Monitoring of minimal residual disease in early T‐cell precursor acute lymphoblastic leukaemia by next‐generation sequencing

Pan, Xiaoqing; Nariai, Naoki; Fukuhara, Noriko; Saitō, Sakae; Katsuoka, Fumiki; Kojima, Kazuyuki; Kuroki, Yoshio; Danjoh, Inaho; Saito, Rumiko; Hasegawa, Shin; Okitsu, Yoko; Kondo, Aiko; Onishi, Yasushi; Nagami, Fuji; Kiyomoto, Hideyasu; Hozawa, Atsushi; Fuse, Nobuo; Nagasaki, Masao; Shimizu, Ritsuko; Yasuda, Jun; Harigae, Hideo; Yamamoto, Masayuki

doi:10.1111/bjh.13948

Cited by 6 publications

(8 citation statements)

References 9 publications

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“…Overall, this study showed that more than 60% of adult ETP-ALL patients are characterized by a least a single mutation in DNMT3A , FLT3 , or NOTCH1 that could guide therapeutic choices in this high-risk subgroup. A more recent WGS analysis study was performed on an adult ETP-ALL case to identify clonal and sub-clonal mutations for subsequent monitoring of MRD [103]. As disease-specific mutations have not yet been identified in ETP-ALL, twelve somatic mutations in known oncogenes were selected and analysed by NGS at distinct time points during the follow-up; this study revealed that WGS analysis for identification of multiple target genes is a precise method for subclonality analysis and for the identification of useful targets in MRD monitoring [103].…”

Section: Next-generation Sequencing (Ngs)mentioning

confidence: 99%

Next-Generation Sequencing in Acute Lymphoblastic Leukemia

Coccaro

Anelli

Zagaria

et al. 2019

IJMS

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Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and accounts for about a quarter of adult acute leukemias, and features different outcomes depending on the age of onset. Improvements in ALL genomic analysis achieved thanks to the implementation of next-generation sequencing (NGS) have led to the recent discovery of several novel molecular entities and to a deeper understanding of the existing ones. The purpose of our review is to report the most recent discoveries obtained by NGS studies for ALL diagnosis, risk stratification, and treatment planning. We also report the first efforts at NGS use for minimal residual disease (MRD) assessment, and early studies on the application of third generation sequencing in cancer research. Lastly, we consider the need for the integration of NGS analyses in clinical practice for genomic patients profiling from the personalized medicine perspective.

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Section: Next-generation Sequencing (Ngs)mentioning

confidence: 99%

Next-Generation Sequencing in Acute Lymphoblastic Leukemia

Coccaro

Anelli

Zagaria

et al. 2019

IJMS

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“…So next generation sequencing and whole genome sequencing to identify the multiple target genes of ETP-ALL is necessary for personalized treatment and MRD monitoring. [29] A new technology of CAR T-cell therapies has a relatively good outcome for B-cell malignancies compared to T-cell. [30] Since so many novel strategies are in research, more large-sample studies are needed to determine the efficacy of new drugs in the treatment of ETP-ALL.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular characterization of early T-cell precursor acute lymphoblastic leukemia

Wang

Wu²,

Zhang³

2018

Medicine

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Rationale:Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a small subtype of T-cell acute lymphoblastic leukemia with a typical immune-phenotype: lack of T-lineage cell surface markers CD1a and CD8 expression, weak or absent CD5 expression, at least one of the myeloid or hematopoietic stem cell markers. It is characterized by high rate of induction failure and the effective unified treatment strategies are still indeterminate. We present 2 ETP-ALL cases.Patient concerns:A 42-year-old man presented with abnormal hemogram for 4 months, intermittent fever for 2 months and cough for 1 week. A 27-year-old woman was admitted to the hospital for a fever and headache for that had persisted for 1 week.Diagnosis:The peripheral blood examination, the bone marrow aspiration and flow cytometry for both patients revealed ETP-ALL.Interventions:Both cases accepted chemotherapy including cytarabine.Outcomes:In case one, the patient reached complete hematological remission with negative minimal residual detected by flow cytometry after the first circle of chemotherapy. In case 2, the patient received complete remission after the second circle of chemotherapy with high doses of cytarabine.Lessons:The application of the high-dose cytarabine in induction chemotherapy of ETP-ALL can bring better outcome. ETP-ALL with myeloid features may benefit from therapies used in myeloid malignancies.

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“…The lack of prognostic significance of MRD negativity by MFC in S2 highlights the need for more sensitive assays to detect MRD. Next‐generation sequencing holds promise in identifying MRD with a higher level of sensitivity than MFC, although experience with this approach is relatively limited . In addition, next‐generation sequencing has the ability to detect subclonal disease that might predispose patients to relapse but that might be missed by MFC, either because of a lack of sensitivity of the flow cytometry assay or because of immunophenotypic shifting of the relapsing clone .…”

Section: Discussionmentioning

confidence: 99%

“…Next-generation sequencing holds promise in identifying MRD with a higher level of sensitivity than MFC, although experience with this approach is relatively limited. 20,21 In addition, next-generation sequencing has the ability to detect subclonal disease that might predispose patients to relapse but that might be missed by MFC, either because of a lack of sensitivity of the flow cytometry assay or because of immunophenotypic shifting of the relapsing clone. 22 In contrast to acute myeloid leukemia, in which clonal heterogeneity and clonal evolution leading to relapse are well established, 23,24 less is known about subclonality in adult ALL.…”

Section: Discussionmentioning

confidence: 99%

Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B‐cell acute lymphoblastic leukemia

Jabbour

Short

Jorgensen

et al. 2016

Cancer

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Background Minimal residual disease (MRD) assessment predicts survival in newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. Methods We identified 78 patients with relapsed/refractory B-ALL who achieved morphologic response with inotuzumab ozogamicin (n=41), blinatumomab (n=11) or mini-hyper-CVD plus inotuzumab (HCVD+ino; n=26) given in either salvage 1 (S1; n=46) or salvage 2 (S2; n=32) and who had MRD assessment by multiparameter flow cytometry at the time of remission. Results MRD negativity was achieved in 41 patients overall (53%). The MRD negativity rate was 57% in S1 and 47% in S2. Among patients in S1, achieving MRD negativity was associated with a longer EFS (median 18 months versus 7 months; 2-year EFS rate 46% versus 17%; P=0.06) and OS (median 27 months versus 9 months; 2-year OS 52% versus 36%; P=0.15). EFS and OS were similar in S2 regardless of MRD response. Among MRD-negative patients who underwent allogeneic stem cell transplant (SCT), EFS and OS were superior for those who underwent SCT in S1 rather than in S2 (P=0.003 and P=0.04, respectively). Patients in S1 who achieved MRD negativity and subsequently underwent SCT had the best outcomes, with a 2-year OS rate of 65%. Conclusions Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can have long-term survival. Patients in S2 generally have poor outcomes regardless of MRD status.

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Monitoring of minimal residual disease in early T‐cell precursor acute lymphoblastic leukaemia by next‐generation sequencing

Cited by 6 publications

References 9 publications

Next-Generation Sequencing in Acute Lymphoblastic Leukemia

Next-Generation Sequencing in Acute Lymphoblastic Leukemia

Clinical and molecular characterization of early T-cell precursor acute lymphoblastic leukemia

Differential impact of minimal residual disease negativity according to the salvage status in patients with relapsed/refractory B‐cell acute lymphoblastic leukemia

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