A Phase III Randomized Trial of Steroids + Tyrosine Kinase Inhibitor (TKI) Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) in Adults

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

Start Date25 Jan 2021

Sponsor / Collaborator

National Cancer Institute

NCT03515785 / WithdrawnNot Applicable

A Postmarketing Observational Cohort Study to Evaluate Effectiveness and Safety of Ponatinib (Iclusig®) in Patients With BCR-ABL Positive ALL in Standard Clinical Practice in Europe - "POSEIDON"

The purpose of this study is to evaluate the effectiveness and safety of ponatinib (Iclusig®) in patients with BCR-ABL positive acute lymphoblastic leukemia (ALL) in standard clinical practice in Europe.

Start Date31 Dec 2018

Sponsor / Collaborator

Incyte Biosciences International SARL

100 Clinical Results associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

100 Translational Medicine associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

0 Patents (Medical) associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

380

Literatures (Medical) associated with BCR-ABL1 positive Acute Lymphoblastic Leukemia

01 Sep 2024·Cancer Diagnosis & Prognosis

Association of PARP1 Expression Levels and Clinical Parameters in Different Leukemic Subtypes With BCR::ABL1 p190+ Translocation

Article

Author: DE Pinho Pessoa, Flávia Melo Cunha ; Ribeiro, Rodrigo Monteiro ; DA Silva, Jean Breno Silveira ; SEABRA, ALINE DAMASCENO ; DE Sousa Oliveira, Deivide ; Dias Nogueira, Beatriz Maria ; DE Moraes Filho, Manoel Odorico ; Burbano, Rommel Rodriguez ; DE MORAIS, GUILHERME PASSOS ; MELLO JÚNIOR, FERNANDO AUGUSTO RODRIGUES ; Moreira-Nunes, Caroline Aquino ; Seabra, Aline Damasceno ; BURBANO, ROMMEL RODRIGUEZ ; DE MORAES FILHO, MANOEL ODORICO ; DE PINHO PESSOA, FLÁVIA MELO CUNHA ; DE Moraes, Maria Elisabete Amaral ; Mello Júnior, Fernando Augusto Rodrigues ; Machado, Caio Bezerra ; DA SILVA, JEAN BRENO SILVEIRA ; MOREIRA-NUNES, CAROLINE AQUINO ; Khayat, André Salim ; DIAS NOGUEIRA, BEATRIZ MARIA ; MACHADO, CAIO BEZERRA ; RIBEIRO, RODRIGO MONTEIRO ; DE Morais, Guilherme Passos ; DE SOUSA OLIVEIRA, DEIVIDE ; KHAYAT, ANDRÉ SALIM ; DE MORAES, MARIA ELISABETE AMARAL

Background/Aim: Although the reciprocal translocation t(9;22)(q34;q11) is a hallmark of chronic myeloid leukemia (CML), it is also present in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Depending on the gene's breakpoint, it is possible to obtain three isoforms, among which p190 stands out for the poor prognosis it induces whenever it appears. Due to the genomic instability induced by BCR::ABL1, it is proposed to expand the applicability of poly-ADP-ribose polymerase-1 (PARP1) and its inhibitors in hematological neoplasms. Materials and Methods: We measured the expression levels of PARP1 by quantitative real-time PCR (qPCR) using TaqMan®, correlating its expression with BCR::ABL1 p190+, to evaluate its influence in the clinic of adult patients. Results: We found that PARP1 is expressed differently in ALL, AML and CML and that p190 transcripts do not follow a linear pattern in these populations. We also found that PARP1 expression is not correlated with age, white blood cell and the amount of p190 transcripts. Conclusion: Despite the lack of statistical correlation between the variables analyzed, the role of PARP1 in BCR::ABL1 leukemia cannot be ruled out, given the instability profile promoted by this translocation. Finally, further studies involving a larger sample of patients are needed, as well as investigations into other molecular pathways that may impact on the pathogenesis of different BCR::ABL1 leukemic subtypes.

14 Jul 2024·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

[The progress in classification and prognosis evaluation of BCR::ABL1 positive acute lymphoblastic leukemia].

Review

Author: Wang, J ; Wang, C ; Mi, J Q ; Yan, Y C

The application of tyrosine kinase inhibitors and targeted immunotherapy has revolutionized the therapeutic strategies and clinical outcome for BCR::ABL1-positive B-cell acute lymphoblastic leukemia (BCR::ABL1(+) B-ALL). The classification was updated successively by the World Health Organization and the International Consensus Classification in 2022. The risk stratification of this entity, for the first time, was modified by the National Comprehensive Cancer Network in 2023, both minimal residual disease assessment and IKZF1(plus) genotyping recognized as critical prognostic factors. These important updates would have significant implications for clinical management. Therefore, this review focused on the latest advances in the classification and prognostic evaluation of BCR::ABL1(+) B-ALL.

04 Apr 2024·Blood

Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL

Article

Author: Schneller, Folker ; Harder, Lana ; Barz, Malwine J. ; Cario, Gunnar ; Baldus, Claudia D. ; Zimmermann, Johannes ; Gökbuget, Nicola ; Stelljes, Matthias ; Bastian, Lorenz ; Denker, Miriam ; Schwartz, Stefan ; Beder, Thomas ; Rohrandt, Christian ; Steffen, Björn ; Hartmann, Alina M. ; Haferlach, Claudia ; Faul, Christoph ; Chitadze, Guranda ; Wittig, Michael ; Brüggemann, Monika ; Bartsch, Lorenz ; Neumann, Martin ; Das Gupta, Dennis ; Pfeifer, Heike ; Iben, Katharina ; Wolgast, Nadine ; Bendig, Sonja ; Walter, Wencke ; Fiedler, Walter ; Brändl, Björn ; Hansen, Björn-Thore ; Müller, Franz-Josef

AbstractDistinct diagnostic entities within BCR::ABL1-positive acute lymphoblastic leukemia (ALL) are currently defined by the International Consensus Classification of myeloid neoplasms and acute leukemias (ICC): “lymphoid only”, with BCR::ABL1 observed exclusively in lymphatic precursors, vs “multilineage”, where BCR::ABL1 is also present in other hematopoietic lineages. Here, we analyzed transcriptomes of 327 BCR::ABL1-positive patients with ALL (age, 2-84 years; median, 46 years) and identified 2 main gene expression clusters reproducible across 4 independent patient cohorts. Fluorescence in situ hybridization analysis of fluorescence-activated cell-sorted hematopoietic compartments showed distinct BCR::ABL1 involvement in myeloid cells for these clusters (n = 18/18 vs n = 3/16 patients; P < .001), indicating that a multilineage or lymphoid BCR::ABL1 subtype can be inferred from gene expression. Further subclusters grouped samples according to cooperating genomic events (multilineage: HBS1L deletion or monosomy 7; lymphoid: IKZF1-/- or CDKN2A/PAX5 deletions/hyperdiploidy). A novel HSB1L transcript was highly specific for BCR::ABL1 multilineage cases independent of HBS1L genomic aberrations. Treatment on current German Multicenter Study Group for Adult ALL (GMALL) protocols resulted in comparable disease-free survival (DFS) for multilineage vs lymphoid cluster patients (3-year DFS: 70% vs 61%; P = .530; n = 91). However, the IKZF1-/- enriched lymphoid subcluster was associated with inferior DFS, whereas hyperdiploid cases showed a superior outcome. Thus, gene expression clusters define underlying developmental trajectories and distinct patterns of cooperating events in BCR::ABL1-positive ALL with prognostic relevance.

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