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STUDY: Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation

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  • STUDY: Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation

    Don't be deflated by the under 50% success ratio. With nearly 80% of those studied having SPMS, those numbers are impressive. - Dave

    JAMA Neurology
    Original Investigation
    February*20, 2017

    Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis

    Paolo A.*Muraro,*MD1; Marcelo*Pasquini,*MD2; Harold L.*Atkins,*MD3; et al
    James D.*Bowen,*MD4; Dominique*Farge,*MD5; Athanasios*Fassas,*MD6; Mark S.*Freedman,*MD7; George E.*Georges,*MD8; Francesca*Gualandi,*MD9; Nelson*Hamerschlak,*MD10; Eva*Havrdova,*MD11; Vassilios K.*Kimiskidis,*MD12; Tomas*Kozak,*MD13; Giovanni L.*Mancardi,*MD14; Luca*Massacesi,*MD15; Daniela A.*Moraes,*MD16; Richard A.*Nash,*MD17; Steven*Pavletic,*MD18; Jian*Ouyang,*MD19; Montserrat*Rovira,*MD20; Albert*Saiz,*MD21; Belinda*Simoes,*MD16; Marek*Trněnę,*MD22; Lin*Zhu,*MD23; Manuela*Badoglio,*MSc24; Xiaobo*Zhong,*MS2; Maria Pia*Sormani,*PhD25; Riccardo*Saccardi,*MD26; for the Multiple Sclerosis–Autologous Hematopoietic Stem Cell Transplantation (MS-AHSCT) Long-term Outcomes Study Group
    Author Affiliations Article Information
    JAMA Neurol. Published online February 20, 2017. doi:10.1001/jamaneurol.2016.5867

    Key Points

    What are the long-term outcomes after autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis?

    In this multicenter cohort study of 281 patients with predominantly progressive forms of multiple sclerosis who underwent autologous hematopoietic stem cell transplant between 1995 and 2006, transplant-related mortality was 2.8% within 100 days of transplant, and neurological progression-free survival was 46% at 5 years. Younger age, relapsing form of multiple sclerosis, fewer prior immunotherapies, and lower neurological disability score were significantly associated with better outcomes.

    The results support the rationale for further randomized clinical trials of autologous hematopoietic stem cell transplantation for the treatment of multiple sclerosis.

    Importance* Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies.

    To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.

    Design, Setting, and Participants*
    Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.

    Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen.

    Main Outcomes and Measures*
    The primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models.

    Valid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95).

    Conclusions and Relevance*
    In this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results support the rationale for further randomized clinical trials of AHSCT for the treatment of MS.


    Dave Bexfield

  • #2
    The numbers rise for better suited patients....

    However, neurological outcomes in our study were considerably better in patients with relapsing MS than in those with progressive MS, consistent with recent evidence of good efficacy in relapsing-remitting MS.7,11 Using multivariate analysis, we identified relapsing MS as a factor robustly associated with progression-free survival (HR, 2.33), which remained greater than 70% at 5 years after AHSCT in this patient subgroup. In total, 81.4% of the patients in the work of Burt et al11 had relapsing-remitting MS, and progression-free survival was 87% at 4 years. In the Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) trial,7 all patients had relapsing-remitting MS by the inclusion criteria, and progression-free survival was 90.9% at 3 years.
    Dave Bexfield


    • #3
      Bart's MS Blog looked into HSCT with progressive MS as well. Here is their take:

      If you cared to read the paper by ProfG and others members of TeamG on length dependent axonopathy (we hope that it will be open access soon) it suggests that it is not too late to benefit people with progressive MS, even with immunosupression.*....


      Dave Bexfield


      • #4
        I'm bumping this up as this study features many with progressive MS. The rate is 46%, but that includes RRMSers. The true rate of remission for progressive MS is likely in the 30s, and even lower for PPMS. Not terrible, but enough to give pause for anyone risking life and savings for this treatment.

        Also, note that some HSCT protocols have changed, making it safer (no radiation, no high-dose chemo!). But safer also means less effective, especially among those with progressive disease. Some early HSCT pioneers like Sandi Selvi got the full monty. Her SPMS was stopped, but her type of transplant is no longer being done for safety reasons. So the true success numbers for secondary progressive MS performed today may be even lower.

        Jump into such a serious treatment with eyes wide open, folks.
        Dave Bexfield