Interestingly, the study found that patients who were already in blast phase at the time of initial diagnoses responded better to treatment than those who had received prior treatment.
“Patients with lymphoid immunophenotype and patients who were not treated with a TKI before transformation to blast phase CML were found to have a longer survival compared with patients with myeloid immunophenotype (P < .001) and those who had received a TKI before transformation to blast phase,” the authors wrote.
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“There’s a couple of possible explanations I can see for this,” Dr Cortes explained. “One is, in the patients who have already gone through therapy, have we selected the worst clone by killing the less aggressive clones with this therapy and whatever survived are the bad apples? Or is it just the fact that it has the ability to transform from start? That tells you that this is a bad disease. So definitely it’s an interesting finding.”
Historically, blast phase CML has been a death sentence. As a 2008 analysis put it: “Blast crisis is the sword of Damocles hanging over every patient with CML. … The current challenge is how well (or how poorly) TKIs improve prognosis after diagnosis of blast crisis, and how we can make best use of the limited options that are available.”2
The challenge, of course, is that CML that has persisted despite initial treatment has already proven its resistance to available therapies.
“In contrast to the chronic phase in which with BCR-ABL a pathogenetically relevant target is available for intervention,” the 2008 paper continued, “no such structure is known for blast crisis.”
Because of this, even TKIs ultimately fail.
“Unfortunately,” the author of a 2010 article wrote, “like all other treatment options, including interferon and allogeneic transplantation, TKIs in advanced-phase disease (accelerated and blast phase) are only modestly effective, producing short remissions, but never cures.”3
The new MD Anderson study, though, did find some hopeful signs of progress.
“The data from the current study suggest that although the outcome is poor, with a median survival of only 12 months, the survival has progressively improved over time,” the authors wrote, highlighting their findings that “there is an improvement in outcome after the introduction of a TKI and after 2005 when second-generation TKIs became increasingly available.”
