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Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

ABSTRACT: Different factors are used as predictors of unfavorable clinical outcomes in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients. However, new prognostic markers are needed in order to allow treatment to be more accurate, providing better results and an improved quality of life. In the present study, we have characterized the profile of bone marrow soluble mediators as possible biomarkers for risk group stratification and minimal residual disease (MRD) detection during induction therapy. The study featured 47 newly-diagnosed B-cell acute lymphoblastic leukemia (B-ALL) patients that were categorized into subgroups during induction therapy according to risk stratification at day 15 [Low Risk (LR), Low Risk increasing to High Risk (LR→HR) and High Risk (HR)] and the MRD detection on day 35 (MRD^(-) and MRD⁽⁺⁾). Soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1β, IL-6, TNF, IFN-γ, IL-17A, IL-4, IL-5, IL-10 and IL-2) were quantified by cytometric bead array and ELISA. Our findings demonstrated that increased levels of CCL5, IFN-γ and IL-2 at baseline appeared as putative candidates of good prognosis in LR and MRD^(-) subgroups, while CCL2 was identified as a consistent late biomarker associated with poor prognosis, which was observed on D35 in HR and MRD⁽⁺⁾ subgroups. Furthermore, apparently controversial data regarding IL-17A and TNF did not allow the definition of these molecules as either positive or negative biomarkers. These results contribute to the search for novel prognostic indicators, and indicate the potential of bone marrow soluble mediators in prognosis and follow-up of B-ALL patients during induction therapy.

SUBMITTER: Kerr MWA

PROVIDER: S-EPMC8503185 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

Kerr Marlon Wendell Athaydes MWA Magalhães-Gama Fábio F Ibiapina Hiochelson Najibe Santos HNS Hanna Fabíola Silva Alves FSA Xabregas Lilyane Amorim LA Alves Eliana Brasil EB Pimentel João Paulo Diniz JPD Carvalho Maria Perpétuo Socorro Sampaio MPSS Tarragô Andréa Monteiro AM Teixeira-Carvalho Andréa A Martins-Filho Olindo Assis OA da Costa Allyson Guimarães AG Malheiro Adriana A

Frontiers in oncology 20210927

Different factors are used as predictors of unfavorable clinical outcomes in B-Cell Acute Lymphoblastic Leukemia (B-ALL) patients. However, new prognostic markers are needed in order to allow treatment to be more accurate, providing better results and an improved quality of life. In the present study, we have characterized the profile of bone marrow soluble mediators as possible biomarkers for risk group stratification and minimal residual disease (MRD) detection during induction therapy. The st ...[more]

PMID: 34646761

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Project description:BackgroundChildren with B-cell acute lymphoblastic leukemia (B-ALL) have an immune imbalance that is marked by remodeling of the hematopoietic compartment, with effects on peripheral blood (PB). Although the bone marrow (BM) is the main maintenance site of malignancy, the frequency with which immune cells and molecules can be monitored is limited, thus the identification of biomarkers in PB becomes an alternative for monitoring the evolution of the disease.MethodsHere, we characterize the systemic immunological profile in children undergoing treatment for B-ALL, and evaluate the performance of cell populations, chemokines and cytokines as potential biomarkers during clinical follow-up. For this purpose, PB samples from 20 patients with B-ALL were collected on diagnosis (D0) and during induction therapy (days 8, 15 and 35). In addition, samples from 28 children were used as a control group (CG). The cellular profile (NK and NKT-cells, Treg, CD3+ T, CD4+ T and CD8+ T cells) and soluble immunological mediators (CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-6, TNF, IFN-γ, IL-17A, IL- 4, IL-10 and IL-2) were evaluated via flow cytometry immunophenotyping and cytometric bead array assay.ResultsOn D0, B-ALL patients showed reduction in the frequency of cell populations, except for CD4+ T and CD8+ T cells, which together with CCL2, CXCL9, CXCL10, IL-6 and IL-10 were elevated in relation to the patients of the CG. On D8 and D15, the patients presented a transition in the immunological profile. While, on D35, they already presented an opposite profile to D0, with an increase in NKT, CD3+ T, CD4+ T and Treg cells, along with CCL5, and a decrease in the levels of CXCL9, CXCL10 and IL-10, thus demonstrating that B-ALL patients present a complex and dynamic immune network during induction therapy. Furthermore, we identified that many immunological mediators could be used to classify the therapeutic response based on currently used parameters.ConclusionFinally, it is noted that the systemic immunological profile after remission induction still differs significantly when compared to the GC and that multiple immunological mediators performed well as serum biomarkers.

Project description:BackgroundFailure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL).MethodsWe identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients.ResultsPatients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only.ConclusionsPediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche Krebshilfe and others.).

Project description:BackgroundInfection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection.MethodsThis was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study. A propensity score-weighted logistic regression model was used to adjust for confounders.ResultsOf 344 included patients, 173 received no prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other prophylaxis regimens. Patients receiving prophylaxis had longer duration of neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely bacterial infection, and bloodstream infection by ≥70%. Levofloxacin prophylaxis alone reduced these infections, but it also reduced cephalosporin, aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile infection by >95%. No increase in breakthrough infections with antibiotic-resistant organisms was seen, but this cannot be excluded.ConclusionsThis is the largest study to date of antibacterial prophylaxis during induction therapy for pediatric ALL and the first to include a broad-spectrum fluoroquinolone. Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin prophylaxis also minimized the use of treatment antibiotics and drastically reduced C. difficile infection. Although long-term antibiotic-resistance monitoring is needed, these data support using targeted prophylaxis with levofloxacin in children undergoing induction chemotherapy for ALL.Clinical trials registrationNCT00549848.

Dataset Information

Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

Publications

Bone Marrow Soluble Immunological Mediators as Clinical Prognosis Biomarkers in B-Cell Acute Lymphoblastic Leukemia Patients Undergoing Induction Therapy.

Similar Datasets

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