Influence of BCR-ABL Transcript Type on Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib

Pagnano, Kátia Bórgia Barbosa; Miranda, Eliana Cristina Martins; Delamain, Márcia Torresan; Duarte, Graciana Alves; Paula, Erich Vinícius De; Lorand-Metze, Irene; Souza, Cármino Antônio de

doi:10.1016/j.clml.2017.06.009

Cited by 31 publications

(77 citation statements)

References 15 publications

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“…Bennour et al found that patients with the e14a2 transcript type were significantly older than patients in the e13a2 group (mean age of 56 years vs 26 years; P = .001). Other studies did not find a correlation between age and transcript types …”

Section: Introductionmentioning

confidence: 79%

“…Many studies found no association between leukocyte counts and hemoglobin levels at the time of diagnosis and the transcript types . However, in their study, the German investigators demonstrated that patients with the e13a2 transcript had significantly higher baseline median leukocyte counts compared with patients with the e14a2 transcript (88 × 10 9 /L vs 65 × 10 9 /L; P <.001), but no such relationship was shown for hemoglobin levels .…”

Section: Introductionmentioning

confidence: 88%

“…Patients were divided into 4 groups according to the frontline TKI therapy received as imatinib at a dose of 400 mg, imatinib at a dose of 800 mg, dasatinib 50 mg twice daily or 100 mg daily, and nilotinib 800 mg/day. Cumulative MMR and MR 4.5 rates were significantly inferior in the e13a2 group compared with the e14a2 and coexpression groups in all treatment arms ( P = .0001 and P = .00001, respectively) (Table ) . With regard to CCyR, patients with the e13a2 transcript who received imatinib at a dose of 400 mg/day had inferior response rates (77%) compared with other TKIs (90%‐95%), but this trend was not observed in patients with the e14a2 or coexpression of the e13a2 plus e14a2 transcripts, in whom the CCyR rate with imatinib at a dose of 400 mg/day was similar (93%) to that of other treatment modalities (93%‐96%) .…”

Section: Introductionmentioning

confidence: 97%

“…The incidence rates of the BCR‐ABL1 transcript types gathered from the full‐text articles are given in Table . Of 26 articles, 22 (85%) showed a higher incidence of the e14a2 transcript whereas only 4 articles demonstrated a higher incidence of the e13a2 transcript.…”

Section: Introductionmentioning

confidence: 99%

“…In the study by Castagnetti et al, patients receiving frontline imatinib were evaluated, and CCyR rates at 12 months for patients with the e13a2 and e14a2 transcripts were 75% and 79%, respectively ( P = .274) (Table ) . The median time to achieve CCyR was 6 months for both groups, but patients having the e13a2 transcript type had significantly inferior MMR rates at 18 months and MR 4 rates at 36 months compared with patients with the e14a2 transcript (52% vs 67% [ P = .001] and 20% vs 30% [ P = .013], respectively).…”

Section: Introductionmentioning

confidence: 99%

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The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

Erçalışkan

Eşkazan

2018

Cancer

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Although the majority of patients with chronic myeloid leukemia do well with treatment with tyrosine kinase inhibitors (TKIs), some patients still have inferior outcomes. There are many factors that might play a part, including the different BCR-ABL1 transcript types at baseline. The current study was performed to determine the possible impact of different transcripts on the treatment responses and outcomes of patients with chronic myeloid leukemia who are receiving TKI therapy. The authors performed a systematic literature search by using the terms "b2a2/b3a2," "e13a2/e14a2," or "transcript type." e14a2 was the more common transcript type. The majority of the studies demonstrated no significant difference regarding age, sex, leukocyte counts, and hemoglobin levels between patients with the e13a2 and e14a2 transcripts. However, in approximately one-half of the studies, the e14a2 transcript was associated with higher platelet counts. Almost no studies demonstrated a significant association between disease risk scores and transcript types. In the majority of studies, having the e14a2 transcript was associated with earlier, deeper, and higher molecular response rates. Although better event-free survival was observed in patients with the e14a2 transcript in some of the studies, the majority demonstrated that transcript type did not have an impact on progression-free and overall survival. Treatment-free remission currently is a topic of much interest, and to the authors' knowledge there are limited data with conflicting results regarding the possible effects of transcript types on the outcomes of patients after discontinuation of TKIs. Because having the e14a2 transcript appears to be related to a favorable outcome, choosing second-generation TKIs for frontline therapy might be a convenient approach in patients with chronic myeloid leukemia with the e13a2 transcript. The authors believe this finding warrants further investigation.

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Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

Erçalışkan

Eşkazan

2018

Cancer

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Response-Related Predictors of Survival and of Treatment-Free Remission in CML

Branford

Shanmuganathan

Hughes

2021

Hematologic Malignancies

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Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools

et al. 2021

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In chronic-phase chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are the standard of care, and treatmentfree remission (TFR) following the achievement of a stable deep molecular response (DMR) has become, alongside survival, a primary goal for virtually all patients. The GIMEMA CML working party recently suggested that the possibility of achieving TFR cannot be denied to any patient, and proposed specific treatment policies according to the patient's age and risk. However, other international recommendations (including 2020 ELN recommendations) are more focused on survival and provide less detailed suggestions on how to choose first and subsequent lines of treatment. Consequently, some grey areas remain. After literature review, a panel of Italian experts discussed the following controversial issues: (1) early prediction of DMR and TFR: female sex, non-high disease risk score, e14a2 transcript and early MR achievement have been associated with stable DMR, but the lack of these criteria is not sufficient to exclude any patient from TFR; (2) criteria for first and subsequent line therapy choice: a number of patient and drug characteristics have been proposed to make a personalized decision; (3) monitoring of residual disease after discontinuation: after the first 6 months, the frequency of molecular tests can be reduced based on MR4.5 persistence and short turnaround time; (4) prognosis of TFR: therapy and DMR duration are important to predict TFR; although immunological control of CML plays a role, no immunological predictive phenotype is currently available. This guidance is intended as a practical tool to support physicians in decision making.

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Influence of BCR-ABL Transcript Type on Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib

Cited by 31 publications

References 15 publications

The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

The impact of BCR‐ABL1 transcript type on tyrosine kinase inhibitor responses and outcomes in patients with chronic myeloid leukemia

Response-Related Predictors of Survival and of Treatment-Free Remission in CML

Making Treatment-Free Remission (TFR) Easier in Chronic Myeloid Leukemia: Fact-Checking and Practical Management Tools

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