Long-Term Outcomes in Blastic Phase Chronic Myeloid Leukemia - One Center Experience

Introduction: Blastic phase (BP) is rare event at the onset of chronic myeloid leukemia (CML) or during treatment with tyrosine kinase inhibitors (TKI). The objective of this study was to present our experience with BP-CML, focusing on outcome after hematopoietic stem cell transplantation (HSCT).

Methods: Overall, 75 adult patients (male n=45; 60%) with CML in BP were under follow-up in our center. Median age at CML diagnosis and at BP was 40 (14-66) years and 45 (18-66) years, respectively. Initial disease phases were chronic (n=54; 72%), accelerated (n=7; 9%) or blastic (n=14; 19%). Transformation to accelerated phase (AP) preceded BP in 19/54 (35%) patients initially diagnosed in chronic phase (CP) CML. Median time from initial diagnosis and from first line therapy with TKI to BP was 37 (0-186) months and 24 (0-165) months, respectively. Overall survival (OS) was calculated by Kaplan-Meier curves and the log-rank test was used to compare the outcome between different treatment groups.

Results: Most patients (n=46; 61%) underwent allogeneic stem cell transplantation (HSCT). The reasons for not undergoing HSCT in 29/75 (39%) patients were: optimal donor unavailability (n=10), failure of bridge therapy (resistance with active BP in 6 cases or death due to complications 3), other (n=10) (concomitant diseases, patient's choice). More patients were switched to HSCT after TKI+chemotherapy combination (21/31, 68%) versus after mono-TKI or chemotherapy alone (12/24, 50%). Median duration of observation time from BP to death or to the last visit in alive patients reached 16 (0,2-227) months. During this observation period 51 (68%) patients died. Death occurred in 27/46 (59%) HSCT and in 24/29 (83%) non-HSCT groups. Nearly all deaths were related to CML in both groups. The median time from Pto death was 14 (2,3-70) months in HSCT group and 7,6 (0,3-67,5) months in non-SCT patients. The estimated 1- and 2-year OS was 68% and 42%, respectively, for the entire group. OS probability by 1- and 2-year was, respectively, 78% and 56% in HSCT cohort versus 52% and 27% in non-HSCT group (p<0,05). In majority cases (n=26; 56.5%) haplo-identical HSCT was performed. Among them 14/26 (53,8%) deaths occurred with median survival time 14,4 (3-120) months. After matched-related (n=15) or matched-unrelated (n=5) HSCT 12/20 (60%) patients died with median OS time 25,5 (2,3-227) months. Probability of OS by 1- and by 2-year was, respectively, 73% and 48% in haplo-HSCT group versus 84% and 53% in matched-transplant group (p>0,05). Factors that significantly shorten OS after HSCT were BP after previous AP versus disease onset in CP or BP, one line of induction treatment versus 2+ line induction, myeloid/lymphoid versus other type of BP. OS after 2 or subsequent BP was dismal and was comparable to OS in non-HSCT group (p>0,05)

Conclusions: In our observation, the best option of bridge treatment was combination therapy with TKI+chemo. Survival was better with any type of HSCT (haplo-, matched related/unrelated) than without transplantation. Intensified combination therapy with subsequent HSCT immediately after blast reduction appears to be optimal for patients in BP-CML.

Alexeeva:Roche: Other: travel expenses, accommodation, Speakers Bureau. Kulemina:Novartis: Speakers Bureau. Badaev:Abbvie: Speakers Bureau. Shnalieva:Novartis: Consultancy; Biocad: Consultancy. Ivanov:MSD: Research Funding. Shatilova:Abbvie: Honoraria, Speakers Bureau. Girshova:Abbvie: Speakers Bureau. Siordiya:Novartis: Speakers Bureau. Lomaia:Fusion Pharma: Speakers Bureau; Pfizer: Other: Travel, accommodation, and expenses, Speakers Bureau; Novartis: Other: Travel, accommodation, and expenses, Speakers Bureau.