Effect of low-level BCR-ABL1 kinase domain mutations identified by next-generation sequencing in patients with chronic myeloid leukaemia: a population-based study

Kizilors, Aytug; Crisà, Elena; Lea, Nicholas; Passera, Roberto; Mian, Syed A; Anwar, javaria; Best, Steve; Nicolini, Franck E.; Ireland, Robin; Aldouri, Maadh; Pocock, Christopher; Corbett, Timothy J.; Gale, Richard; Bart-Smith, Emily; Weston-Smith, Simon; Wykes, Clare; Kulasekararaj, Austin; Jackson, Sophie; Harrington, Patrick; McLornan, Donal; Raj, Kavita; Pagliuca, Antonio; Mufti, Ghulam J.; Lavallade, Hugues de

doi:10.1016/s2352-3026(19)30027-4

Cited by 52 publications

(73 citation statements)

References 26 publications

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“…In comparison to other described Illumina‐based NGS protocols (Eyal et al ., ; Kizilors et al ., ), we decided to implement mechanical sheering of one long PCR product in our NGS workflow, to ensure the most homogenous amplicon fragmentation and to reduce fragment loss which may occur while using alternative enzymatic digestion. Despite that enzymatic digestion is slightly more time‐ (1–3 h shorter) and cost‐effective, we showed that it directly affects the sensitivity and reproducibility of mutation detection, especially at low VAF and BCR‐ABL1 transcript levels.…”

Section: Discussionmentioning

confidence: 97%

“…Our Illumina‐based NGS protocol still provided sensitive detection of low‐level mutations (below 3% VAF), but required replicate measurements for their confirmation. More importantly, clinical relevance of such low‐level mutations may vary, as suggested by others (Soverini et al ., ; Kizilors et al ., ). Therefore, in clinical testing, low‐level mutations should mainly be verified in the next or an additional follow‐up sample before making a therapeutic decision.…”

Section: Discussionmentioning

confidence: 98%

“…The NGS platform used most frequently for BCR‐ABL1 KD sequencing is 454 from Roche (Basel, Switzerland) (Machova Polakova et al ., ; Baer et al ., ; Soverini et al ., ; Erbilgin et al ., ). The use of Ion Torrent (Thermo Fisher Scientific, Waltham, MA, USA) technology and the widely implemented Illumina (San Diego, CA, USA) platform has been reported by fewer authors to date (Eyal et al ., ; Deininger et al ., ; Kizilors et al ., ). The majority of NGS protocols for BCR‐ABL1 sequencing on these platforms employ a semi‐nested/nested polymerase chain reaction (PCR), or amplification of multiple overlying amplicons spanning across the whole KD region.…”

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confidence: 98%

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Novel Illumina‐based next generation sequencing approach with one‐round amplification provides early and reliable detection of BCR‐ABL1 kinase domain mutations in chronic myeloid leukemia

et al. 2020

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The occurrence of mutations in the BCR-ABL1 kinase domain (KD) can lead to treatment resistance in chronic myeloid leukaemia patients. Nowadays, next-generation sequencing (NGS) is an alternative method for the detection of kinase domain mutations, compared to routinely used Sanger sequencing, providing a higher sensitivity of mutation detection. However, in the protocols established so far multiple rounds of amplification limit reliable mutation detection to approximately 5% variant allele frequency. Here, we present a simplified, one-round amplification NGS protocol for the Illumina platform, which offers a robust early detection of BCR-ABL1 KD mutations with a reliable detection limit of 3% variant allele frequency.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 98%

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Novel Illumina‐based next generation sequencing approach with one‐round amplification provides early and reliable detection of BCR‐ABL1 kinase domain mutations in chronic myeloid leukemia

et al. 2020

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“…BCR-ABL1 mutations can be detected with sensitivities of about 20% by Sanger sequencing and of about 3% by NGS. The greater sensitivity of NGS enables the early detection of clinically relevant BCR-ABL1 resistance mutations [87,88]. NGS is the recommended technology to detect BCR-ABL1 resistance mutations in patients not responding adequately to TKI.…”

Section: Treatment Options For Resistant Bcr-abl1 Mutationsmentioning

confidence: 99%

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

et al. 2020

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The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available firstline). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

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“…Therefore, the data are not sufficient to make suggestions regarding the choice of the TKI in the second-or subsequent-line setting, apart from the differential sensitivity in patients with the presence of BCR-ABL1 point mutations (Table 6). Because the detection of a mutation is the only factor that can specifically guide the choice of another TKI, 85 when a switch is planned for resistance/failure, a mutational analysis should always be performed using at least Sanger sequencing (SS), and whenever possible using next-generation sequencing (NGS), which is not yet widely available, but being more sensitive than SS [86][87][88][89][90] can avoid a wrong choice in up to 25% of cases. Whether mutational analysis should be performed in the case of nonoptimal response has been debated, but a consensus was not reached.…”

Section: The Choice Of the Tki: After First-linementioning

confidence: 99%

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

et al. 2019

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Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

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Effect of low-level BCR-ABL1 kinase domain mutations identified by next-generation sequencing in patients with chronic myeloid leukaemia: a population-based study

Cited by 52 publications

References 26 publications

Novel Illumina‐based next generation sequencing approach with one‐round amplification provides early and reliable detection of BCR‐ABL1 kinase domain mutations in chronic myeloid leukemia

Novel Illumina‐based next generation sequencing approach with one‐round amplification provides early and reliable detection of BCR‐ABL1 kinase domain mutations in chronic myeloid leukemia

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

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