Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life

Saccardi, Riccardo; Mancardi, Gianluigi; Solari, Alessandra; Bosi, Alberto; Bruzzi, Paolo; Bartolomeo, Paolo Di; Donelli, Amedea; Filippi, Massimo; Guerrasio, Angelo; Gualandi, Francesca; Nasa, Giorgio La; Murialdo, Alessandra; Pagliai, F; Papineschi, Federico; Scappini, Barbara; Marmont, A

doi:10.1182/blood-2004-08-3205

Cited by 146 publications

(103 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our sample, we did not find a correlation between improved MRI scans and the level of neurological disability (EDSS), as opposed to the Italian group. 29 This could be explained by the reduced number of patients with lesions before transplantation: seven in the BEAM group and one in the CY/ATG group. A more formal MRI study would be needed to verify disease progression by means of lesion burden as determined by MRI brain volume, number of lesions and other markers, especially in reduced intensity regimens.…”

Section: Discussionmentioning

confidence: 99%

“…An intermediate-intensity conditioning regimen, BEAM (BCNU, cytosine arabinoside, melphalan and etoposide) is better tolerated and has a lower morbidity and mortality rate. 26,29 By contrast, a truly non-myeloablative regimen of CY and anti-lymphocyte antibodies has been used by Burt et al 30,31 for HSCT in patients with MS and has also been used safely in numerous autoimmune diseases, including systemic lupus erythematosus, 32 type I diabetes 33 and systemic sclerosis. 34 The mortality rate of HSCT for MS in studies with relatively large samples is described in Table 1.…”

Section: Introductionmentioning

confidence: 99%

“…34 The mortality rate of HSCT for MS in studies with relatively large samples is described in Table 1. [25][26][27][28][29][30][35][36][37][38][39][40][41][42][43][44][45] Although these studies use myeloablative conditioning regimens of varying intensity, non-myeloablative regimens have been advocated for autologous HSCT of autoimmune diseases. 46 Recently, one of these latter studies was published using CY/rATG and it reported no deaths among 21 patients with relapsing-remitting MS. 31 There is a controversy regarding the analysis of the immune system modifications as increases in naive CD4 þ T cells over memory cells 20 and the fact that more intensive regimens seem to present better results than less intensive regimens.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

Hamerschlak

Rodrigues

Moraes

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/ rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intratransplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P ¼ 0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for a ll patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P ¼ 0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term followup would be required to fully assess the differences in therapeutic effectiveness between the two regimens.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

Hamerschlak

Rodrigues

Moraes

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…Among patients having relapses until the time of HSCT, more than 85 % who received a conditioning regimen of BEAM plus ATG were free from clinical relapses in the absence of ongoing treatment with other disease-modifying agents [50,51]. Similarly, gadolinium-enhancing CNS lesions or new lesions on serial magnetic resonance imaging were uncommon [52,53]. Although randomized comparisons of different intensity conditioning regimens have not been performed, within the limitations of available information, it appears that dose-intensity influences the control of CNS inflammation.…”

Section: Lesson 4: Hsct Is More Likely To Be Effective For Ms Patientmentioning

confidence: 99%

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

Atkins

Freedman

2013

Neurotherapeutics

View full text Add to dashboard Cite

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...

show abstract

“…9 From our report, the question arises whether such transplant procedure may also be beneficial for MS patients affected by t-AML after topoisomerase II treatment. …”

mentioning

confidence: 99%

Two new cases of acute promyelocytic leukemia following mitoxantrone treatment in patients with multiple sclerosis

et al. 2006

View full text Add to dashboard Cite

Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life

Cited by 146 publications

References 35 publications

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

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

Two new cases of acute promyelocytic leukemia following mitoxantrone treatment in patients with multiple sclerosis

Contact Info

Product

Resources

About