Is the Prognosis of People with Chronic Myeloid Leukaemia Presenting in Accelerated Phase Always Worse Compared with People Presenting in Chronic Phase?
Authors: Yang Sen , Zhang Xiaoshuai , Zhang Mengyu , Gale Robert Peter , Huang Xiao Jun , Jiang Qian 
Published: December 2023

Background Some data, albeit controversial, suggest people with chronic myeloid leukaemia (CML) presenting in accelerated phase have the same prognosis as people with CML presenting in chronic phase but with high-risk co-variates.

Objectives Interrogate the heterogeneity of subjects presenting in accelerated phase and compare their outcomes with persons presenting in high-risk chronic phase.

Methods We interrogated data from 2132 consecutive subjects ≥ 18 years with CML presenting in accelerated (N = 274) or chronic phase (N = 1858). Subjects were seen at Peking University People's Hospital from January, 2006 to June, 2023. Criteria for accelerated phase according to the European LeukemiaNet (ELN) 2020 criteria included: ≥ 1 of the following: (1) blood or bone marrow blasts ≥ 15% but &lt; 30%; (2) blood basophils ≥ 20%; and (3) platelet concentration &lt; 100 × 10E + 9/L unrelated to therapy. Chronic phase was defined according to the ELN 2020 criteria. For subjects in chronic phase ELTS score at diagnosis was calculated and used to classify subjects into risk cohorts. Transformation was defined as blood or bone marrow blasts ≥ 30% during TKI-therapy. Transformation-free survival (TFS) was calculated as the interval from starting TKI-therapy to transformation, death or censored at a transplant or last follow-up. We then compared therapy responses and outcomes between defined accelerated phase cohorts and chronic phase risk cohorts using competing risk models and Kaplan-Meier survival analyses. Cox regression analyses were used to further explore the co-variates associated with therapy responses and outcomes.

Results Amongst the 274 subjects presenting in accelerated phase 205 (75%), 39 (14%) and 31 (11%) were classified based on basophilia, excess blasts or thrombocytopenia. Amongst the 1858 subjects presenting in chronic phase 1220 (66%), 461 (25%) and 176 (9%) were ELTS low-, intermediate- and high-risk. In multi-variable analyses we use chronic phase subjects in ELTS low-, intermediate- and high-risk cohort as reference. Subjects in accelerated phase with basophilia had better therapy responses (MMR, HR = 1.2 [1.0, 1.5], p = 0.05; MR 4, HR = 1.7 [1.3, 2.2], p &lt; 0.001; MR 4.5, HR = 2.0 [1.5, 2.6], p &lt; 0.001) and similar TFS and survival (TFS, HR = 0.9 [0.5, 1.6], p = 0.60; survival, HR = 1.4 [0.6, 3.2], p = 0.45) compared with the ELTS intermediate-risk cohort. Accelerated phase subjects with excess blasts and with thrombocytopenia therapy responses like chronic phase subjects with the ELTS intermediate- and high-risk cohorts. TFS and survival were similar with ELTS high-risk cohort. These comparisons held in subjects receiving initial imatinib-therapy but were less clear in subjects receiving initial 2 nd generation TKI therapy. Similar findings were also obtained using the WHO 2016 criteria.

Conclusions Subjects presenting in accelerated phase defined by basophilia had better therapy responses but similar TFS and survival compared with subjects presenting in chronic phase in the ELTS intermediate-risk cohort. Subjects presenting in accelerated phase with excess blasts or thrombocytopenia had comparable therapy responses compared with subjects presenting in chronic phase in the ELTS intermediate- and high-risk cohorts whereas their TFS and survival were like those or worse compared with subjects presenting in chronic phase in the ELTS high-risk cohort. The implication of our findings is presenting in accelerated phase per se does not always confer a worse prognosis compared with subjects presenting in chronic phase.