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From ECTRIMS 2011: Early versus late/salvage autologous haematopoietic stem cell transplantation in multiple sclerosis patients
A.A. Novik, A.N. Kuznetsov, B.V. Afanasiev, I.A. Lisukov, V.A. Rossiev, O.A. Rykavicin, V.Y. Melnichenko, D.A. Fedorenko, G.N. Gridasov, T.I. Ionova, A.D. Kulagin, K.A. Kurbatova, S.V. Makarov, N.E. Osipova, S.V. Shamansky, G.V. Gorodokin (Moscow, St. Petersburg, Novosibirsk, Samara, RU; New Jersey, US)
During the last decade high-dose immunosuppressive therapy (HDIT) with autologous haematopoietic stem cell transplantation (AHSCT) has been used with increasing frequency as a therapeutic option for MS patients. At the same time the patient selection criteria for HDIT+AHSCT are still unclear. We aimed to study treatment outcomes in MS patients after early vs late/salvage HDIT+AHSCT.
186 patients with MS (secondary progressive – 79 patients, primary progressive – 28, progressive-relapsing – 5 and relapsing-remitting – 74) from 6 clinical centers were included in this study. Median EDSS at base-line was 4.5 (range 1.5 – 8.5). 67 patients underwent early AHSCT (EDSS 1.5-3.0); 119 - late/salvage AHSCT (EDSS 3.5-8.5). The median follow-up duration was 34 months (range 1.5 – 143).
In the vast majority of cases the mobilization and transplantation procedures were well tolerated. One case of death on day +8 from sepsis with multiple organ failure was registered. The efficacy analysis at 12 months posttransplant was performed in 142 patients. In the group after early AHSCT (46 patients) neurological improvement was observed in 19 (41%), stabilization – in 26 (57%) patients; 1 (2%) patient progressed. In the group after late/salvage AHSCT (96 patients) neurological improvement was observed in 42 patients, stabilization – in 42 patients; 12 patients progressed. At long-term follow-up in the group after early AHSCT (median follow-up duration - 38 months) overall clinical response (neurological improvement or stabilization) was registered in 35 patients. 4 patients progressed at different time-points after AHSCT. Among 78 patients after late/salvage AHSCT overall long-term clinical response (median follow-up duration - 41 months) was observed in 52 patients. 26 patients progressed at different time-points after AHSCT. One patient died after disease progression at 3 years posttransplant.
The estimated 5-year progression-free rates were 87% (95% CI, 68% to 96%) in early AHSCT group and 70% (95% CI, 54% to 81%) in late/salvage AHSCT group. Statistically significant difference between the progression-free survival probabilities in two groups was determined (log-rank test, P=0.02, 95% CI).
This study provides ample evidence in support of HDCT+AHSCT efficacy in MS patients. The results obtained show that treatment outcomes are significantly better in patients undergoing transplantation at early stages of the disease. Further studies are worthwhile to better indentify timing for HDCT+AHSCT in MS patients.
A.A. Novik, A.N. Kuznetsov, B.V. Afanasiev, I.A. Lisukov, V.A. Rossiev, O.A. Rykavicin, V.Y. Melnichenko, D.A. Fedorenko, G.N. Gridasov, T.I. Ionova, A.D. Kulagin, K.A. Kurbatova, S.V. Makarov, N.E. Osipova, S.V. Shamansky, G.V. Gorodokin (Moscow, St. Petersburg, Novosibirsk, Samara, RU; New Jersey, US)
During the last decade high-dose immunosuppressive therapy (HDIT) with autologous haematopoietic stem cell transplantation (AHSCT) has been used with increasing frequency as a therapeutic option for MS patients. At the same time the patient selection criteria for HDIT+AHSCT are still unclear. We aimed to study treatment outcomes in MS patients after early vs late/salvage HDIT+AHSCT.
186 patients with MS (secondary progressive – 79 patients, primary progressive – 28, progressive-relapsing – 5 and relapsing-remitting – 74) from 6 clinical centers were included in this study. Median EDSS at base-line was 4.5 (range 1.5 – 8.5). 67 patients underwent early AHSCT (EDSS 1.5-3.0); 119 - late/salvage AHSCT (EDSS 3.5-8.5). The median follow-up duration was 34 months (range 1.5 – 143).
In the vast majority of cases the mobilization and transplantation procedures were well tolerated. One case of death on day +8 from sepsis with multiple organ failure was registered. The efficacy analysis at 12 months posttransplant was performed in 142 patients. In the group after early AHSCT (46 patients) neurological improvement was observed in 19 (41%), stabilization – in 26 (57%) patients; 1 (2%) patient progressed. In the group after late/salvage AHSCT (96 patients) neurological improvement was observed in 42 patients, stabilization – in 42 patients; 12 patients progressed. At long-term follow-up in the group after early AHSCT (median follow-up duration - 38 months) overall clinical response (neurological improvement or stabilization) was registered in 35 patients. 4 patients progressed at different time-points after AHSCT. Among 78 patients after late/salvage AHSCT overall long-term clinical response (median follow-up duration - 41 months) was observed in 52 patients. 26 patients progressed at different time-points after AHSCT. One patient died after disease progression at 3 years posttransplant.
The estimated 5-year progression-free rates were 87% (95% CI, 68% to 96%) in early AHSCT group and 70% (95% CI, 54% to 81%) in late/salvage AHSCT group. Statistically significant difference between the progression-free survival probabilities in two groups was determined (log-rank test, P=0.02, 95% CI).
This study provides ample evidence in support of HDCT+AHSCT efficacy in MS patients. The results obtained show that treatment outcomes are significantly better in patients undergoing transplantation at early stages of the disease. Further studies are worthwhile to better indentify timing for HDCT+AHSCT in MS patients.