The molecular-cytogenetic characterization and tyrosine kinase inhibitors efficacy in newly diagnosed chronic phase CML patients with variant Philadelphia chromosomes / 中华血液学杂志

ABSTRACT

Objective@#To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh).@*Methods@#The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210.@*Results@#There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) (P=0.269), major molecular response (MMR) (P=0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate (χ2=3.978, P=0.046), especially primary hematological resistance (χ2=7.870, P=0.005), but the difference of CCyR (χ2=0.192, P=0.661), MMR (χ2=0.822, P=0.365), EFS (χ2=0.509, P=0.476), OS (χ2=3.485, P=0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS (RR=0.692, 95%CI 0.393-1.765, P=0.658)、EFS (RR=0.893, 95%CI 0.347-2.132, P=0.126) and PFS (RR=1.176, 95%CI 0.643-2.682, P=0.703).@*Conclusion@#CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn’t affect long-term outcomes and OS.