicity. Further characterization of these cells and consideration of their possible clinical application in AD is underway.

Cell therapy for autoimmune diseases

Arthritis Res Ther. 2007;9(2):206. doi: 10.1186/ar2128.


Stem Cell Biology Section, Kennedy Institute of Rheumatology, Imperial College Faculty of Medicine, London, UK.


Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases.

Remission of a long-lasting sarcoidosis after allogeneic hematopoietic stem cell transplantation

JAAD Case Rep. 2016 Sep; 2(5): 408–410.


Department of Dermatology, Centre Hospitalier de Valence, Valence, France


Sarcoidosis is a systemic nonnecrotizing granulomatous disease, the etiology of which is suspected to be immune mediated. Hematopoietic stem cell transplantation (HSCT) is effective in cases of immune diseases because of a beneficial graft-versus-autoimmune (GVA) reaction similar to the graft-versus-leukemia reaction. We report the case of a long-lasting corticosteroid-dependent sarcoidosis complicated by acute myeloid leukemia (AML) treated with allogenic HSCT. After this treatment, sarcoidosis resolved with no relapse after a long follow-up period.

Case Report

A 55-year-old woman was referred to our unit for arthritis and cutaneous eruption. She had a 2-year history of joint pain in her knees, wrists, and ankles with morning stiffness and had several episodes of anterior uveitis. Examination found metacarpophalangeal arthritis and multiple tiny infiltrated papules on her back, arms, and legs. Cutaneous biopsy found a disperse inflammatory infiltrate composed of mononuclear cells and small nonnecrotizing circumscribed granulomas with epithelioid cells in the papillary dermis. Infection was ruled out by negative results of special staining, bacterial skin culture, and negative intradermal tuberculin test. A visceral evaluation excluded hepatic and pulmonary involvement. Blood cell count, calcium levels, and plasmatic level of angiotensin-converting enzyme were within normal ranges. Based on the physical exam and laboratory findings, we diagnosed lichenoid sarcoidosis. Antimalarial medications, methotrexate, cyclines, and thalidomide were successively tried with limited improvement. Systemic corticosteroids induced remission but were associated with relapses after dose reduction. Finally, low doses of corticosteroids (7 mg/d) combined with methotrexate (15 mg/wk) helped achieve remission but these doses could not be reduced. Eight years after the diagnosis, blood investigations found pancytopenia with blastic cells in peripheral blood. Bone marrow biopsy found an excess of blasts with precursor cells increasing, trisomy 8, and loss of 17p/TP53 on cytogenetic analysis, leading to the diagnosis of primitive myelofibrosis progressing to AML. Umbilical cord blood HSCT after nonablative regimen with fludarabine (40 mg/m2) and cyclophosphamide (50 mg/kg) were given. On completion of treatment, the patient was asymptomatic, and full remission was obtained for both AML and sarcoidosis. Two months after HSCT, she presented with cutaneous graft-versus-host disease (GvHD), which was well controlled using mycophenolate mofetil and everolimus for 3 months. Five months after allogenic HSCT, all immunosuppressive drugs were stopped without any recurrence of sarcoidosis, which, after 4 years of follow-up, remains asymptomatic.

Hematopoietic stem cell transplantation for chronic inflammatory demyelinating polyradiculoneuropathy

J Neurol. 2020 Nov;267(11):3378-3391.


Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Axis Bldg, 446 East Ontario, Suite 10-1000, Chicago, IL, 60611, USA.


Objective: Determine toxicity and efficacy of autologous hematopoietic stem cell transplantation (HSCT) for patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who are dependent on intravenous immunoglobulins or plasmapheresis.

Methods: Unselected peripheral blood stem cells were re-infused on day 0 after conditioning with cyclophosphamide 200 mg/kg/intravenously (IV), rATG (thymoglobulin) 5.5 mg/kg/IV, and rituximab 1000 mg/IV.

