CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia

Pacenta, Holly L; Laetsch, Theodore W.; John, Samuel

doi:10.1007/s40272-019-00370-6

Cited by 12 publications

(11 citation statements)

References 64 publications

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“…The relationship between CD19 and ALL has not been fully de ned. Still, it is well known that CD19 is the most densely expressed antigen on B cells' surface in ALL patients and is a highly speci c target for drug development [23] . In particular, CAR T cells can penetrate the BBB into the CNS, killing leukemic cells in the cerebrospinal uid [24] .…”

Section: Discussionmentioning

confidence: 99%

PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia

zhang

Lai

et al. 2022

Preprint

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Objective To identify biomarkers that can predict the recurrence of the central nervous system (CNS) in children with acute lymphoblastic leukemia (ALL). Materials and Methods The transcriptome and clinical data collected by the Children's Oncology Group (COG) collaboration group in the Phase II study and Phase I study of ALL in children were downloaded from the TARGET database. Transcriptome data were analyzed by bioinformatics method to identify core (hub) genes and establish a risk assessment model. Univariate Cox analysis was performed on each clinical data, and multivariate Cox regression analysis was performed on the obtained results and risk score. The children ALL phase I samples collected by the COG collaboration group in the TARGET database were used for verification. Results A total of 1230 differentially expressed genes were screened out between the CNS relapsed and non-relapsed groups. Univariate multivariate Cox analysis of 10 hub genes identified showed that PPARG (HR = 0.78, 95%CI = 0.67–0.91, p = 0.007), CD19 (HR = 1.15, 95%CI = 1.05–1.26, p = 0.003) and GNG12 (HR = 1.25, 95%CI = 1.04–1.51, p = 0.017) had statistical differences. The risk score was statistically significant in univariate (HR = 3.06, 95%CI = 1.30–7.19, p = 0.011) and multivariate (HR = 1.81, 95%CI = 1.16–2.32, p = 0.046) Cox regression analysis. The survival analysis results of the high and low-risk groups were different when the validation group was substituted into the model (p = 0.018). In addition, the CNS involvement grading status at first diagnosis CNS3 vs. CNS1 (HR = 5.74, 95%CI = 2.01–16.4, p = 0.001), T cell vs B cell (HR = 1.63, 95% CI = 1.06–2.49, p = 0.026) were also statistically significant. Conclusions PPARG, GNG12, and CD19 may be predictors of CNS relapse in childhood ALL.

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Section: Discussionmentioning

confidence: 99%

PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia

zhang

Lai

et al. 2022

Preprint

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“…Chimeric antigen receptor (CAR) T cells are genetically engineered to express a receptor that binds to a tumour antigen [ 67 ]. CAR T cells were approved for relapsed or refractory pediatrics and young adults with precursor B-ALL [ 68 , 69 ]. ABL001 (Asciminib) is an investigational treatment that binds to the myristoyl site of the BCR-ABL1 protein [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Preventive Healthcare and Management for Acute Lymphoblastic Leukaemia in Adults: Case Report and Literature Review

et al. 2021

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Acute lymphoblastic leukaemia (ALL) is diagnosed by the presence of at least 20% lymphoblasts in the bone marrow. ALL may be aggressive and include the lymph nodes, liver, spleen, central nervous system (CNS), and other organs. Without early recognition and timely treatment, ALL will progress quickly and may have poor prognosis in clinical scenarios. ALL is a rare type of leukaemia in adults but is the most common type in children. Precipitating factors such as environmental radiation or chemical exposure, viral infection, and genetic factors can be associated with ALL. We report a rare case of ALL with symptomatic hypercalcaemia in an adult woman. The patient presented with general weakness, poor appetite, bilateral lower limbs oedema, consciousness disturbance, and lower back pain for 3 weeks. She had a history of cervical cancer and had undergone total hysterectomy, chemotherapy, and radiation therapy. Her serum calcium level was markedly increased, at 14.1 mg/dl at admission. Neck magnetic resonance imaging, abdominal sonography, abdominal computed tomography, and bone marrow examination were performed. Laboratory data, including intact parathyroid hormone (i-PTH), peripheral blood smear, and 25-(OH) D3, were checked. Bone marrow biopsy showed B cell lymphoblastic leukaemia. Chemotherapy was initiated to be administered but was discontinued due to severe sepsis. Finally, the patient died due to septic shock. This was a rare case of B cell ALL in an adult complicated by hypercalcaemic crisis, which could be a life-threatening emergency in clinical practice. Physicians should pay attention to the associated risk factors. Early recognition and appropriate treatment may improve clinical outcomes.

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“…The relationship between CD19 and ALL has not been fully de ned. Still, it is well known that CD19 is the most densely expressed antigen on B cells' surface in ALL patients and is a highly speci c target for drug development [20] . In particular, CAR T cells can penetrate the BBB into the CNS, killing leukemic cells in the cerebrospinal uid [21] .…”

Section: Discussionmentioning

confidence: 99%

PPARG, GNG12, and CD19 are Potential Independent Predictors of Central Nerve Recurrence in Childhood Acute Lymphoblastic Leukemia

Zhang

et al. 2021

Preprint

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Objective: To identify biomarkers that can predict the recurrence of the central nervous system (CNS) in children with acute lymphoblastic leukemia (ALL), and establish a prediction model. Materials and Methods: The transcriptome and clinical data collected by the Children's Oncology Group (COG) collaboration group in the Phase II study (use for test group) and Phase I study (use for validation group) of ALL in children were downloaded from the TARGET database. Transcriptome data were analyzed by bioinformatics method to identify core (hub) genes and establish a risk assessment model. Univariate Cox analysis was performed on each clinical data, and multivariate Cox regression analysis was performed on the obtained results and risk score. The children ALL phase I samples collected by the COG collaboration group in the TARGET database were used for verification. Results: A total of 1230 differentially expressed genes were screened out between the CNS relapsed and non-relapsed groups. Univariate multivariate Cox analysis of 10 hub genes identified showed that PPARG (HR=0.78, 95%CI=0.67-0.91, p=0.007), CD19 (HR=1.15, 95%CI=1.05-1.26, p=0.003) and GNG12 (HR=1.25, 95%CI=1.04-1.51, p=0.017) had statistical differences. The risk score was statistically significant in univariate (HR=3.06, 95%CI=1.30-7.19, p=0.011) and multivariate (HR=1.81, 95%CI=1.16-2.32, p=0.046) Cox regression analysis. The survival analysis results of the high and low-risk groups were different when the validation group was substituted into the model (p=0.018). In addition, the CNS involvement grading status at first diagnosis CNS3 vs. CNS1 (HR=5.74, 95%CI=2.01-16.4, p=0.001), T cell vs B cell (HR=1.63, 95% CI=1.06-2.49, p=0.026) were also statistically significant. Conclusions: PPARG, GNG12, and CD19 may be predictors of CNS relapse in childhood ALL.

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CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia

Cited by 12 publications

References 64 publications

PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia

PPARG, GNG12, and CD19 are potential independent predictors of central nerve recurrence in childhood acute lymphoblastic leukemia

Preventive Healthcare and Management for Acute Lymphoblastic Leukaemia in Adults: Case Report and Literature Review

PPARG, GNG12, and CD19 are Potential Independent Predictors of Central Nerve Recurrence in Childhood Acute Lymphoblastic Leukemia

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