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Researchers identify factors associated with survival in patients with blast phase CML

“Previously unknown” prognostic factors – including older age at diagnosis, high bone marrow blast percentage, higher LDH levels and previous tyrosine kinase inhibitor treatments – predicted poorer survival in patients with blast phase chronic myeloid leukemia, according to findings presented at the ASH Annual Meeting and Exposition.

“[Despite] the advent of TKIs, CML-BP remains a challenge to the treating physicians and survival of these patients has not been as great as those in patients with chronic phase [disease],” Preetesh Jain, MBBS, MD, DM, PhD, of the University of Texas MD Anderson Cancer Center, told HemOnc Today.

Preetesh Jain
Preetesh Jain

Jain and colleagues analyzed clinical characteristics, prognostic factors and outcomes of 498 (median age, 52 years) patients who presented to MD Anderson from July 1995 to July 2015 with blast phase CML – identified as 30% or higher blasts or extramedullary disease.

Seventy-two patients presented with blast phase disease at the time of initial diagnosis. Eighty-four presented in an accelerated phase and later progressed, and 112 presented in chronic phase and progressed to blast phase.

Sixty-seven percent of patients presented with myeloid immunophenotype and 29% presented with a lymphoid immunophenotype.

Sixty-one percent of patients had additional chromosomal abnormalities besides the Philadelphia chromosome, including double Philadelphia (17%), trisomy 8 (16%), chromosome 3 aberration (11%), iso17q (7%) and trisomy 19 (4%).

More than three-quarters (84%) of patients had received one or more TKI by the time of transformation.

Median OS was 12 months (10 months, myeloid; 17 months, lymphoid) and median failure-free survival was 5 months.

In a univariate analysis, prognostic factors associated with poorer OS included prior TKI therapy (P = .002) and blast phase arising from patients with accelerated phase (P = .003) disease.In a multivariate analysis, independent prognostic factors for poorer OS included an age of 56 years or older (P < .001), prior TKI (P = .02), LDH levels of 888 or higher (P = .002) and myeloid phenotype (P < .001)

“Our study highlights the fact that CML-BP is still a huge therapeutic challenge and further research is required in this field,” Jain said. “Our data shows that combination therapy with intensive chemotherapy, [along] with hyper-CVAD with second generation TKI followed by stem cell transplantation is the best approach to treat these patients. Clinicians can utilize the prognostic factors that we have identified in this study to anticipate the survival outcome of patients with CML-BP.”

Jain also noted that the researchers are expanding on the results of the study and are conducting molecular studies to potentially identify novel pathways involved in disease transformation to blast phase disease. – by Ryan McDonald

Reference:

Jain P, et al. Abstract 1220. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: Jain reports no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.

“Previously unknown” prognostic factors – including older age at diagnosis, high bone marrow blast percentage, higher LDH levels and previous tyrosine kinase inhibitor treatments – predicted poorer survival in patients with blast phase chronic myeloid leukemia, according to findings presented at the ASH Annual Meeting and Exposition.

“[Despite] the advent of TKIs, CML-BP remains a challenge to the treating physicians and survival of these patients has not been as great as those in patients with chronic phase [disease],” Preetesh Jain, MBBS, MD, DM, PhD, of the University of Texas MD Anderson Cancer Center, told HemOnc Today.

Preetesh Jain
Preetesh Jain

Jain and colleagues analyzed clinical characteristics, prognostic factors and outcomes of 498 (median age, 52 years) patients who presented to MD Anderson from July 1995 to July 2015 with blast phase CML – identified as 30% or higher blasts or extramedullary disease.

Seventy-two patients presented with blast phase disease at the time of initial diagnosis. Eighty-four presented in an accelerated phase and later progressed, and 112 presented in chronic phase and progressed to blast phase.

Sixty-seven percent of patients presented with myeloid immunophenotype and 29% presented with a lymphoid immunophenotype.

Sixty-one percent of patients had additional chromosomal abnormalities besides the Philadelphia chromosome, including double Philadelphia (17%), trisomy 8 (16%), chromosome 3 aberration (11%), iso17q (7%) and trisomy 19 (4%).

More than three-quarters (84%) of patients had received one or more TKI by the time of transformation.

Median OS was 12 months (10 months, myeloid; 17 months, lymphoid) and median failure-free survival was 5 months.

In a univariate analysis, prognostic factors associated with poorer OS included prior TKI therapy (P = .002) and blast phase arising from patients with accelerated phase (P = .003) disease.In a multivariate analysis, independent prognostic factors for poorer OS included an age of 56 years or older (P < .001), prior TKI (P = .02), LDH levels of 888 or higher (P = .002) and myeloid phenotype (P < .001)

“Our study highlights the fact that CML-BP is still a huge therapeutic challenge and further research is required in this field,” Jain said. “Our data shows that combination therapy with intensive chemotherapy, [along] with hyper-CVAD with second generation TKI followed by stem cell transplantation is the best approach to treat these patients. Clinicians can utilize the prognostic factors that we have identified in this study to anticipate the survival outcome of patients with CML-BP.”

Jain also noted that the researchers are expanding on the results of the study and are conducting molecular studies to potentially identify novel pathways involved in disease transformation to blast phase disease. – by Ryan McDonald

Reference:

Jain P, et al. Abstract 1220. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: Jain reports no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.

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