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Clinical experience in autologous hematopoietic stem cell transplantation in refractory aggressive multiple sclerosis
C Alcalá1, F Pérez-Miralles1, I Boscá1, F Gascón2, A Navarré2, M Escutia1, A Bernad2, J de la Rubia3, F Coret2, B Casanova1
1Hospital Universitari i Politècnic La Fe, MS Unit - Neurology Department, Valencia, Spain, 2Hospital Clínico Universitario, Unit of Neuroimmunology - Neurology Department, Valencia, Spain, 3Hospital Universitari i Politècnic La Fe, Hematology, Valencia, Spain
Background: Despite treatment with current first and second-line therapies, some MS patients suffer a breakthrough form, reaching significant disability in the early stages. Autologous bone marrow transplantation (BMT) is used as a compassionate treatment for aggressive and refractory MS.
Objectives: To describe the clinical experience of a series of refractory patients with aggressive multiple sclerosis subject in which a BMT was performed at some point in their evolution.
Methods: This is a descriptive study about the case mix of relapsing-remitting (RRMS) or secondary progressive MS with relapses (SPMS) in which a BMT was performed from 2 tertiary referral hospitals in Valencia (Spain) from February 1999 to March 2014. Presence of attacks, the Expanded Disability Status Scale (EDSS) and presence of adverse events were quarterly assessed.
Results: Twenty-seven patients underwent BMT (19 women, mean age at diagnosis of 27.1 [SD 7.7]), 16 RRMS (72%) and 11 SPMS (44%). Mean evolution time from first attack to BMT was 8.4 years (SD 4.0), and the median of previous treatments was 3 (range 1-6). The annualized relapse rate (ARR) the year before BMT was 1.2 (SD 0.82), and the median EDSS was 4.5 (range 2-7). Most patients (63%) have been followed for a period of time ≥4 years. No patients have required disease-modifying therapies during the first 4 years after BMT, only 7 patients started other therapies after a mean of 4.3 (SD 2.8) years. ARR decreased significantly at 2 (mean 0.13 [SD 0.22], p=0.001) and 4 (mean 0.20 [SD 0.36], p=0.002) years of follow-up. Most RRMS patients (83.3%) remained free from sustained-progression at the end of follow up period compared with 28.6% of SPMS patients (p=0.044). Sustained improvement was observed in 11 patients (44%), 10 RRMS patients. K-M curves showed differences in favour of patients with RRMS (median time 48 months [SE 11.5]) compared to SPMS (p = 0.039). Sixteen patients had immediate adverse reactions to BMT, 2 of them serious; 3 patients developed neoplasms (1 carcinoma in situ of the cervix, 2 breast cancers), with median time to diagnosis of 4.9 years (SD 0.6).
Conclusions: BMT is an effective alternative treatment for aggressive and refractory RRMS patients. Improvement of long-time disability has been observed in this subgroup of patients. There is no evidence of modification of clinical course in SPMS patients. Most patients have suffered short-term toxicity, but without long-term disability or mortality.
C Alcalá1, F Pérez-Miralles1, I Boscá1, F Gascón2, A Navarré2, M Escutia1, A Bernad2, J de la Rubia3, F Coret2, B Casanova1
1Hospital Universitari i Politècnic La Fe, MS Unit - Neurology Department, Valencia, Spain, 2Hospital Clínico Universitario, Unit of Neuroimmunology - Neurology Department, Valencia, Spain, 3Hospital Universitari i Politècnic La Fe, Hematology, Valencia, Spain
Background: Despite treatment with current first and second-line therapies, some MS patients suffer a breakthrough form, reaching significant disability in the early stages. Autologous bone marrow transplantation (BMT) is used as a compassionate treatment for aggressive and refractory MS.
Objectives: To describe the clinical experience of a series of refractory patients with aggressive multiple sclerosis subject in which a BMT was performed at some point in their evolution.
Methods: This is a descriptive study about the case mix of relapsing-remitting (RRMS) or secondary progressive MS with relapses (SPMS) in which a BMT was performed from 2 tertiary referral hospitals in Valencia (Spain) from February 1999 to March 2014. Presence of attacks, the Expanded Disability Status Scale (EDSS) and presence of adverse events were quarterly assessed.
Results: Twenty-seven patients underwent BMT (19 women, mean age at diagnosis of 27.1 [SD 7.7]), 16 RRMS (72%) and 11 SPMS (44%). Mean evolution time from first attack to BMT was 8.4 years (SD 4.0), and the median of previous treatments was 3 (range 1-6). The annualized relapse rate (ARR) the year before BMT was 1.2 (SD 0.82), and the median EDSS was 4.5 (range 2-7). Most patients (63%) have been followed for a period of time ≥4 years. No patients have required disease-modifying therapies during the first 4 years after BMT, only 7 patients started other therapies after a mean of 4.3 (SD 2.8) years. ARR decreased significantly at 2 (mean 0.13 [SD 0.22], p=0.001) and 4 (mean 0.20 [SD 0.36], p=0.002) years of follow-up. Most RRMS patients (83.3%) remained free from sustained-progression at the end of follow up period compared with 28.6% of SPMS patients (p=0.044). Sustained improvement was observed in 11 patients (44%), 10 RRMS patients. K-M curves showed differences in favour of patients with RRMS (median time 48 months [SE 11.5]) compared to SPMS (p = 0.039). Sixteen patients had immediate adverse reactions to BMT, 2 of them serious; 3 patients developed neoplasms (1 carcinoma in situ of the cervix, 2 breast cancers), with median time to diagnosis of 4.9 years (SD 0.6).
Conclusions: BMT is an effective alternative treatment for aggressive and refractory RRMS patients. Improvement of long-time disability has been observed in this subgroup of patients. There is no evidence of modification of clinical course in SPMS patients. Most patients have suffered short-term toxicity, but without long-term disability or mortality.