The BCR‐ABL1 transcript type influences response and outcome in<scp>P</scp>hiladelphia chromosome‐positive chronic myeloid leukemia patients treated frontline with imatinib

Castagnetti, Fausto; Gugliotta, Gabriele; Breccia, Massimo; Sciumè, Mariarita; Levato, Luciano; Albano, Francesco; Vigneri, Paolo; Abruzzese, Elisabetta; Rossi, Giuseppe; Rupoli, Serena; Cavazzini, Francesco; Martino, Bruno; Orlandi, Ester; Pregno, Patrizia; Annunziata, Mario; Usala, Emilio; Tiribelli, Mario; Sica, Simona; Bonifacio, Massimiliano; Fava, Carmen; Gherlinzoni, Filíppo; Bocchia, Monica; Soverini, Simona; Bochicchio, Maria Teresa; Cavo, Michèle; Martinelli, Giovanni; Saglio, Giuseppe; Pane, Fabrizio; Baccarani, Michele; Rosti, Gianantonio

doi:10.1002/ajh.24774

Cited by 83 publications

(131 citation statements)

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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%

“…In addition, in the study by Jain et al, significantly higher platelet levels were observed in the patients coexpressing the transcripts compared with patients with the e13a2 transcript alone. A study from Italy with 559 patients was unable to demonstrate any difference between transcript types ( P = .251) . However, a German study with 1105 patients found that patients with the e13a2 transcript had significantly lower platelet levels compared with those with the e14a2 transcript and those coexpressing transcripts (e13a2 plus e14a2) ( P <.001); however, after dissecting patients according to Euro‐Hasford risk scores, this statistically significant difference disappeared …”

Section: Introductionmentioning

confidence: 92%

“…In nearly all the studies, sex did not appear to have an impact on the transcript types, including the European LeukemiaNet (ELN) cohort, which to our knowledge has the largest sample size . However, a small study consisting of 43 patients from Sudan with CML demonstrated a possible relationship between the e13a2 transcript and male sex, which then was confirmed by other 2 large‐scale studies from Italy (559 patients) and India (200 patients) ( P = .03 and P = .05, respectively). In addition, Lin et al demonstrated that female sex was more frequent among patients coexpressing both the e13a2 and e14a2 transcripts ( P <.05), although no significant difference with regard to sex was shown in the e13a2 or e14a2 transcript groups.…”

Section: Introductionmentioning

confidence: 99%

“…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%

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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: 92%

Section: Introductionmentioning

confidence: 99%

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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Exploration of treatment‐free remission in CML, based on molecular monitoring

Zhang,

Zhou,

Zhou

et al. 2023

Cancer Medicine

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BackgroundTypical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment‐free remission (TFR).MethodsWe conducted a literature review of current developments of treatment‐free remission and molecular monitoring methods.ResultsMore effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies.ConclusionCurrently, predictive indicators for treatment‐free remission outcomes and recurrence are lacking in clinical practice. In future, treatment‐free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment‐free remission.

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The e13a2 BCR‐ABL transcript negatively affects sustained deep molecular response and the achievement of treatment‐free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors

D’Adda

Farina

Schieppati

et al. 2019

Cancer

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Background Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment‐free remission (TFR). Methods The potential predictive role of BCR‐ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors’ center. Results Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR (P = .008) and an sDMR (P = .004) was favored significantly in patients who had the e14a2 transcript. After a median of 68 months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second‐generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second‐generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60 months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance (P = .005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript. Conclusions The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.

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The BCR‐ABL1 transcript type influences response and outcome inPhiladelphia chromosome‐positive chronic myeloid leukemia patients treated frontline with imatinib

Cited by 83 publications

References 45 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

Exploration of treatment‐free remission in CML, based on molecular monitoring

The e13a2 BCR‐ABL transcript negatively affects sustained deep molecular response and the achievement of treatment‐free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors

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