PCR detection of clonal IgH and TCR gene rearrangements at the end of induction as a non‐remission criterion in children with ALL: Comparison with standard morphologic analysis and risk group classification

Scrideli, Carlos Alberto; Queiróz, Rosane Gomes de Paula; Bernardes, José Eduardo; Valera, Elvis Terci; Tone, Luíz Gonzaga

doi:10.1002/mpo.10154

Cited by 17 publications

(12 citation statements)

References 42 publications

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“…Of the 27 patients with leukemic isolates exhibiting molecular clonality, over 50% had more than one clonal locus suitable for MRD quantification, which correlates well with other studies using standard techniques for clonality identification. 13 Although LymphoSIGHT can be used to address oligoclonality and clonal evolution, we elected not to address clonal evolution during the treatment courses of patients in this cohort since for some cases the only sample available for identification of leukemia-associated clonotypes was a relapse sample. Comparison of Ig/TCR-HTS-quantified leukemia burdens in PB and BM revealed the latter to have a median 8.4-fold higher disease burden.…”

Section: Discussionmentioning

confidence: 99%

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Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival

Logan

Vashi

Faham³

et al. 2014

Biology of Blood and Marrow Transplantation

127

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Minimal residual disease (MRD) quantification is an important predictor of outcome after treatment for acute lymphoblastic leukemia (ALL). Bone marrow ALL burden ≥ 10−4 after induction predicts subsequent relapse. Likewise, MRD ≥ 10−4 in bone marrow prior to the initiation of conditioning for allogeneic hematopoietic cell transplantation (allo-HCT) predicts transplant failure. Current methods for MRD quantification in ALL are not sufficiently sensitive for use with peripheral blood specimens and have not been broadly implemented in the management of adults with ALL. Consensus primed immunoglobulin (Ig) and T-cell receptor (TCR) amplification and high-throughput sequencing (HTS) permits use of a standardized algorithm for all patients and can detect leukemia at 10−6 or lower. We applied the Sequenta LymphoSIGHT™ HTS platform to quantification of MRD in 237 samples from 29 adult B-ALL patients before and after allo-HCT. Using primers for the IGH-VDJ, IGH-DJ, IGK, TCRB, TCRD, and TCRG loci, MRD could be quantified in 93% of patients. Leukemia-associated clonotypes at these loci were identified in 52%, 28%, 10%, 35%, 28%, and 41% of patients, respectively. MRD ≥ 10−4 before HCT conditioning predicted post-HCT relapse (HR 7.7, 95% CI 2.0–30, p=0.003). In post-HCT blood samples, MRD ≥ 10−6 had 100% positive predictive value for relapse with median lead-time of 89 days (HR 14; 95% CI 4.7–44, p<0.0001). The use of HTS-based MRD quantification in adults with ALL offers a standardized approach with sufficient sensitivity to quantify leukemia MRD in peripheral blood. Use of this approach may identify a window for clinical intervention prior to overt relapse.

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Section: Discussionmentioning

confidence: 99%

“…Post-therapy MRD burden ≥ 10 −4 in BM aspirates, using either RQ-PCR or MPFC, has been demonstrated to be a more powerful prognostic marker for subsequent relapse than those typically used, including age, WBC count at diagnosis, and cytogenetic alterations. 12, 13 …”

Section: Introductionmentioning

confidence: 99%

Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival

Logan

Vashi

Faham³

et al. 2014

Biology of Blood and Marrow Transplantation

127

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“…Detection of minimal residual disease (MRD) at day 28 of induction therapy was performed by PCR using consensus primers for the detection of a clonal population for TCRγ, IgH and TCRδ. This method can detect one leukemic cell in 10 2 -10 3 normal cells (11,12).…”

Section: Patientsmentioning

confidence: 99%

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Mata

Scrideli

Queiroz

et al. 2006

Braz J Med Biol Res

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Infant acute lymphoblastic leukemia (IALL) is characterized by mixed lineage leukemia (MLL) gene rearrangements, unique gene expression profiles, poor prognosis, and drug resistance. One exception is cytosine arabinoside (Ara-C) to which IALL cells seem to be more sensitive. We quantified mRNA expression of Ara-C key enzymes in leukemic lymphoblasts from 64 Brazilian ALL children, 15 of them presenting MLL gene rearrangement, and correlated it with clinical and biological features. The diagnosis was based on morphological criteria and immunophenotyping using monoclonal antibodies. MLL gene rearrangements were detected by conventional cytogenetic analysis, RT-PCR and/or fluorescence in situ hybridization. The DCK and HENT1 expression levels were determined by real-time quantitative PCR using SYBR Green I. Relative quantification was made by the standard curve method. The results were analyzed by Mann-Whitney and Fisher exact tests. A P value of ≤0.05 was considered to be statistically significant. DCK and HENT1 expression levels were significantly lower in children with MLL gene-rearranged ALL compared to children with MLL germ line ALL (P = 0.0003 and 0.03, respectively). Our results differ from previous ones concerning HENT1 mRNA expression that observed a higher expression level in MLL gene-rearranged leukemias. In conclusion, the expression of the genes related to Ara-C metabolism was lower in MLL-positive children in the sample studied, suggesting the presence of population differences in the expression profile of these genes especially for HENT1.

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“…[8][9][10] The grade of clonality may be of importance in disease progress, with monoclonality considered to be the highest grade.…”

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confidence: 99%

Comparative investigations of T cell receptor γ gene rearrangements in frozen and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis

Christensen

Funder²,

Bendix³

et al. 2006

J Clin Pathol

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PCR detection of clonal IgH and TCR gene rearrangements at the end of induction as a non‐remission criterion in children with ALL: Comparison with standard morphologic analysis and risk group classification

Cited by 17 publications

References 42 publications

Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival

Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival

Cytosine arabinoside-metabolizing enzyme genes are underexpressed in children with MLL gene-rearranged acute lymphoblastic leukemia

Comparative investigations of T cell receptor γ gene rearrangements in frozen and formalin-fixed paraffin wax-embedded tissues by capillary electrophoresis

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