"Patients With MS Treated With Mitoxandrone (Novatrone) at Higher Risk for Developing Acute Leukemia:

Presented at AAN"


Patients with multiple sclerosis who are treated with a cumulative dose of 82 mg/m[² of Mitoxandrone (MTX) are at a 2.7 higher risk of developing acute leukemia (AL), according to a late-breaking abstract presented on April 30 at the American Academy of Neurology (AAN) 61st Annual Meeting.

The risk seems to increase with higher cumulative doses, and after observing 21 patients develop AL after treatment with MTX, the researchers recommend careful monitoring of any patient already treated with MTX for 6 years after the last treatment.

After preliminary studies suggested a .07% to .25% prevalence of AL in patients with MS treated with MTX, Vittorio Martinelli, University Vita-Salute, Milan, Italy, and colleagues began in 1999 to monitor patients prescribed at least 1 cycle of MTX.

Since then they have gathered data on 2,854 patients with

secondary progressive MS (51%),

relapsing-remitting MS (41%),

primary progressive MS (8%) MS

from 35 treatment centres in Italy.

Results showed the prevalence of AL in patients treated with MTX to be .74% -- much higher than previously thought.

"This rate is significantly higher than what has been previously reported," said Dr. Martinelli. "The potential risk of leukaemia should be carefully considered against the potential benefits of mitoxantrone treatment on every single patient."

The study participants all had at least 1 cycle of MTX treatment and were observed for at least 1 year. A total of 21 people developed leukaemia, 8 of whom died.

Patients who developed leukaemia had more treatment cycles than those who did not (8.6 vs 7.2 cycles). They also had a greater cumulative dose of MTX. Patients receiving a lifetime cumulative dose >=82 mg/m² have a 2.7 higher risk than patients receiving an MTX dose <82 mg/m².

"If increasing the dose to 95 or 110 mg/m², the risk of developing AL is 3.9 higher," Dr. Martinelli said.

On average, AL developed 3 years after the first use of the drug. One patient developed AL 6 years after treatment.

"It is vital that all MS patients treated with Mitoxandrone undergo prolonged and careful hematological follow-up to check for acute leukaemia," concluded Dr. Martinelli.