The treatment of patients with chronic myeloid leukemia chronic phase combined with myelofibrosis with tyrosine kinase inhibitors: A Chinese population-based study.
Authors: Zhang Xinlu , Yang Xiudi , Chen Dan , Wang Yi , Feng Weiying , Lu Ying , Qian Honglan , Zhou Mei , Chen Yu , Wu Dijiong , Liu Lirong , Tong Hongyan , Jin Jie , Huang Jian 
Published: June 2024

e18524

Background: Chronic myeloid leukemia (CML) is a type of hematological malignancy characterized by the excessive proliferation of myeloid cells. Studies have shown that the presence of MF in CML patients has been associated with TFR. Identifying and assessing MF in CML patients at the time of diagnosis can provide valuable information for treatment planning and prognostic evaluation. Methods: The study enrolled 1757 CML-CP patients with pathological results of bone marrow biopsy. Patients with incomplete information from laboratory tests and medical records were excluded. The study was approved by the Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine and conducted in accordance with the Declaration of Helsinki. CML was diagnosed according to National Comprehensive Cancer Network (NCCN) 2023 version. Results: Patients with MF were found to be older (p<0.001) and had higher leukocyte (p<0.001) and platelet counts (p<0.001). They were also more likely to experience anemia (p<0.001), splenomegaly (p<0.001), patients with myelofibrosis had a higher percentage of eosinophils (p<0.001) and basophils (p<0.001) and had a higher proportion of peripheral blood blast cells (p<0.001) compared to patients without myelofibrosis. However, there was no significant difference in the male-to-female ratio between the two groups (p=0.690). Patients with MF were more unlikely to achieve certain treatment milestones, including a 3-month early molecular response (3M-EMR) (p<0.001), 6-month BCR-ABLIS ≤ 1% (p<0.001), and 12-month major molecular response (12M-MMR) (p<0.001). The proportion of medium/high-risk patients, as determined by Sokal score (p<0.001), Hasford score (p<0.001), ELTS score (p<0.001), and EUTOS score (p=0.002), was significantly increased in patients with MF (Table 1). Patients with MF had lower OS and PFS compared to patients without MF, indicating a potentially worse prognosis for those with MF. Patients with MF 10-year cumulative incidences of imatinib-therapy failure (p<0.001). However, there was no statistically significant difference in the treatment failure rate with different second-generation TKIs (p=0.222). CML-CP patients with MF who were treated with different TKIs were found that second-generation TKIs were more likely to achieve a 3-month EMR(p=0.009), 6-month BCR-ABLIS ≤ 1% (p=0.019), and 12-month MMR(p=0.015) compared to imatinib. Conclusions: Based on the available data, the results suggest that MF is indeed a poor prognostic factor for patients with CML. This finding highlights the importance of considering MF as a factor in assessing the outlook for CML patients. These findings indicate that second-generation TKIs are more effective in achieving molecular responses compared to imatinib, particularly in the context of myelofibrosis.