Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: A MRI-based clinical study

Abstract

A low-intensity conditioning regimen with AHSCT has a profound effect on MRI inflammation and relapses, but is not able to completely abrogate MRI activity and disease progression of aggressive RRMS.

Autologous hematopoietic cell transplantation in multiple sclerosis

“…This treatment appears to be able to completely prevent recurrence of clinical relapses and MRI disease activity [20], halt disease progression, and improve disability scores in a significant number of patients [30]. Improvement in NEDA rates seen with the use of AHCT when compared to other disease-modifying therapies is striking (see Tables 2 and 3).…”

“…Although some series have reported no TRM, retrospective multi-center EBMT studies have been associated with a 100-day mortality of 1.3% [53] and high-intensity BuCy regimen used by Canadian investigators was associated with higher levels of toxicity [20]. Therefore, AHCT should be reserved for patients who have very active disease which has failed to respond to standard DMTs.…”

“…Conditioning regimens still vary between treatment centers with no standardized regimen adopted as yet. As the intensity of a regimen increases so does the risk of side effects and potential TRM [20]. The counter argument to lower intensity regimens is that they are less effective in suppressing disease activity, resulting in increased rates of relapse and disease progression [21].…”

“…A recent study has shown that using a conditioning regimen of busulfan, cyclophosphamide, and rabbit ATG (BuCy) with CD34+ cell selection caused complete suppression of disease with no relapses for up to 5 years post-transplant in all patients [20]. However, there was additional toxicity with this regimen, especially hepatic veno-occlusive disease, a serious complication associated with busulfan treatment, which was associated with one treatment-related mortality (TRM) out of the 24 patients studied.…”

Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis

“…Low intensity conditioning regimen are almost immunoablative and therefore could appear to be more appropriate in an autoimmune setting. Low intensity regimens are likely to have a better safety profile although relapses after the procedure occurs in almost 25% of treated cases 16 and MRI activity is not completely eradicated 17 which is the case with high and intermediate intensity protocols. After the conditioning regimen, the cryopreserved graft is thawed and cells infused through a central venous catheter.…”