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

Farge, Dominique; Labopin, Myriam; Tyndall, Alan; Fassas, Αthanasios; Mancardi, Gianluigi; Laar, Jaap van; Ouyang, Jian; Kozák, Tomáš; Moore, John J.; Kötter, Ina; Chesnel, Virginie; Marmont, A; Gratwohl, Aloïs; Saccardi, Riccardo

doi:10.3324/haematol.2009.013458

Cited by 328 publications

(312 citation statements)

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“…Approximately 45 % of patients have a stable EDSS score at 5 to 7 years after HSCT [21,51,54]. Although the accumulated outcome data of HSCT for MS is largely from cohort studies that lack a randomized control group, most of the patients selected for HSCT had ongoing progression and had previously exhausted all other therapeutic options.…”

Section: Lesson 6: Hsct Can Results In Long-term Progression-free Outcmentioning

confidence: 99%

“…There is a large worldwide experience using autologous HSCT for MS [9,21], however, only a few transplants have been performed using human leukocyte antigen (HLA) matched allogeneic or donorderived HSC grafts. More than 95 % of recipients of autologous HSC have received grafts collected by peripheral vein leukopheresis.…”

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confidence: 99%

“…Thus, experience with total body irradiation is limited to less than 100 MS patients. There are regional differences in the use of total body irradiation; 30 % of patients undergoing HSCT for an autoimmune disease reported to the CIBMTR [9] whereas less than 5 % of patients reported to the EBMT registry [21] received total body irradiation.…”

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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 6: Hsct Can Results In Long-term Progression-free Outcmentioning

confidence: 99%

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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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“…There was a reduction in the incidence of SAEs during the course of the trial (data not shown) implying that centres became more proficient at managing HSCT with experience. 29 It is relevant to note that patients in both groups received 4g/m 2 cyclophosphamide at mobilisation.…”

Section: Discussionmentioning

confidence: 99%

Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial

Lindsay

Allez

Clark

et al. 2017

The Lancet Gastroenterology & Hepatology

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BACKGROUND The randomised controlled ASTIC trial showed no benefit of mobilisation and autologous haematopoietic stem-cell transplantation (HSCT) compared with mobilisation followed by conventional therapy using a stringent primary endpoint (steroid-free clinical remission for 3 months with no endoscopic or radiological evidence of intestinal inflammation) in patients with treatment-refractory Crohn's disease. We now assess HSCT in patients enrolled in the ASTIC trial using endpoints that are traditional for clinical trials in Crohn's disease, and identify factors that predict benefit or harm. METHODS Patients who underwent mobilisation and were randomly assigned to conventional therapy in the ASTIC trial were offered HSCT at 1 year and underwent complete assessment for a further year. We report analyses of the combined cohort of patients who underwent HSCT at any time during the ASTIC trial programme. The primary outcome for this analysis was 3-month steroid-free clinical remission at 1 year after HSCT (Crohn's Disease Activity Index [CDAI] <150). We also examined the degree of endoscopic healing at 1 year. Multivariate analysis was performed to identify factors associated with achieving the primary endpoint by using logistic regression, and factors associated with experiencing a serious adverse event using Poisson regression. Participants were not masked to treatment, but the adjudication panel that reviewed radiology and endoscopy was masked to allocation and visits. All patients who underwent HSCT and had data available at baseline and 1-year follow-up were included in the primary and safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00297193. FINDINGS Between June 28, 2007, and Sept 1, 2011, 45 patients were enrolled in the ASTIC trial from 11 European transplant units. 23 patients were randomly assigned to immediate HSCT, and 22 patients were assigned to mobilisation followed by conventional care. After completion of the ASTIC trial, 17 patients from the conventional care group received HSCT. In the combined cohort, data were available for 40 patients at baseline and 38 patients at 1 year after HSCT (one patient died, one withdrew). At 1 year after HSCT, 3-month steroid-free clinical remission was seen in 13 (38%, 95% CI 22-55) of 34 patients with available data for the whole year. Complete endoscopic healting was noted in 19 (50%, 34-66) of 38 patients. On multivariate analyses, factors associated with the primary outcome were short disease duration (odds ratio [OR] 0·64, 95% CI 0·41-0·997 per year; p=0·048) and low baseline CDAI (0·82, 0·74-0·98 per 10 units; p=0·031). 76 serious adverse events occurred in 23 of 40 patients with available data. The most common serious adverse event was infection, most of which were treatment related. Smoking and perianal disease at baseline were independent factors associated with the number of serious adverse events (OR 3·07 [95% CI 1·75-5·38; p=0·0001] for smoking and 3·97 [2·17-7·25; p<0·0001] for perianal disease) on multivariate...

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“…Autologous transplant-related mortality is approximately 3-5% for patients with myeloma and lymphoma and approximately 5-10% for those with scleroderma (23, 27, 30, 31). Transplant is an intensive procedure with significant side effects including nausea, vomiting, diarrhea and oral mucositis which usually resolve with blood count recovery.…”

Section: The Process Of Autologous Hsctmentioning

confidence: 99%