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.

开始日期2021-01-25

申办/合作机构

National Cancer Institute

NCT03515785 / WithdrawnN/A

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.

开始日期2018-12-31

申办/合作机构

Incyte Biosciences International SARL

100 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的临床结果

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100 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的转化医学

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0 项与 BCR-ABL1阳性急性淋巴细胞白血病相关的专利（医药）

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380

项与 BCR-ABL1阳性急性淋巴细胞白血病相关的文献（医药）

2024-09-01·Cancer Diagnosis & Prognosis

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

Article

作者: 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.

2024-07-14·Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi

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

Review

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

酪氨酸激酶抑制剂和免疫靶向药物的应用已经明显改变了BCR::ABL1阳性急性B淋巴细胞白血病的治疗策略和临床结果。2022年，世界卫生组织（WHO）和国际共识分型（ICC）相继对该疾病的分型进行了更新。2023年，美国国立综合癌症网络（NCCN）也首次更新了该疾病的预后分层，其治疗后的微小残留病评估和IKZF1(plus)基因分型是最关键的预后因素。以上更新将对临床诊疗产生重大影响，本文聚焦于该疾病分型和预后评估的最新更新内容展开综述。.

2024-04-04·Blood

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

Article

作者: 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.