Results: Sixty-six patients underwent HSCT for CIDP. Data on sixty patients with a mean follow-up of 4.5 years (range 2-5 years) were available for analysis. There were no treatment-related deaths, and overall survival was 97%. Post-transplant immune medication-free remission was 80%, 78%, 76% 78%, and 83% at 1, 2, 3, 4, and 5 years. Ambulation without assistance improved from 33% pre-HSCT to 82% 82%, 81%, 86%, and 83% at 1, 2, 3, 4, and 5 years, respectively. Mean right/left hand grip strength (kg) improved significantly (all p values < 0.01) from 18.1/16.5 pre-HSCT to 26.3/25.4, 29.2/28.2, 28.8/28.6, 30.3/25.5, and 30.8/29.1 at 1, 2, 3, 4, and 5 years, respectively. Average nerve conduction velocity (NCV) (m/s) improved significantly (all p values ≤ 0.001) from a mean of 27.2 pre-HSCT to 33.5, 33.8, 37.7, 38.2, and 38.3 at 1, 2, 3, 4, and 5 years, respectively. Average compound motor action potential (CMAP) (mv) improved significantly (p values ≤ 0.001) from a mean of 3.6 pre-HSCT to 4.6, 4.6, 5.0, 5.1, and 4.1 at 1, 2, 3, 4, and 5 years, respectively.

Conclusion: A randomized trial is indicated to verify these results and confirm that HSCT reverses disability and offers long-term immune therapy independence.

Chronic inflammatory demyelinating polyradiculoneuropathy: a role for haematopoietic stem cell transplantation

Autoimmunity. 2008 Dec;41(8):611-5.


Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK.


Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical syndrome of a chronic progressive or relapsing and remitting, symmetrical, sensory and motor radiculoneuropathy. The immune reaction in CIDP is characterised by selective inflammation of peripheral nerves and is probably due to the interaction of cellular and humoral responses. Only three treatments for CIDP have demonstrated benefit in randomised studies, corticosteroids, plasma exchange and intravenous immunoglobulin. 25% of patients fail to respond or do not respond adequately to these treatments. Experimental data in animal models have shown that several autoimmune disorders, either congenital or acquired, can be transferred and/or treated by the transplantation of bone marrow stem cells. Haematopoietic stem cell transplantation (HSCT) has been performed with varying success in over 700 patients with autoimmune disorders throughout Europe. The experience in CIDP is very limited. This article will review current understanding of CIDP and experience of the use of HSCT in refractory CIDP.

Advances in the diagnosis, pathogenesis and treatment of CIDP

Nat Rev Neurol. 2011 Aug 16;7(9):507-17.


Neuroimmunology Unit, Department of Pathophysiology, National University of Athens Medical School, Building 16, Room 39, 75 Mikras Asias Street, Athens 11527, Greece.


Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Despite clinical challenges in diagnosis-owing in part to the existence of disease variants, and different views on how many electrophysiological abnormalities are needed to document demyelination-consensus criteria seem to have been reached for research or clinical practice. Current standard of care involves corticosteroids, intravenous immunoglobulin (IVIg) and/or plasmapheresis, which provide short-term benefits. Maintenance therapy with IVIg can induce sustained remission, increase quality of life and prevent further axonal loss, but caution is needed to avoid overtreatment. Commonly used immunosuppressive drugs offer minimal benefit, necessitating the development of new therapies for treatment-refractory patients. Advances in our understanding of the underlying immunopathology in CIDP have identified new targets for future therapeutic efforts, including T cells, B cells, and transmigration and transduction molecules. New biomarkers and scoring systems represent emerging tools with the potential to predict therapeutic responses and identify patients with active disease for enrollment into clinical trials. This Review highlights the recent advances in diagnosing CIDP, provides an update on the immunopathology including new target antigens, and discusses current treatments, ongoing challenges and future therapeutic directions.

Successful autologous stem cell transplantation in a patient with chronic inflammatory demyelinating polyneuropathy

J Neurol Neurosurg Psychiatry. 2002 Jan;72(1):127-8.


Journal of Neurology, Neurosurgery & Psychiatry


PMID: 11784845


PMCID: PMC1737683


DOI: 10.1136/jnnp.72.1.127

Autologous Hematopoietic Stem Cell Transplantation for Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Can J Neurol Sci. 2021 Nov;48(6):760-766.


