Is the BCR-ABL/GUSB transcript level at diagnosis an early predictive marker for chronic myeloid leukemia patients treated with imatinib?

Bonecker, Simone; Magnago, Marina; Kaeda, Jaspal; Solza, Cristiana; Renault, Ilana Zalcberg

doi:10.1016/j.bjhh.2014.08.003

Cited by 8 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 7 , 15 – 19 ] However, this classification does not take into account patient-specific factors, such as initial BCR-ABL1 transcript levels, which vary considerably between patients. [ 15 , 24 ] Therefore, the individual decline in the BCR-ABL1 transcript level may be more informative than achieving the 10% landmark per se. Hanfstein and colleagues have studied the relative changes of BCR-ABL1 transcript levels within the initial 3 months of therapy and defined good response as an achievement of a half-log reduction in BCR-ABL1/GUS values.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We and Bonecker have demonstrated that quantification of BCR-ABL1 transcripts at diagnosis by using GUS rather than ABL1 as a reference gene predicts IM response, as this measurement reflects the amount of BCR-ABL1 transcripts within each leukemic cell [25,26]. Therefore, we explored the correlation between BCR-ABL1/GUS IS values at diagnosis and BCR-ABL1/ABL1 IS levels at 3 and 6 months.…”

Section: Resultsmentioning

confidence: 99%

Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

Stella

Zammit²,

Vitale

et al. 2019

IJMS

View full text Add to dashboard Cite

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.

show abstract

“…More accurate results have been reported with GUSB , especially at early time points [ 18 ]. Recent comparative studies of GUSB and ABL1 have shown concordant and correlated results; therefore, both control genes are suggested to be used to predict early molecular response [ 19 , 20 , 21 ]. In general, the ABL1 control gene is used by the majority of laboratories worldwide.…”

Section: Discussionmentioning

confidence: 99%

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

Ceran¹,

Akıncı²,

Uçar³

et al. 2022

Tjh

View full text Add to dashboard Cite

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML. Materials and Methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined. Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others. Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

show abstract

Is the BCR-ABL/GUSB transcript level at diagnosis an early predictive marker for chronic myeloid leukemia patients treated with imatinib?

Cited by 8 publications

References 5 publications

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

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

Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib

Leukemia: Reduction Ratio and Halving Time of BCR: : ABL1 IS Transcript Levels

Contact Info

Product

Resources

About