Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience

Mancardi, G. L.; Sormani, MP; Gioia, Massimo Di; Vuolo, Luisa; Gualandi, Francesca; Amato, Maria Pia; Capello, Elisabetta; Currò, Daniela; Uccelli, Antonio; Bertolotto, Antonio; Gasperini, Claudio; Lugaresi, Alessandra; Merelli, E.; Meucci, G.; Motti, L.; Mr, Tola; Scarpini, Elio; Repice, Annamaria; Massacesi, Luca; Saccardi, Riccardo; Donnini, Irene; Bosi, Alberto; Guidi, Stefano; Bagigalupo, A; Bonzano, Laura; Bruzzi, Paolo; Roccatagliata, Luca; Falcón-Antenucci, Rosse Mary; Granella, Franco; Martino, Gianvito; Rottoli, M. R.; Solaro, Claudio; Salvi, Flavia; Barilaro, Alessandro; Capobianco, Marco

doi:10.1177/1352458511429320

Cited by 122 publications

(125 citation statements)

References 30 publications

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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%

“…A reduction in EDSS occurred in 27 % of HSCT recipients with more than 7 years of follow-up in an Italian cohort study [51]. However, in this instance, the improvements were sustained, but this has not always been the case.…”

Section: Lesson 7: the Recovery Of Functional Ability Can Occur In Hsmentioning

confidence: 93%

“…The use of higher intensity conditioning regimens, such as BEAM with ATG or busulphan/cyclophosphamide with ATG, is effective at suppressing episodic CNS inflammation. 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].…”

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

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%

Section: Lesson 7: the Recovery Of Functional Ability Can Occur In Hsmentioning

confidence: 93%

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

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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“…The conditioning regimens with the strongest traction within each intensity category are cyclophosphamide and ATG (low intensity), BEAM and ATG (intermediate intensity) and cyclophosphamide, busulfan and ATG (high intensity). In the absence of evidence from randomized comparisons, we endorse the preferential use of BEAM and ATG -the scheme that is specifically recommended for the treatment of MS in the EBMT guidelines 56 -by virtue of its extensive track record that indicates good safety and high efficacy 14,73 , and of the opportunity it provides for comparisons across data sets.…”

Section: [H3] Conditioning Regimenmentioning

confidence: 99%

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

et al. 2017

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Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ~20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4–5 years in 70–80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs

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“…From the above reasons treatment responses to aHSCT have been less clear in SPMS patients, and the fraction of patients, who show sustained improvement for more than 1 EDSS point is much larger in RRMS patients [8]. There is currently no doubt that aHSCT is most effective in highly active RRMS patients.…”

Section: Patient Eligibility Criteria -Who Is a Candidate?mentioning

confidence: 99%

Autologous Hematopoietic Stem Cell Transplantation as a Treatment Option for Aggressive Multiple Sclerosis

Pfender

Saccardi

Martin

2013

Curr Treat Options Neurol

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OPINION STATEMENT: Despite the development of several injectable or oral treatments for relapsing-remitting multiple sclerosis (RRMS), it remains difficult to treat patients with aggressive disease, and many of these continue to develop severe disability. During the last two decades autologous hematopoietic stem cell transplantation (aHSCT) has been explored with the goal to eliminate an aberrant immune system and then re-install a healthy and tolerant one from hematopoietic precursor cells that had been harvested from the patient prior to chemotherapy. Clinical studies have shown that aHSCT is able to completely halt disease activity in the majority of patients with aggressive RRMS. Research on the mechanisms of action supports that aHSCT indeed leads to renewal of a healthy immune system. Below we will summarize important aspects of aHSCT and mention the currently best-examined regimen. AbstractDespite the development of several injectable or oral treatments for relapsingremitting multiple sclerosis (RRMS), it remains difficult to treat patients with aggressive disease, and many of these continue to develop severe disability. During the last two decades autologous hematopoietic stem cell transplantation (aHSCT) has been explored with the goal to eliminate an aberrant immune system and then re-install a healthy and tolerant one from hematopoietic precursor cells that had been harvested from the patient prior to chemotherapy. Clinical studies have shown that aHSCT is able to completely halt disease activity in the majority of patients with aggressive RRMS. Research on the mechanisms of action supports that aHSCT indeed leads to renewal of a healthy immune system. Below we will summarize important aspects of aHSCT and mention the currently best-examined regimen.

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Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience

Cited by 122 publications

References 30 publications

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

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

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

Autologous Hematopoietic Stem Cell Transplantation as a Treatment Option for Aggressive Multiple Sclerosis

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