Immunotherapy in pediatric acute lymphoblastic leukemia

AbstractThe 5-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL) has improved to more than 90% in high-income countries. However, further increases in the intensity of conventional chemotherapy would be associated with significant adverse effects; therefore, novel approaches are necessary. The last decade has seen significant advances in targeted therapy with immunotherapy and molecular therapeutics, as well as advances in risk stratification for therapy based on somatic and germline genetic analysis and monitoring of minimal residual disease. For immunotherapy, the approval of antibody-based therapy (with blinatumomab in 2014 and inotuzumab ozogamicin in 2017) and T cell –based therapy (with tisagenlecleucel in 2017) by the US Food and Drug Administration has significantly improved the response rate and outcomes in patients with relapsed/refractory B-ALL. These strategies have also been tested in the frontline setting, and immunotherapy against a new ALL-associate d antigen has been developed. Incorporating effective immunotherapy into ALL therapy would enable the intensity of conventional chemotherapy to be decreased and thereby reduce associated toxicity, leading to further improvement in survival and quality of life for patients with ALL.
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research

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(NIH/National Cancer Institute) New findings from a clinical trial show that treatment with the immunotherapy drug blinatumomab is superior to standard chemotherapy for children and young adults with high- or intermediate-risk B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed. Those treated with blinatumomab had longer survival, experienced fewer severe side effects, had a higher rate of undetectable residual disease, and were more likely to proceed to a stem cell transplant.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
nski J, Urbano-Ispizua A, Hayden PJ, Kröger N Abstract Chimeric antigen receptor T-cells are a novel class of anti-cancer therapy in which autologous or allogeneic T-cells are engineered to express a chimeric antigen receptor targeting a membrane antigen. In Europe, Tisagenlecleucel (KymriahTM) is approved for the treatment of refractory/relapsed Acute Lymphoblastic Leukaemia in children and young adults as well as relapsed/refractory Diffuse Large B-cell Lymphoma; Axicabtagene ciloleucel (YescartaTM) is approved for the treatment of relapsed/refractory high-grade B-cell Lymphoma and Primary Mediastinal B-cel...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
AbstractPresence of minimal residual disease (MRD) following induction chemotherapy is a well-recognized risk factor to predict relapse in acute lymphoblastic leukemia (ALL). There is paucity of data on MRD and outcome in ALL from India. We share our experience in establishing a flow cytometry-based MRD assay for ALL with emphasis on determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with outcome and other prognostic factors. We prospectively studied MRD in patients with ALL less than 25  years who achieved morphological complete remission with induction therapy. The...
Source: Indian Journal of Hematology and Blood Transfusion - Category: Hematology Source Type: research
Abstract In December 2018 the FDA approved calaspargase pegol-mknl (Asperlas, Servier Pharmaceuticals, Boston MA, USA) for acute lymphoblastic leukemia in children and young adults up to age 21. Asparaginase is a critical component in the treatment of ALL, but the niche for calaspargase within current treatment protocols is unclear. PMID: 31641006 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15 –17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
;o LR Abstract Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0-21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight hepar...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Thromb Haemost Source Type: research
AbstractBackgroundAverage paternal age in the United States has increased substantially in the last few decades. Children of advanced age fathers have a higher incidence of early onset cancer and neuropsychiatric disease.ObjectivesTo quantify the number of population adjusted cases of early ‐onset cancer and neuropsychiatric disease in children attributable to increasing paternal age in the United States.MethodsPaternal age in the United States from 1972 to 2015 was collected using the National Vital Statistics System (NVSS). Population attributable fraction and paternal age ‐specific cumulative incidence rates of seve...
Source: Andrology - Category: Urology & Nephrology Authors: Tags: Original Article Source Type: research
Abstract On December 20, 2018, the Food and Drug Administration approved calaspargase pegol-mknl (CALASP), an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Efficacy was determined based on achievement and maintenance of steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using CALASP, 2500 U/m2 intravenously, every 3 weeks. In a randomized comparison to pegaspargase (PEGASP) every 2 weeks, treatment with CALASP every 3 weeks had a similar safety profile ...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionThe use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Treatment of B-cell acute lymphoblastic leukemia (ALL) and lymphoma using chimeric antigen receptors (CARs) targeting B-cell surface protein CD19 has demonstrated impressive clinical results in children and young adults. Despite the promising results from CD19 CAR therapy, up to 40% of patients, who initially achieve remission, eventually relapse. Relapse or non-response to CD19-directed CAR therapy may be due to low or diminished CD19 expression. Such patients would be predicted to benefit from CAR therapies targeting other B-cell surface proteins, such as CD22.Scientists at the National Cancer Institute ’s (NCI) Pe...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
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