The future of cellular immunotherapy for childhood leukemia

Purpose of review Exciting translational discoveries in recent years have brought realized promise of immunotherapy for children with high-risk leukemias. This review summarizes the current immunotherapeutic landscape with a focus on key clinical trials for patients with acute lymphoblastic leukemia or acute myeloid leukemia. Recent findings Chemotherapy resistance remains a major barrier to cure in children with high-risk leukemias. Immunotherapy approaches have potential to overcome this resistance given alternative mechanisms of action. Based upon preclinical activity and/or success in adult patients, recent clinical trials have demonstrated safety and efficacy of various mAb, antibody–drug conjugate, bispecific T-cell-engaging antibody, natural killer cell, and chimeric antigen receptor-redirected T-cell immunotherapies for children with acute lymphoblastic leukemia or acute myeloid leukemia. Food and Drug Administration approval of several of these immunotherapies has increased the pediatric leukemia therapeutic portfolio and improved clinical outcomes for previously incurable patients. Summary Several antibody-based or cellular immunotherapy modalities have demonstrated appreciable efficacy in children with relapsed or chemotherapy-refractory leukemia via early-phase clinical trials. Some studies have also identified critical biomarkers of treatment response and resistance that merit further investigation. Continued preclinical and clinical evaluation of n...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: HEMATOLOGY AND ONCOLOGY: Edited by Brigitte Widemann Source Type: research

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CONCLUSION: Our findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial. PMID: 32087503 [PubMed - as supplied by publisher]
Source: International Journal of Hygiene and Environmental health - Category: Environmental Health Authors: Tags: Int J Hyg Environ Health Source Type: research
We present the first retrospective analysis mapping its incidence and therapeutic outcomes in patients diagnosed and treated from 2000 to 2017 in the Czech Republic. The cohort comprised 14 patients (10 males, 4 females) with a median age at diagnosis of 39 years (range, 5-68 years). Initially, skin involvement was noted in 10 (71%) patients and bone marrow infiltration was present in 9 (64%). The first complete remission was achieved in 6/14 (43%) patients after acute lymphoblastic leukemia/lymphoma induction therapy and in 3/14 (21%) patients after acute myeloid leukemia regimen. Nine patients underwent allogeneic hemato...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research
CONCLUSION: RBC transfusion in AL patients reflected good adherence to guidelines. However, continuing education in transfusion medicine and prospective chart auditing are needed to improve adherence to established guidelines. PMID: 32056229 [PubMed - as supplied by publisher]
Source: Transfusion - Category: Hematology Authors: Tags: Transfusion Source Type: research
T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing tec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Purpose of review Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with historically poor outcomes. It typically manifests as asymptomatic skin lesions and cytopenias, which result from bone marrow involvement. Less commonly, it will present in lymph nodes or visceral organs as well. Although rare, BPDCN has been discussed more frequently in recent years as new drugs have been developed that could be effective at treating this disease. Recent findings Until recently, treatment for BPDCN commonly included intensive chemotherapy regimens, which are generally reserved f...
Source: Current Opinion in Hematology - Category: Hematology Tags: MYELOID DISEASE: Edited by Martin S. Tallman Source Type: research
For patients with refractory or high-risk hematologic malignancies, like acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a potentially curative approach. Morbidities and mortality associated with current conditioning regimens limit the use of this curative procedure. As a result, many eligible patients do not consider transplant and 2/3 of those transplanted are only able to tolerate a reduced intensity conditioning regimen, which is associated with increased relapse rates (Scott, J Clin Onc 2017).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 128 Source Type: research
The objective of this study was to compare the outcomes of allo-SCT from T cell-repleted haploidentical donors (Haplo) with matched related donors (MRD) and unrelated donors, which include matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10), for patients with acute leukemia.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 449 Source Type: research
Bressan GC Abstract The serine/arginine protein kinases respond to the EGFR-PI3K-AKT signaling module in the context of pre-mRNA alternative splicing regulation. These enzymes (notably SRPK1 and SRPK2) have been found dysregulated in a variety of cancers, which suggests them as promising drug targets in oncology. SRPK2 has been related to leukemia cells proliferation and found preferentially overexpressed in T-cell acute lymphoblastic leukemia (T-ALL). Previously, synergistic combination between vincristine and SRPK inhibitors has been observed in leukemia cells in vitro. Herein we sought to evaluate the in vitro ...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
We present a case of t-ALL occurring 18 months after treatment for metastatic endometrial cancer with a regimen of carboplatin, paclitaxel and radiotherapy. The patient presented with severe pancytopenia and diagnosed with common-B ALL, and the cytogenetic analysis showed a previously unreported deletion in chromosome 19 (q13.1) in 100% of the blast cells. The patient declined further therapy and died 1 month later. This rare but serious side effect of chemo-radiotherapy should be considered when deciding on treatment options for gynaecological cancers. PMID: 31921343 [PubMed]
Source: Ecancermedicalscience - Category: Cancer & Oncology Tags: Ecancermedicalscience Source Type: research
Authors: Patel SH, Vasu S, Guo L, Lemaster O, Byrd JC, Walker A Abstract Acute undifferentiated leukemia (AUL) is a subtype of acute leukemias of ambiguous lineage. There is no standard treatment approach for AUL, although acute lymphoblastic leukemia-like regimens for induction therapy have been used. Additional data suggest that AUL may be better treated as acute myeloid leukemia (AML), given their similarities in genetic, cytogenetic, and gene expression patterns. Somatic mutations of IDH1 are found in 7% to 14% of patients with AML; however, the patient in this study was the first patient with IDH1-mutated AUL ...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
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