Understanding Blast Phase Chronic Myeloid Leukemia

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A new study finds some hopeful signs of progress in understanding blast phase CML, which is typically associated with poor outcomes.
A new study finds some hopeful signs of progress in understanding blast phase CML, which is typically associated with poor outcomes.

Despite advances that have extended the lives of patients with chronic myeloid leukemia (CML) to near-normal spans, patients who progress to blast phase face dismal outcomes.

The factors leading to the transformation of the disease to blast phase remain unclear, but an expansive review of CML patient records published in July identified a number of molecular and chromosomal differences that could impact prognosis in blast phase patients.1

“It does appear that the disease may be a little bit more heterogeneous from the beginning than we initially thought, meaning there might be, from the time of diagnosis, some markers of more molecular complexity,” said the study's corresponding author, Jorge Cortes, MD, deputy chair of the department of leukemia, division of cancer medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas. “It appears that these patients already have a disease that clinically looks about the same but it's really not the same disease.”

The study identified aberrations in chromosome 15, chromosome 3, and certain trisomies as indicators of less successful survival outcomes. However, the lack of understanding of their roles and an absence of effective treatment options pose daunting challenges.

“When survival was analyzed according to individual chromosomal aberrations, patients with trisomy 8, trisomy 19, trisomy 17, or Philadelphia chromosome with other cytogenetic abnormalities or those with chromosome 3 or chromosome 15 aberrations were found to have significantly inferior [overall survival] compared with patients without these aberrations,” the authors wrote.

They also noted that patient age and elevated LDH levels “demonstrated a significant correlation with inferior survival outcome,” as did bone marrow blast percentage at the time of transformation, platelet count, and other factors. In addition, men had worse survival outcomes compared with women.

The study involved 477 patients with blast phase CML who were seen at The University of Texas MD Anderson Cancer Center from 1997 to 2016. The findings highlighted the stark contrast between patients with CML in either the chronic or acute phase and those whose disease had advanced to blast phase.

The lifespans of non-blast phase cases receiving proper treatment are measured in decades. And even the previous standard of care calling for lifelong ― and extremely expensive ― daily medication is being called into question. Recent research indicates that some patients with CML who achieve a molecular response (MR4.5) that is sustained for at least a couple of years could stop treatment and still maintain a deep response without therapy.

Those who go into blast phase, however, have an overall survival of less than 12 months, the study's authors stated, with a rate of death of 79%.

“With the widespread use of tyrosine kinase inhibitors (TKIs) for the treatment of patients with CML, the risk of transformation to blast phase has markedly decreased,” the authors wrote. “However, a significant minority of patients will have their disease transform to BP.”

And, the study continued, “this occurs less frequently in patients treated with second-generation TKIs as their initial therapy. … Overall survival has progressively improved from 2000 (ie, the advent of imatinib) to the present date.”

Still, even with the advances in first-line treatment, Dr Cortes said, some 7% to 8% of patients with CML advance to blast phase.

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