What factors predict blood-related side effects of tyrosine kinase inhibitors in chronic myeloid leukemia?

This study aimed to investigate the occurrence of hematological (blood-related) side effects in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.  

This study concluded that bone marrow fibrosis at diagnosis was a predictor of hematological side effects from tyrosine kinase inhibitor treatment in these patients.  

Tyrosine kinase inhibitors (TKIs) are a targeted therapy drugs used for the treatment of chronic myeloid leukemia (CML). A common side effect of TKI use is hematological toxicity (HT).  

It was not known if certain factors at diagnosis could predict HT in patients with CML who receive TKI treatment.  

This study involved 143 newly diagnosed patients with CML who were treated with TKIs. Patients were followed up for an average of 90.8 months. The main outcome evaluated was HT.  

Overall, 68 patients (47.55%) experienced some HT. 18.2% of patients experienced a severe HT. Factors at diagnosis associated with severe HT were marrow fibrosis (MF), age over 60 years and spleen enlargement. Marrow fibrosis is increased reticulin (structural protein like collagen) in the bone marrow. This lowers the function of the bone marrow and causes abnormal cell shape.  

At 1 year, 42.3% of patients with serious HT had a complete cytogenic response (CCyR). The CCyR is when there are no Philadelphia (Ph+) chromosomes present. Ph chromosomes are found on leukemia cells. In patients with low-grade HT, 66.7% of patients had CCyR and in those with no HT, 70.7% had CCyR.

At 18 months, 26.9% of patients with serious HT had a major molecular response (MMR). The MMR is when there are low levels of BCR-ABL genes present. BCR-ABL genes are found in leukemia cells. 42.9% of patients with low-grade HT and 54.7% of patients with no HT had a MMR.

Progression-free survival (PFS) rate at 10 years was higher for patients with low-grade HT (75.9%) and for patients without HT (95.8%) compared to patients with serious HT (56.4%). The 10-year overall survival rate was higher for patients with low-grade HT (87.1%) and without HT (97.4%) compared to patients with serious HT (72.3%). 

This study concluded that serious HT can affect a small number of patients with CML treated with TKIs and it affects prognosis. The authors also concluded that bone marrow fibrosis at diagnosis was a predictor of HT from TKI treatment in these patients. 

Most of the patients included in this study were treated with imatinib. Further studies with other TKIs are needed.