Friday, 19 April 2013

Leukaemia risk and mitoxantrone

What risk of dying are you prepared to take with regard to your MS treatment? #MSBlog #MSResearch

Chan A, Lo-Coco F. Mitoxantrone-related acute leukemia in MS: An open or closed book? Neurology. 2013;80(16):1529-33..

Background: Despite the long-standing and extensive use of mitoxantrone (MTZ) for the treatment of aggressive forms of MS, especially in Europe, its benefit-risk profile remains controversial. In particular, the risk of developing therapy-related acute leukemia (TRAL) and cardiotoxicity have led to treatment restrictions for MTZ; however, the precise risk for these severe complications is still unclear. 

Objective: This paper reviews current data on TRAL incidence, research strategies aimed at individual risk stratification, and provide recommendations for hematologic monitoring. 

Methods & Results: A recent meta-analysis indicates a TRAL risk of approximately 0.81%, more than 10-fold higher than in previously reported meta-analyses (0.07%). There also appear to be considerable differences among countries, with recent TRAL risk estimates from Italy as high as 0.93%, compared to the 0.25%-0.41% risk reported from Germany and France. Whereas methodologic differences may partly account for some of these differences, high regional variability may point to exogenous factors such as heterogeneous treatment protocols and cotreatments. In addition, genetic risk factors (MTZ metabolism, DNA repair) might contribute to the individual risk profile. The case of potentially curable MTZ-induced secondary leukemia highlights the need for close hematologic monitoring during and after therapy. 

Conclusions: Intensive collaboration between neurologists and hematologists will likely provide benefits both for research efforts aimed at unraveling TRAL pathogenesis and for clinical practice with improved identification and monitoring of patients at higher risk of MTZ-induced TRAL. This is of particular importance, since treatment alternatives, especially in secondary progressive MS, are sparse.

Mitoxantrone or the "blue devil"

"This meta-analysis indicates that the risk of developing a leukaemia after mitoxantrone treatment is 0.81% or 1 in 123. Mitox causes a specific type of leujaemia that is called PML (promyelocytic myeloid leukaemia) that has a mortality of ~50%. In other words if you are MSer and have a full course of mitoxantrone treatment your risk of dying is ~0.4% or 1 in 250. These risk figures are not to dissimilar to natalizumab-associated PML. What risk are you prepared to take?"

10 comments:

  1. Two different MS-related PMLs, this can be confusing

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    Replies
    1. Quite agree, 2 totally different diseases. The leukaemia one is also called AMLm3 (acute myloid leukaemia type3)

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  2. Well i stopped Tysabri after 2 years due to the risk and felt better I have spent my life risking my life for things i believe in but i did NOT trust the drug dealer ... I mean neurologist they don't even know what causes it and have closed minds to new ideas

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  3. I am on my 2nd year of Mitoxantrone and had a MRI yesterday.
    No active inflammation and the ones existing have reduced to about 60-70%

    prMS, highly active with relapses every 2-3 months which led to a grade of disability of 80 (german method, where 100 is top).

    I also had the option to take Tysabri. But I refuse to use a drug which has a side effect which no one knows how to deal with it.

    Leukaemia is a severe side effect.

    But it depends on the fact how fast you diagnose Leukaemia. In "wild life" Leukaemia is mostly diagnosed by random or if a patient has odd feels. With Mitoxantrone you have monitoring.

    AND it is known how to deal with it. This is not the case with PML (Leukenzephalopathie). If you get diagnosed with PML you have it. Period.

    But everyone has to decide for his own.

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    Replies
    1. correction:
      "No active inflammation and the ones existing have reduced to about 60-70%"

      Have reduced about 60-70% meaning they only have 30-40% left. And some of them have gone

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    2. now that, is a decision tree :)

      glad to see that its working on you

      am on tysabri for 2 ys now free of disease activity. I was not to if previous lesions shrank though....

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  4. Death is preferable to advanced MS.

    Really time that researchers cam up with treatments which stop this disease in its tracks. I could live with stable disability not the thought of climbing up the wretched EDSS ladder. No doubt such treatments are a decade away as they've been for the last 50 years!

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    Replies
    1. they are called the new generation DMT? Alemtzumab? Cladribine etc. did you see the ORACLE results...look to the right to see the powerpoint file

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  5. Mitox was exciting at the start because it used to make my urine turn blue, but then within 48 hours it used to make me sick as a parrot. I did it for a year with five infusions. By the end I thought that I'd rather be dead than have to carry on with it. Horrible medicine.

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