When evaluating all 3 phases, the patients in CP had the fewest ACAs. There were 313 de novo CP patients identified with 294 cases successfully analyzed; 30 patients (10.2%) of patients had ACAs, with the remaining 264 patients only carrying the Ph chromosome abnormality. Of these 30 patients, approximately 50% of them had structural abnormalities and 46.66% had numerical aberrations. These numerical aberrations were mostly hyperdiploid and polypoid cases. The structural ACAs primarily involved translocations other than the ones typically seen in chromosome 9 and 22, including extra copies of Ph and trisomy 8 and 19. Five of the karyotypes identified were considered “rare” with an additional 2 being considered “novel”.

ACAs were seen in 49 patients (16.66%) in the CP with imatinib resistance. With respect to treatment response, ACAs were associated with a worse prognosis.

Comparatively, the AP (40.63%) and BC (50.98%) phases had more ACAs than seen in the CP. The differences between AP and de novo CP (P <.0005)/imatinib resistant CP (P <.009), BC and de novo CP (P <.0001) were all statistically significant.

In contrast, there was no statistical difference between the AP and BC groups (P >.3) and the de novo CP and imatinib-resistant CP groups (P >.1).  Interestingly, there was no difference in lab parameters (including white blood cell and platelet count, hemoglobin, lactate dehydrogenase, and bone marrow blasts) in patients with ACAs compared with those without ACAs except for one subgroup within the BC phase.

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Patients with ACAs in the BC group had statistically significantly higher hemoglobin levels (mean 10) compared with those without ACAs (mean 8.7, P =.017), however, this had no impact on prognosis. Therefore, it does not appear that these lab parameters could be used as a surrogate to identify patients with ACAs as an alternative to the more involved genetic analyses utilized in this study.  

When compared with prior studies that evaluated similar outcomes, the incidence rates of ACAs in this study were fairly similar to prior studies in all 3 CML groups (5%-10% CP, 30%-40% AP, 50%-80% BC).8,9

The median age of study participants (43 years) is relatively young compared with the median age of this patient population seen across previously published studies in other non-Asian countries: the United Kingdom (median age, 65 years), United States (median age, 65 years), Germany (median age, 60 years) and France (median age, 55 years).6,10 Prior studies in Asian countries such as Thailand (median age, 43 years) and South Korea (median age, 37 years) appear consistent with the younger patient ages seen in this study.10 This could be due to environmental exposures in Asian countries or other factors that have not yet been identified.

This study reports several interesting findings. Based on the increasing number of ACAs from CP to AP to BC, there appears to be worsening genetic instability as the disease progresses. As the number of ACAs increases, the prognosis of the patient and treatment response was negatively impacted. Therefore, ACAs could represent interesting drug targets in the future.

There are several potential shortcomings of this study, such as the fact that it included patients from a single center in a single country. Therefore, the results may not be generalizable to all patients.

Based on their results, the authors recommended that the advanced genetic testing used in this study be routinely used in patients with CML. However, not all health care facilities may have access to the type of specialized testing performed in this study (such as GTG-banding, FISH, and SK). And even if there were unrestricted access to these tests, it is unclear if all insurance providers would pay for them. If not, the high costs associated with this specialized testing may have to be covered by the patient upfront, which may preclude the routine use of this type of testing.

Regardless, initial research with ACAs in patients with CML is promising, but future studies will be necessary to further define drug targets that could potentially improve patient outcomes — especially as a patient progresses through the different phases of CML.

References

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