Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia

SummaryChimeric antigen receptor (CAR) T  cells are genetically engineered cells containing fusion proteins combining an extracellular epitope-specific binding domain, a transmembrane and signaling domains of the T cell receptor. The CD19-CAR T cell product tisagenlecleucel has been approved by the US Food and Drug Administration and t he European Medicines Agency for therapy of children and young adults under 25 years with relapsed/refractory B‑cell acute lymphoblastic leukemia (ALL) due to a high overall response rate of 81% at 3 months after therapy. The rates of event-free and overall survival were 50 and 76% at 12 month s. Despite the high initial response rate with CD19-CAR‑T cells in B‑ALL, relapses occur in a significant fraction of patients. Current strategies to improve CAR‑T cell efficacy focus on improved persistence of CAR‑T cells in vivo, use of multispecific CARs to overcome immune escape and new CAR designs. The approved CAR‑T cell products are from autologous T cells generated on a custom-made basis with an inherent risk of production failure. For large scale clinical applications, universal CAR‑T cells serving as “off-the-shelf” agents would be of advantage. During recent years CAR‑T cells have been frequently used for bridging to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed/refractory B‑ALL since we currently are not able to distinguis...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
BPDCN is ultimately a bone marrow disease requiring induction-type eradication therapy followed by hematopoietic stem cell transplant (HSCT) to achieve long-lasting remissions or cure. Various regimens have been applied to this disease with varying success. A cumulative review of the literature suggests more intense regimens have greater efficacy with acute lymphoblastic leukemia regimens preferred to acute myeloid leukemia regimens. This approach benefits fit patients who are eligible for HSCT; however, most BPDCN patients require other treatment options. The recent FDA approval of the CD123-targeted agent tagraxofusp pro...
Source: Hematology/Oncology Clinics of North America - Category: Cancer & Oncology Authors: Source Type: research
This study is planned to investigate the prognostic role of pre-transplant soluble TIM-3 (sTIM-3) levels in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: Pre-transplant serum sTIM-3 levels were measured in 177 allo-HSCT recipients [median age: 36(16-66) years; male/female: 111/66]. Results: Pre-transplant sTIM-3 levels were significantly higher in acute myeloid leukemia (AML) patients compared to acute lymphoblastic leukemia (ALL) patients (p = 0.01). Pre-transplant sTIM-3 levels were significantly lower in patients with abnormal cytogenetics (p = 0.017). Pr...
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
This consensus paper presents the results of an initiative by an expert panel to define a set of indications for the practical use of next ‐generation sequencing forBCR ‐ABL1 kinase domain mutation screening in Philadelphia ‐positive acute lymphoblastic leukemia patients receiving tyrosine kinase inhibitor‐based therapies. Minimal technical and methodological requirements for the analysis and the reporting of results have also been proposed. AbstractEmergence of clones carrying point mutations in theBCR ‐ABL1 kinase domain (KD) is a common mechanism of resistance to tyrosine kinase inhibitor (TKI) ‐based therap...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematological malignancy, derived from plasmacytoid dendritic cells. It mainly occurs in older adults, but has been reported across all age groups. Most patients present with skin lesions with or without marrow involvement and leukemic dissemination. Treatment with high-risk acute lymphoblastic leukemia therapy regimens with central nervous system prophylaxis is recommended in pediatric patients. Stem cell transplant in children is recommended for relapsed/refractory disease or high-risk disease at presentation. New targeted therapies including the ...
Source: Hematology/Oncology Clinics of North America - Category: Cancer & Oncology Authors: Source Type: research
We report a case of donor developing acute lymphoblastic leukemia 8 yrs after donating both bone marrow and peripheral blood hemato...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Case report Source Type: research
AbstractPurpose of ReviewBurkitt ’s lymphoma and its leukemic form (Burkitt cell acute lymphoblastic leukemia) are a highly aggressive disease. We review the classification, clinical presentation, histology, cytogenetics, and the treatment of the disease.Recent FindingsBurkitt ’s lymphoma might be associated with tumor lysis syndrome which is a potentially fatal complication that occurs spontaneously or upon initiation of chemotherapy. Major improvements were made in the treatment of pediatric and adults population using short-course dose-intensive chemotherapy regimens , usually 1 week after a prephase in...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
Conclusion: Therefore, testing for WT1 expression at the time of diagnosis may predict outcomes in adult B-ALL patients who receive only chemotherapy and who do not have the BCR-ABL fusion gene or KMT2A rearrangements. Allo-HSCT may improve the prognosis of patients with low WT1 transcript levels. PMID: 32122281 [PubMed - in process]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
The treatment of adult acute lymphoblastic leukemia in the safety-net hospital setting has been heterogeneous given the lack of standardized guidelines. We retrospectively analyzed the outcomes of 90 ALL patients treated at Harbor-UCLA Medical Center, a public hospital in Los Angeles County which lacks the capacity for therapeutic clinical trials and stem cell transplantation. Referral of patients with high risk features to a transplant center may lead to improved survival.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
In conclusion, the outcomes in ALL patients with the T315I BCR-ABL1 mutation were poor. A better OS can be achieved through ponatinib, CAR-T cells, and bridging to HSCT, but it also has a higher risk of recurrence.
Source: Annals of Hematology - Category: Hematology Source Type: research
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