Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia

El Missiry, MohamedUniv Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. (author)

In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p< 0.01) and a higher percentage of Ph+ CD34+CD38- cells in the bone marrow (91% vs. 75%, p< 0.05). The major molecular response rates were inferior in the poor responders (at 12m 18% vs. 64%, p< 0.01; 18m 27% vs. 75%, p< 0.01; 24m 55% vs. 87%, p< 0.01). In conclusion, early treatment response analysis defines a biologically distinct patient subgroup with inferior long-term outcomes.

Hjorth-Hansen, HenrikSt Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, St Olavs Hosp, Dept Canc Res & Mol Med, Trondheim, Norway. (author)
Richter, JohanSkane Univ Hosp, Dept Hematol & Vasc Disorders, Lund, Sweden. (author)
Olsson-Strömberg, UllaUppsala universitet,Hematologi(Swepub:uu)ulols170 (author)
Stenke, LeifKarolinska Institutet (author)
Porkka, KimmoUniv Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. (author)
Kreutzman, AnnaUniv Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland. (author)
Mustjoki, SatuUniv Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland.;Univ Helsinki, Dept Clin Chem, Helsinki, Finland. (author)
Univ Helsinki, Hematol Res Unit Helsinki, Dept Hematol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Ctr Comprehens Canc, Helsinki, Finland.St Olavs Hosp, Dept Hematol, Trondheim, Norway.;Norwegian Univ Sci & Technol NTNU, St Olavs Hosp, Dept Canc Res & Mol Med, Trondheim, Norway. (creator_code:org_t)

By the author/editor: El Missiry, Moha ...; Hjorth-Hansen, H ...; Richter, Johan; Olsson-Strömberg ...; Stenke, Leif; Porkka, Kimmo; show more...; Kreutzman, Anna; Mustjoki, Satu; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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