Identification of prognostic factors in childhood T‐cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05‐001 and 11‐001

Burns, Melissa; Place, Andrew E.; Stevenson, Kristen E.; Gutiérrez, Alejandro; Forrest, Suzanne J.; Pikman, Yana; Vrooman, Lynda M.; Harris, Marian H.; Weinberg, Olga K.; Hunt, Sarah K.; O’Brien, Judith A.; Asselin, Barbara L.; Athale, Uma H.; Clavell, Luis A.; Cole, Peter D.; Gennarini, Lisa; Kahn, Justine M.; Kelly, Kara M.; Laverdière, Caroline; Leclerc, Jean‐Marie; Michon, Bruno; Schorin, Marshall A.; Sulis, Maria Luisa; Welch, Jennifer Greene; Neuberg, Donna; Sallan, Stephen E.; Silverman, Lewis B.

doi:10.1002/pbc.28719

Cited by 34 publications

(20 citation statements)

References 64 publications

(141 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 42 Therefore, early detection of these variants at diagnosis could further refine risk stratification in HHD which is usually associated with favorable prognosis but still contributes to a significant proportion of relapses in the current treatment era. Regarding T-ALL, those harboring PI3K pathway mutations had an inferior prognosis as previously reported by our group 43 and others. 44,45 Furthermore, RNA-seq identified several dysregulated signaling pathways in T-ALL that may represent novel therapeutic targets for a patient population in whom treatment of primary refractory and recurrent disease remains suboptimal.…”

Section: Discussionsupporting

confidence: 81%

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

et al. 2022

Self Cite

View full text Add to dashboard Cite

The molecular hallmark of childhood ALL is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA-seq is a powerful next-generation sequencing technology with the ability to simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multi-center phase 3 clinical trial for children with newly-diagnosed ALL. Patients enrolled on the DFCI ALL Consortium Protocol 16-001 who consented to optional studies and had available material underwent RNA-seq. RNA-seq was performed in 173 ALL patients. RNA-seq identified at least one alteration in 157 (91%) patients. Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-ALL subgroups: High hyperdiploid (n=36), ETV6-RUNX1/-like (n=31), TCF3-PBX1 (n=7), KMT2A-rearranged (n=5), iAMP21 (n=1), hypodiploid (n=1), BCR-ABL1/-like (n=16), DUX4-rearranged (n=11), PAX5 alterations (n=11), PAX5 P80R (n=1), ZNF384-rearranged (n=4), NUTM1-rearranged (n=1), MEF2D-rearranged (n=1) and Others (n=10). RNA-seq identified 141 nonsynonymous mutations in 93 (54%) patients; the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Ph-like gene signature prediction, results were concordant in 74 (94%) patients. In conclusion, RNA-seq identified several clinically-relevant genetic alterations not detected by conventional methods, supporting the integration of this technology in frontline pediatric ALL trials.

show abstract

Section: Discussionsupporting

confidence: 81%

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some studies did not find significant differences in T-ALL/LBL and ETP-ALL/LBL outcomes, though this may be attributed to incomplete immunophenotyping, small sample size, or suboptimal tissue limiting analysis 11,14,15,19. A recent multicenter study correlated ETP with lower rates of CR and event-free survival, but similar OS; the authors describe ETP as prognostically significant and recommend investigation of novel therapeutics during induction but acknowledge uncertainty beyond induction therapy 20. Postinduction treatment intensification, driven by disproportionately higher MRD in ETP-ALL/LBL, may be confounding outcomes and leading to disparate conclusions.…”

Section: Discussionmentioning

confidence: 99%

A Novel Case of Concurrent T-cell and Early T-cell Precursor Lymphoblastic Lymphoma in an Adolescent Female

Treinen

Abu-Arja

Kahwash

et al. 2021

Journal of Pediatric Hematology/Oncology

View full text Add to dashboard Cite

In the context of an evolving understanding of early T-cell precursor (ETP) lymphoma and leukemia, we present a case of concurrent T-cell lymphoblastic lymphoma and ETP lymphoma in an adolescent female. To our knowledge, this represents the first reported case of both lymphoblastic lymphoma and ETP lymphoma as distinct and conjoined components of the same neoplasm. As an exception to current literature, our patient had a strictly lymphomatous ETP component with no leukemic manifestation. Her ETP component remained viable following induction, supporting ETP resistance to chemotherapy. The patient remains in remission 4 years postallogeneic matched sibling donor bone marrow transplant.

show abstract

“…In ALL, which is characterized by aggressive outgrowth of BM lymphoblasts of either B-cell (B-ALL) or T-cell (T-ALL) origin, MRD is a fundamental prognostic factor, broadly used to define different risks of relapse and to guide clinical decisions, especially for treatment intensification by hematopoietic stem cell transplant (HSCT), both in adult and children setting [ 34 , 35 , 36 , 37 , 38 ]. Originally, seminal studies in pediatric ALL have represented a leading clinical experience of MFC-MRD use in hematologic patients [ 39 , 40 , 41 , 42 , 43 ].…”

Section: Acute Lymphoblastic Leukemia (All)mentioning

confidence: 99%

Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Riva¹,

Nasillo²,

Ottomano³

et al. 2021

Cancers

View full text Add to dashboard Cite

Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCR-based techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies—from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL), to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)—providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings.

show abstract

Identification of prognostic factors in childhood T‐cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05‐001 and 11‐001

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 34 publications

References 64 publications

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001

A Novel Case of Concurrent T-cell and Early T-cell Precursor Lymphoblastic Lymphoma in an Adolescent Female

Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges

Contact Info

Product

Resources

About