Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis

Burt, Richard K.; Balabanov, Roumen; Burman, Joachim; Sharrack, Basil; Snowden, John A.; Oliveira, Maria Carolina; Fagius, Jan; Rose, John; Nelson, Flavia; Barreira, Amilton Antunes; Carlson, Kristina; Han, Xiaoqiang; Moraes, Daniela A.; Morgan, Amy; Quigley, Kathleen; Yaung, Kimberly; Buckley, Regan; Alldredge, Carri; Clendenan, Allison; Calvario, Michelle A.; Henry, Jacquelyn; Jovanovic, Borko; Helenowski, Irene

doi:10.1001/jama.2018.18743

Cited by 225 publications

(278 citation statements)

References 26 publications

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“…The main differences between protocols relate to the conditioning agents and their doses, which correspondingly impact both the degree of immunoablation and myeloablation as well as toxicity 1 . While the Canadian protocol involved busulfan, high doses of cyclophosphamide and antithymocyte globulin (ATG) for conditioning, other regimens use a less toxic regimen of lower‐dose cyclophosphamide and ATG, and no busulfan whatsoever 34,35 . Although the toxicity profile of busulfan for IAHSCT in MS 3 has been optimized through improved patient selection, lower dosages, and IV administration, this alkylating agent is known to cause neurotoxicity at higher doses 36 .…”

Section: Discussionmentioning

confidence: 99%

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Thebault

Lee

Bose

et al. 2020

Ann Clin Transl Neurol

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Objective: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. Methods: Sera were collected from 22 MS patients pre-and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. Results: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). Interpretation: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

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Section: Discussionmentioning

confidence: 99%

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Thebault

Lee

Bose

et al. 2020

Ann Clin Transl Neurol

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“…HSCT has been used for hematological malignancies since the 1950s and offers the advantage of being a one‐time procedure. It has previously been reported that treatment with HSCT for RRMS leads to improvement in disability and sustained disease remission for up to 5 years . It is at present unknown if these results can be generalized to 10 years and beyond.…”

Section: Introductionmentioning

confidence: 96%

Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation

et al. 2019

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Objectives:To determine whether treatment with autologous hematopoietic stem cell transplantation (HSCT) can induce sustained complete remission in patients with multiple sclerosis (MS). Material and methods:Case series of patients with relapsing-remitting MS (n = 10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n = 9) or a cyclophosphamide/ATG conditioning regimen (n = 1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as "no evidence of disease activity-4," sustained for a period of at least 5 years without any ongoing disease-modifying treatment. Furthermore, MS was considered as "resolved" if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well.Results: Five out of 10 patients were in sustained complete remission at the end of the study. In three of them, MS was resolved. Conclusions:Our data demonstrate that sustained complete remission after autologous HSCT for MS is possible. K E Y W O R D S cerebrospinal fluid, hematopoietic stem cell transplantation, magnetic resonance imaging, multiple sclerosis | 321 TOLF eT aL.

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“…The proportion of patients with no disease activity was 98.1% at 1 year, 90.3% at 3 years, and 78.5% at 5 years in the haematopoietic stem cell transplantation group. These ratios were 20.8%, 5.93%, and 2.97% respectively for the DMT group . Because of severe side effects, haematopoietic stem cells may be an alternative for severe pedMS.…”

Section: Multiphasic Diseasementioning

confidence: 94%

“…These ratios were 20.8%, 5.93%, and 2.97% respectively for the DMT group. 25 Because of severe side effects, haematopoietic stem cells may be an alternative for severe pedMS.…”

Section: Autologous Haematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Treatment in childhood central nervous system demyelinating disorders

Konuşkan

Anlar

2019

Develop Med Child Neuro

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The last two decades witnessed significant advances in the treatment of acquired demyelinating disorders: thirteen new agents have been approved for the treatment of multiple sclerosis in adults by the European Medicines Agency and US Food and Drug Administration in the last twenty years. Although the long‐term efficacy and safety profiles of some new drugs are still being assessed in paediatric MS, clinicians may have to use them in the management of paediatric onset MS resistant to first‐line medications, based on results obtained in adult‐onset disease. This review summarizes the current approach to treatment in children with demyelinating syndromes. What this paper adds Serological markers affect management in paediatric demyelinating diseases. Antibodies against aquaporin‐4 and myelin oligodendrocyte glycoprotein should be tested in children with acute demyelinating disease. New therapeutic agents currently in trial for pediatric disease should be used with close follow‐up.

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Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis

Cited by 225 publications

References 26 publications

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis

Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation

Treatment in childhood central nervous system demyelinating disorders

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