Background: Relapse remains the primary cause of death after hematopoietic cell transplantation (HCT) for acute leukemia. The ability to identify minimal/measurable residual disease (MRD) the blood could identify patients earlier when immunologic interventions may be more successful. We evaluated a new test that could quantify blood tumor mRNA as leukemia MRD surveillance using droplet digital PCR (ddPCR).
Methods: The multiplex ddPCR assay was developed using tumor cell lines positive for the tumor associated antigens (TAA: WT1, PRAME, BIRC5), with homeostatic ABL1. On IRB-approved protocols, RNA was isolated from mononuclear cells from acute leukemia patients after HCT (n = 31 subjects; n = 91 specimens) and healthy donors (n = 20). ddPCR simultaneously quantitated mRNA expression of WT1, PRAME, BIRC5, and ABL1 and the TAA/ABL1 blood ratio was measured in patients with and without active leukemia after HCT.
Results: Tumor cell lines confirmed quantitation of TAAs. In patients with active acute leukemia after HCT (MRD+ or relapse; n=19), the blood levels of WT1/ABL1, PRAME/ABL1, and BIRC5/ABL1 exceeded healthy donors (p<0.0001, p=0.0286, and p=0.0064 respectively). Active disease status was associated with TAA positivity (1+ TAA vs 0 TAA) with an odds ratio=10.67, (p=0.0070, 95% confidence interval 1.91 - 59.62). The area under the curve is 0.7544. Changes in ddPCR correlated with disease response captured on standard of care tests, accurately denoting positive or negative disease burden in 15/16 (95%). Of patients with MRD+ or relapsed leukemia after HCT, 84% were positive for at least one TAA/ABL1 in the peripheral blood. In summary, we have developed a new method for blood MRD monitoring of leukemia after HCT and present preliminary data that the TAA/ABL1 ratio may may serve as a novel surrogate biomarker for relapse of acute leukemia after HCT.
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http://dx.doi.org/10.3389/fimmu.2022.999298 | DOI Listing |
Am J Clin Oncol
January 2025
Department of Medicine, Punjab Medical College, Faisalabad, Pakistan.
Objectives: The incidence of acute lymphoblastic leukemia (ALL) shows a bimodal distribution, with the first peak in children under 10 years old and the second in adults. It is imperative to understand disparities in ALL-related mortality.
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Indian J Sex Transm Dis AIDS
December 2024
Department of Microbiology and Infectious Diseases, National HIV/AIDS Reference Laboratory, All India Institute of Medical Sciences, New Delhi, India.
National Human Immunodeficiency Virus (HIV) testing programs utilize antibody-based tests for confirming HIV diagnosis which has a diagnostic window period of 23-90 days. In Fiebig acute HIV Stage I-II, an individual has antibody-negative but RNA-positive test results. Here, we present a case of a 54-year-old complete remission acute myeloid leukemia patient, who was recently reported HIV negative by antibody-based tests used in National HIV testing programs.
View Article and Find Full Text PDFBMJ Oncol
July 2024
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Objective: Acute myeloid leukaemia (AML) prognosis is enhanced with intensive remission induction chemotherapy (ICT) in eligible patients. However, ICT eligibility perceptions may differ among healthcare professionals. This nationwide, population-based study aimed to explore regional variation in ICT application and its relation with overall survival (OS).
View Article and Find Full Text PDFExpert Rev Anticancer Ther
January 2025
School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar - Delhi, Punjab, India.
Introduction: Acute Myeloid Leukemia is a heterogeneous hematological malignancy characterized by the uncontrolled proliferation of abnormal myeloid cells. Besides several other genetic abnormalities developed in AML, FLT3 mutations are significant due to their worse prognostic impacts and therapeutic resistance. As a result, these mutations enable AML cells to develop mechanisms for evading immune surveillance.
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