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29d
Distinct clinical characteristics of DUX4 and PAX5 altered childhood B-lymphoblastic leukemia. (PubMed, Blood Adv)
In MS2010, with vincristine at day 1, no day 8 poor PB response was observed in DUX4 subtype (P=0.03)...Compared to MS2003, outcome of PAX5alt B-ALL with IKZF1 co-deletion was improved by treatment intensification in MS2010 (5-year CIR 80.0% vs 0%; P=0.05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 co-deletion.
Clinical • Journal
|
ETV6 (ETS Variant Transcription Factor 6) • RUNX1 (RUNX Family Transcription Factor 1) • IKZF1 (IKAROS Family Zinc Finger 1) • PAX5 (Paired Box 5)
|
vincristine
2ms
Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov)
P2, N=94, Completed, St. Jude Children's Research Hospital | Active, not recruiting --> Completed
Clinical • Trial completion
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • cytarabine • etoposide IV • vincristine • methotrexate • clofarabine • mitoxantrone • Oncaspar liquid (pegaspargase) • Vumon (teniposide) • mercaptopurine • Proleukin (aldesleukin) • Decadron (dexamethasone) • cyclophosphamide intravenous • hydrocortisone • vinblastine
4ms
Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia. (PubMed, Clin Cancer Res)
Our study represents a powerful conceptual framework for combinatorial drug discovery based on systematic interrogation of synergistic vulnerability pathways with pharmacologic inhibitor validation in preclinical human leukemia models.
Journal • Combination therapy
|
ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • STAT5B (Signal Transducer And Activator Of Transcription 5B)
|
Venclexta (venetoclax) • dasatinib • Jakafi oral (ruxolitinib)
5ms
Epigenetic biomarkers of prenatal tobacco smoke exposure are associated with gene deletions in childhood acute lymphoblastic leukemia. (PubMed, Cancer Epidemiol Biomarkers Prev)
Analyses of deletion breakpoint sequences are required to further understand the mutagenic effects of tobacco smoke in childhood ALL.
Clinical • Journal
|
HRD (Homologous Recombination Deficiency) • CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1)
6ms
Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov)
P2, N=94, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Apr 2021 --> Jul 2021 | Trial primary completion date: Apr 2021 --> Jul 2021
Clinical • Trial completion date • Trial primary completion date
|
CD20 (Membrane Spanning 4-Domains A1)
|
CD20 expression
|
Rituxan (rituximab) • cytarabine • etoposide IV • vincristine • methotrexate • clofarabine • mitoxantrone • Oncaspar liquid (pegaspargase) • Vumon (teniposide) • mercaptopurine • Proleukin (aldesleukin) • Decadron (dexamethasone) • cyclophosphamide intravenous • hydrocortisone • vinblastine
7ms
How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC (PubMed, Bull Cancer)
In Europe, tisagenlecleucel (Kymriah™) has a marketing authorization for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and young adults and for the relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta™) is the treatment of relapsed/refractory DLBCL and mediastinal B-cell lymphoma. Both products are "living drugs" and genetically modified autologous T cells directed against CD19 which is an antigen expressed throughout B lymphoid differentiation and on many B malignancies. This collaborative work - part of a series of expert works on the topic - aims to provide practical advice to assist collection facilities that procure the starting material i.e. blood mononuclear cells for autologous CAR T-cell manufacturing.
Review • Journal • CAR T-Cell Therapy
|
CD19 (CD19 Molecule)
|
Kymriah (tisagenlecleucel-T) • Yescarta (axicabtagene ciloleucel)
7ms
Research Advances in the Treatment of B-Cell Acute Lymphoblastic Leukemia Based on Surface Antigen Expression --Review (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.
Review • Journal • IO biomarker
|
CD20 (Membrane Spanning 4-Domains A1) • CD22 (CD22 Molecule)
7ms
Impact of CD105 Flow-Cytometric Expression on Childhood B-Acute Lymphoblastic Leukemia. (PubMed, J Blood Med)
Values higher than 2.5 Specific fluorescence indices (SFIs) and 35% expression were sensitive predictors to induction failure. CD105 can be considered as a potential prognostic marker for the detection of response to induction therapy in childhood B-ALL, and it can serve to optimize treatment decisions.
Clinical • Journal
|
ENG (Endoglin)
8ms
Successful Treatment of TCF3-HLF-positive Childhood B-ALL with Chimeric Antigen Receptor T-Cell Therapy. (PubMed, Clin Lymphoma Myeloma Leuk)
CAR-T cells can effectively treat relapsed/refractory TCF3-HLF-positive childhood B-ALL with acceptable toxicity, which could be a new treatment option for this subtype compared with chemotherapy or HSCT.
Clinical • Journal • CAR T-Cell Therapy
|
CD19 (CD19 Molecule) • TCF3 (Transcription Factor 3) • CD22 (CD22 Molecule)
|
fludarabine IV
9ms
Copy Number Alterations are Associated With Associated With the Risk of Very Early Relapse in Pediatric B-lineage Acute Lymphoblastic Leukemia: A Nested Case-control MIGICCL Study. (PubMed, Arch Med Res)
Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.
Clinical • Journal
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A)
|
CDKN2A deletion
9ms
Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC (PubMed, Bull Cancer)
In Europe, tisagenlecleucel (Kymriah) has a marketing authorization for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia in children and young adults and of R/R diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta) is the treatment of DLBCL and primary R/R mediastinal B-cell lymphoma. The two products are autologous T-cells directed against CD19. This collaborative work, part of a series of expert opinion-based work, aims to give practical advice to help centers in selection of patients for commercially available CAR T-cell treatment.
