Abstract

Background. Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder of the adult life, characterized by the progressive loss of cortical and spinal motor neurons and an outcome usually fatal within 3 to 5 yrs, due to respiratory failure, with no effective therapies presently available. Efforts are needed in ALS to find novel treatments, able to reduce or block neuronal loss and/or to rebuild damaged neuronal circuits. Recent studies have raised the interest for the use of bone marrow-derived cells (BMCs) to repair damaged nervous system; this approach seems particularly attractive in ALS, which is characterized by neuronal degeneration. Aims of the study. To evaluate, at the multicenter setting, feasibility, safety and tolerability, and possible benefit of repeated procedures of G-CSF-induced BMC mobilization in ALS patients.

Patients and methods. Seven Neurology Centers, along with seven Hematology Centers, are participating to the multicenter “STEMALS” trial, that started in June 2006 and will enrol a total of 28 patients, with 4 mobilization procedures for each patients; this is the interim analysis, after 42 mobilization procedures performed on a total of 22 patients. Patient median age is 56 yrs (range 40–64), 14 are male. The protocol includes four cycles of G-CSF, scheduled at 3 mos. intervals. In each cycle, G-CSF is administered at the dose of 5 μg/kg s.c., twice a day, for 4 consecutive days. At each cycle, CBCs and circulating CD34+ cells are determined, since day 0 through day 6.

Results. Overall, 18 patients completed the first G-CSF cycle and all displayed good response; peak values were for WBCs: 41 x103/μL (range 24– 71) at day 3, and for CD34+ve cells: 52/μL (range 8.4–156), at day 4; 16 patients have already completed the second mobilization course, with values of circulating cells matching those of the first cycle (median WBCs/μL: 42x103; median CD34+ve/μL: 60.7); a few patients have undergone the third and fourth cycle, again they consistently displayed high levels of mobilization. Overall, the mobilization procedures were well tolerated, with the exception of a transient increase of growth hormone level in one patient, and a deep venous thrombosis in one patient, both complications did not preclude to conclude the treatment.

Conclusion. The STEMALS trial indicate that: i. the use of G-CSF to induce BMC mobilization is safe, well tolerated and feasible in ALS, even at the multicenter level; ii. so far, few and reversible adverse effects have been recorded; iii. peak values of circulating CD34+ve cells indicate that BMC mobilization capacity in ALS is analogous to that commonly observed in the healthy population; iv. there are no signs of impaired mobilization, after repeated courses of G-CSF administration, performed at few month intervals. A longer follow up is still required to verify possible benefits of the repeated BMC mobilization program in ALS.

Author notes

Disclosure: Research Funding: Some of the Authors have received financial research supports by Roche, Sanofi-Synthelabo and Italfarmaco. Honoraria Information: Some of the authors have been paid as invited speakers at national and international symposia. Off Label Use: G-CSF has been employed to mobilize BMCs in patient with ALS. The drug G-CSF (Myelostim34) used in the protocol has been partially provided by Italfarmaco.