Ottawa Stem Cell Program, Canadian Blood Services, Ottawa, Canada.


Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) refractory to conventional therapy can lead to marked disability and represents a therapeutic challenge.

Objective: To report five cases of treatment-refractory disabling CIDP treated with autologous hematopoietic stem cell transplantation (AHSCT).

Methods: This was a retrospective cohort study from a tertiary care referral center for both neuromuscular disease and AHSCT. Patients with CIDP treated with AHSCT between 2008 and 2020 were included. All patients had major persistent and disabling neuropathic deficits despite combinations of intensive immunosuppressive therapy. The primary outcome measures were: Medical Research Council sum score, Overall Neuropathy Limitations Scale and requirement for ongoing CIDP immunotherapy after transplantation. We also analyzed safety outcomes by documenting all severe AHSCT-related complications.

Results: Five patients with refractory CIDP underwent AHSCT. Three were classified as manifesting a typical syndrome, two were classified as the multifocal Lewis Sumner variant. The mean age at time of CIDP diagnosis was 33.4 years (range 24-46 years), with a median delay of 46 months (range 21-135 months) between diagnosis and AHSCT. The median follow-up period was 41 months. All five patients were able to wean off CIDP-related immunotherapy. Marked improvements in Medical Research Council scale and overall Neuropathy Limitations Scale were noted in 4/5 patients. One patient with longstanding neurogenic atrophy showed no improvement in disability scales. There were no treatment-related deaths or critical illnesses.

Conclusions: AHSCT can achieve marked sustained clinical improvement of refractory CIDP and may allow for weaning off long-term complex immunotherapies.

Efficacy of hematopoietic stem cell transplantation treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy

Eur J Neurol. 2023 May 12.


Department of Neurology, Huashan Hospital Fudan University, Shanghai, China.


Background and purpose: Treatment options for chronic inflammatory demyelinating polyneuropathy (CIDP) are intravenous immunoglobulin, plasmapheresis, corticosteroids and immunosuppressive drugs. However, a substantial proportion of patients with CIDP remain refractory to treatment and develop severe functional disability. A systematic review and a meta-analysis of the efficacy of hematopoietic stem cell transplantation (HSCT) treatment in refractory CIDP patients was performed.


Methods: The study is based on queries in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and databases on 4 December 2022. Articles that met our eligibility criteria were included after screening. Patients' characteristics, treatment regime and outcome measures were extracted.


Results: Eighty-nine patients in 11 studies were included. The pooled estimate of responsiveness amongst the four included studies was 87.04% (95% confidence interval 66.7%-99.5%) and the pooled estimate of freedom of all immune modulating or suppressive drugs was 80.75% (95% confidence interval 71.2%-90.2%).


Conclusion: This meta-analysis and systematic review suggested that HSCT can be effective in the treatment of refractory CIDP. Whilst there are risks involved, HSCT may be a beneficial and viable therapy for refractory CIDP when carefully evaluated.

Autologous hematopoietic stem cell transplantation for chronic inflammatory demyelinating polyneuropathy

Rev Med Interne. 2021 Sep;42(9):639-649.


Assistance Publique-Hôpitaux de Paris, Université Paris-Saclay, service de medecine interne, groupe hospitalier universitaire Paris Sud, hôpital Bicêtre, 94275 Le Kremlin-Bicêtre cedex, France. Electronic address:


HChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a dysimmune neuropathy with sensory and/or motor symptoms due to destruction of the myelin sheat secondary to an auto-immune attack. A quarter to a third of patients do not respond to immunomodulatory first line recommended therapies. No second line treatment has shown its effectiveness with a sufficient level of evidence. Autologous hematopoietic stem cell transplantation (AHSCT) is a promising therapy for autoimmune disease, especially for CIDP in recent works. We present in this article an update on the diagnosis of CIDP, its conventional treatments as well as the results of AHSCT in this indication, which was the subject of French recommendations under the aegis of the SFGMTC and neuromuscular disease french faculty (FILNEMUS) as a third line therapy after failure of two first-line and one second-line treatments.

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