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Hematopoietic Stem Cell Implantation Prevents Disability Worsening in Patients With MS

While patients with relapsing-remitting MS were found to benefit more from aHSCT, patients with progressive MS still experienced stability in disability scores.

Data from a recent study published in Neurology suggest that autologous hematopoietic stem cell transplantation (aHSCT) prevented disability worsening in the majority of patients evaluated with multiple sclerosis (MS) and produced a long-term disability improvement in patients with relapsing-remitting MS (RRMS). 

The observational, retrospective, multicenter cohort study found that the disability worsening-free survival rate was 85.5% (95% CI, 76.9-94.1) at 5 years and 71.3% (95% CI, 57.8-84.4) at 10 years in patients with RRMS. The disability worsening-free survival rate was 71.0% (95% CI, 59.4-82.6) at 5 years and 57.2% (95% CI, 41.8-72.7) at 10 years in patients with progressive MS. 

“Our data extend previous studies at 5 years demonstrating that the effects of aHSCT persist for over a decade. These results are of particular relevance considering that patients treated with aHSCT were affected by extremely aggressive forms of MS, which is not the case in available randomized clinical trials,” wrote the study authors, among which was Matilde Inglese, MD, PhD, associate professor of neurology, radiology, and neuroscience, Icahn School of Medicine, Mount Sinai.

“Of note, the 5-years progression-free survival rate in our cohort of RRMS (85.5%) is higher than those reported with other highly active treatments for MS, such as natalizumab and alemtuzumab. In line with previous observations, disability worsening-free survival in our cohort was higher in RRMS patients with lower treatment exposure, confirming the notion that aHSCT should be performed early in the course of the disease,” they added.

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Inglese and colleagues analyzed data from 210 patients that underwent aHSCT in Italy from 1997-2019, 122 (58%) of which had RRMS. The patients had a median baseline expanded disability severity scale (EDSS) score of 6 (range, 1-9) and a mean follow-up time of 6.2 years (standard deviation [SD], 5) after treatment.

The authors found that patients with RRMS that had a higher treatment exposure prior to aHSCT were more likely to experience disability worsening (hazard ratio [HR], 1.57; [95% CI, 1.12-2.20]; P = .009). Patients with progressive MS that had a higher number of relapses in the year prior to aHSCT were less likely to experience disability worsening (HR, 0.56; [95% CI, 0.34-0.92]; P = .022).

Inglese and colleagues also found that EDSS significantly reduced after aHSCT in RRMS patients, with a mean EDSS change of –0.09 per year (95% CI, –0.15 to –0.04; P = .001). EDSS stabilized in patients with progressive MS. A mean EDSS change of 0.02 per year was seen, but this change was not significant (95%, –0.03 to 0.07; P = .42).

Further analysis revealed that the relapse-free survival rate was 78.1% (95% CI, 68.5-87.7) at 5 years at 63.5% (95% CI, 49.4-77.6) at 10 years in patients with RRMS. When treated with the BEAM+ATG protocol, rates increased to 86.4% (95% CI, 75.8-97.0) at 5 years and 77.0% (95% CI, 61.5-92.5) at 10 years. BEAM+ATG use (HR, 0.21; [95% CI, 0.09-0.49]; P <.0001) and older age at transplant (HR, 0.94; [95% CI, 0.88-0.99]; P = .034) each independently associated with a reduced risk of relapses. 

Relapse-free survival was 88.3% (95% CI, 80.7-96.0) at 5 years and 78.9% (95% CI, 63.4-91.4) at 10 years in patients with progressive MS. BEAM+ATG use was associated with a reduced risk of relapse in this population as well (HR, 0.25; [95% CI, 0.71-0.86]; P = .029).

Inglese and colleagues found that use of the BEAM+ATG conditioning protocol was independently associated with a higher probability of maintaining no evidence of disease activity (NEDA-3) status in RRMS patients (HR, 0.27; [95% CI, 0.14-0.50]; P <.001). No characteristics were found to be associated with no evidence of disease activity (NEDA-3) status in patients with progressive MS. 

Overall, the researchers found that in patients with RRMS, the use of BEAM+ATG was associated with a lower risk of relapse (HR, 0.12 [; 95% CI, 0.05-0.32]; P <.001), MRI inflammatory activity (HR, 0.18; [95% CI, 0.07-0.48]; P = .001) and with a higher probability of maintaining NEDA-3 status (HR, 0.18; [95% CI, 0.09-0.38]; P <.001) when compared to cyclophosphamide-based protocols alone.

Three (1.4%) patient deaths occurred within 100 days after aHSCT and no deaths occurred in patients treated with aHSCT after 2007. Deaths were due to pulmonary thrombo-embolism, engraftment failure, and a Wernicke’s like encephalopathy.

“Findings from this study demonstrate that the benefits of aHSCT persist for over 10 years. Although patients with RRMS are those who benefit the most from transplant, aHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS... We suggest that aHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” Inglese and colleagues concluded.

Boffa G, Massacessi L, Inglese M, et al. Long-term clinical outcomes of hematopoietic stem cell transplantation in multiple sclerosis. Neurology. Published online January 20, 2021. doi: 10.1212/WNL.0000000000011461