Clinical • Review • Journal • CAR T-Cell Therapy
|
CD19 (CD19 Molecule)
|
Kymriah (tisagenlecleucel-T) • Yescarta (axicabtagene ciloleucel)
10ms
MLPA and DNA index improve the molecular diagnosis of childhood B-cell acute lymphoblastic leukemia. (PubMed, Sci Rep)
Other genetic alterations including iAMP21, IKZF1 deletions, ERG deletions, PAX5, which have clinical significance or are associated with novel subtypes of ALL, were identified. In conclusion, appropriate application of MLPA aids the identifications of CNV and aneuploidy in childhood B-ALL.
Clinical • Journal
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ETV6 (ETS Variant Transcription Factor 6) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5) • EBF1 (EBF Transcription Factor 1)
|
IKZF1 deletion
11ms
Down-Regulated FOXO1 in Refractory/Relapse Childhood B-Cell Acute Lymphoblastic Leukemia. (PubMed, Front Oncol)
Lower FOXO1 expression was associated with prednisone and cyclophosphamide resistance. Low FOXO1 transcription was associated with high-risk stratification and relapse in children with B-ALL, probably due to multi-drug resistance.
Clinical • Journal
|
FOXO1 (Forkhead box O1) • MEIS1 (Meis Homeobox 1)
|
prednisone • cyclophosphamide intravenous
11ms
[VIRTUAL] CHANGE OF LINEAGE IN LEUKEMIA WITH KMT2A REARRANGEMENT - CASE REPORT (HEMO 2020)
Currently, a patient undergoing rescue treatment with Cytarabine and Cladribine, scheduled for allogeneic bone marrow transplantation. Acute Leukemias with alterations in the MLL gene form a separate group in relation to clinical aggressiveness and prognosis. The significance of the translocations that involve this gene in leukemia with lineage change is not fully recognized. It is believed that there may be subclone selection or even epigenetic changes induced by chemotherapy.
Clinical
|
KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD19 (CD19 Molecule) • CD36 (thrombospondin receptor) • CD14 • CD33 (CD33 Molecule) • CD7 (CD7 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • FUT4 (Fucosyltransferase 4)
|
MLL rearrangement • CD19 expression
|
cytarabine • cladribine
12ms
[VIRTUAL] Therapeutic Targets in Childhood B-Acute Lymphoblastic Leukemia : What about HER2/Neu? (ASH 2020)
For example, trastuzumab could be a potential immunotherapy in the HER2/neu expressing group, especially regarding their poorer prognosis. Moreover, CD38 and HER2/neu are good candidates for monitoring MRD. These results are of interest as it has been shown that monitoring MRD early was prognostic on patients’ outcome.
Clinical • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • CD20 (Membrane Spanning 4-Domains A1) • CD38 (CD38 Molecule)
|
HER-2 expression
|
Herceptin (trastuzumab)
1year
Evolution of the epigenetic landscape in childhood B acute lymphoblastic leukemia and its role in drug resistance. (PubMed, Cancer Res)
Three novel, relapse-specific super-enhancers were shared by a majority of patients including one associated with S100A8, the top upregulated gene seen at relapse in childhood B-ALL. Overall, our results support a role of the epigenome in clonal evolution and uncover new candidate pathways associated with relapse.
Clinical • Journal
|
S100A8 (S100 Calcium Binding Protein A8)
1year
Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B-lymphoblastic leukaemia: Ma-Spore ALL 2010 Study. (PubMed, Br J Clin Pharmacol)
We showed that in childhood B-ALL, the intracellular VCR levels in lymphoblasts affected treatment outcomes. The intracellular VCR level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.
Clinical • Journal
|
ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
ABCB1 G1236T + ABCB1 G2677T • ABCB1 G2677T
|
vincristine
1year
Therapeutic targets in childhood B-acute lymphoblastic leukemia: what about HER2/neu? (PubMed, Hematol Oncol)
Trastuzumab could also be a potential interesting immunotherapy in the HER2/neu expressing group, especially in relapsed childhood ALL. In conclusion, these 4 antigens could be alternatives of interest especially since CD19 can be downmodulated after current therapies targeting this antigen. Trastuzumab could also be a potential interesting immunotherapy in the HER2/neu expressing group, especially in relapsed childhood ALL.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • CD20 (Membrane Spanning 4-Domains A1) • CD19 (CD19 Molecule) • CD38 (CD38 Molecule)
|
HER-2 expression
|
Herceptin (trastuzumab)
1year
[VIRTUAL] High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements in B-lineage acute lymphoblastic leukemia (ESHG 2020)
The innovative study provides pathbreaking analyses of TRA occurrence in B-ALL at the DNA level and suggests that particular TRA rearrangements may be of clinical relevance in childhood B-ALL by adding a significant marker to MRD detection panel based on TCR/BCR rearrangements analysis. The study is supported by PFBR grants 20-015-00462, 18-29-09132.
IO biomarker
|
CD33 (CD33 Molecule)
over1year
Clinical • Enrollment closed
|
MLL rearrangement
|
cytarabine • doxorubicin hydrochloride • vincristine • methotrexate • leucovorin calcium • mercaptopurine delayed release (DR6MP) • Oncaspar liquid (pegaspargase) • Decadron (dexamethasone) • cyclophosphamide intravenous • dexamethasone injection