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Blood Cancer Journal Jun 2017Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The... (Review)
Review
Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults, with an incidence of over 6500 cases per year in the United States alone. The hallmark of ALL is chromosomal abnormalities and genetic alterations involved in differentiation and proliferation of lymphoid precursor cells. In adults, 75% of cases develop from precursors of the B-cell lineage, with the remainder of cases consisting of malignant T-cell precursors. Traditionally, risk stratification has been based on clinical factors such age, white blood cell count and response to chemotherapy; however, the identification of recurrent genetic alterations has helped refine individual prognosis and guide management. Despite advances in management, the backbone of therapy remains multi-agent chemotherapy with vincristine, corticosteroids and an anthracycline with allogeneic stem cell transplantation for eligible candidates. Elderly patients are often unable to tolerate such regimens and carry a particularly poor prognosis. Here, we review the major recent advances in the treatment of ALL.
Topics: Female; History, 21st Century; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 28665419
DOI: 10.1038/bcj.2017.53 -
Computational and Mathematical Methods... 2018Leukaemia is a form of blood cancer which affects the white blood cells and damages the bone marrow. Usually complete blood count (CBC) and bone marrow aspiration are... (Review)
Review
Leukaemia is a form of blood cancer which affects the white blood cells and damages the bone marrow. Usually complete blood count (CBC) and bone marrow aspiration are used to diagnose the acute lymphoblastic leukaemia. It can be a fatal disease if not diagnosed at the earlier stage. In practice, manual microscopic evaluation of stained sample slide is used for diagnosis of leukaemia. But manual diagnostic methods are time-consuming, less accurate, and prone to errors due to various human factors like stress, fatigue, and so forth. Therefore, different automated systems have been proposed to wrestle the glitches in the manual diagnostic methods. In recent past, some computer-aided leukaemia diagnosis methods are presented. These automated systems are fast, reliable, and accurate as compared to manual diagnosis methods. This paper presents review of computer-aided diagnosis systems regarding their methodologies that include enhancement, segmentation, feature extraction, classification, and accuracy.
Topics: Algorithms; Bayes Theorem; Cluster Analysis; Computational Biology; Diagnosis, Computer-Assisted; Fractals; Fuzzy Logic; Humans; Image Interpretation, Computer-Assisted; Lymphocytes; Models, Statistical; Neural Networks, Computer; Pattern Recognition, Automated; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Support Vector Machine
PubMed: 29681996
DOI: 10.1155/2018/6125289 -
American Journal of Human Genetics Oct 2021Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite overlap between genetic risk loci for ALL and hematologic traits, the etiological...
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Despite overlap between genetic risk loci for ALL and hematologic traits, the etiological relevance of dysregulated blood-cell homeostasis remains unclear. We investigated this question in a genome-wide association study (GWAS) of childhood ALL (2,666 affected individuals, 60,272 control individuals) and a multi-trait GWAS of nine blood-cell indices in the UK Biobank. We identified 3,000 blood-cell-trait-associated (p < 5.0 × 10) variants, explaining 4.0% to 23.9% of trait variation and including 115 loci associated with blood-cell ratios (LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio). ALL susceptibility was genetically correlated with lymphocyte counts (r = 0.088, p = 4.0 × 10) and PLR (r = -0.072, p = 0.0017). In Mendelian randomization analyses, genetically predicted increase in lymphocyte counts was associated with increased ALL risk (odds ratio [OR] = 1.16, p = 0.031) and strengthened after accounting for other cell types (OR = 1.43, p = 8.8 × 10). We observed positive associations with increasing LMR (OR = 1.22, p = 0.0017) and inverse effects for NLR (OR = 0.67, p = 3.1 × 10) and PLR (OR = 0.80, p = 0.002). Our study shows that a genetically induced shift toward higher lymphocyte counts, overall and in relation to monocytes, neutrophils, and platelets, confers an increased susceptibility to childhood ALL.
Topics: Adult; Aged; Biomarkers, Tumor; Blood Platelets; Case-Control Studies; Child; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lymphocytes; Male; Mendelian Randomization Analysis; Middle Aged; Monocytes; Neutrophils; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Prospective Studies; Quantitative Trait Loci; United Kingdom
PubMed: 34469753
DOI: 10.1016/j.ajhg.2021.08.004 -
Blood Advances Jul 2023Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify...
Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 "classical" ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis. IGH-CRLF2 and IGH-EPOR were found by abnormally high levels of expression of CRLF2 or EPOR. DUX4-rearranged was identified by the unusual expression of DUX4 genes and an alternative exon of ERG, or by clustering analysis of gene expression. PAX5-driven ALL, including fusions, intragenic amplifications, and mutations were identified by single-nucleotide variant analysis and manual inspection using the IGV software. Exon junction analysis allowed detection of some intragenic ERG and IKZF1 deletions. CRLF2-high associated with initial white blood cell (WBC) counts of ≥50 × 103/μL and GATA3 risk alleles (rs3781093 and rs3824662), whereas ABL/JAK2/EPOR-fusions associated with high WBC counts, National Cancer Institute's high-risk classification, and IKZF1del. ZNF384-fusions associated with CALLA-negativity and NUTM1-fusions in infants. In conclusion, targeted RNA sequencing further classified 66.7% (96 of 144) B-other ALL cases. All BCP-ALL subgroups, except for iAMP21, hyperdiploid and hypodiploid cases, were identified. Curiously, we observed higher frequencies of females within B-rest ALLs and males in PAX5-driven cases.
Topics: Male; Infant; Female; Humans; Child; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Mutation; Chromosome Aberrations; Base Sequence; Sequence Analysis, RNA
PubMed: 36848637
DOI: 10.1182/bloodadvances.2022009179 -
Medicine Apr 2021Several studies have reported an association between the rapidity of reduction in peripheral blood blast count or recovery of normal hematopoiesis and treatment outcome...
Several studies have reported an association between the rapidity of reduction in peripheral blood blast count or recovery of normal hematopoiesis and treatment outcome during therapy in children with acute lymphoblastic leukemia (ALL). However, little is known about the impact of both of these aspects on prognosis in pediatric ALL. Accordingly, the purpose of this study was to evaluate whether the combined use of blood blast count and platelet count could predict event-free survival (EFS) and overall survival (OS) when minimal residual disease (MRD) detection was not available.A total of 419 patients aged 0 to 14 years diagnosed and treated for ALL between 2011 and 2015 were enrolled.Patients with a blast count ≥0.1 × 109/L on day 8 exhibited significantly lower survival rates than that in those with blast counts <0.1 × 109/L. The EFS and OS in patients with platelet count ≥100 × 109/L on day 33 were significantly higher than those with platelet counts <100 × 109/L. In univariate and multivariate analyses, patients with low blast count on day 8 and high platelet count on day 33 were significantly associated with better EFS and OS. The combination of blast cell count on day 8 and platelet count on day 33 demonstrated a strong association with MRD-based risk stratification.Complete blood count is an inexpensive, easy to perform, and reliable measurement in children with ALL. The combination of blast count and platelet count during and after induction chemotherapy was a significant and independent prognostic factor for treatment outcome in pediatric ALL.
Topics: Adolescent; Biomarkers, Tumor; Blood Cell Count; Child; Child, Preschool; Female; Humans; Induction Chemotherapy; Infant; Infant, Newborn; Male; Platelet Count; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prognosis; Progression-Free Survival; Reproducibility of Results; Retrospective Studies; Treatment Outcome
PubMed: 33847682
DOI: 10.1097/MD.0000000000025548 -
Cancers Sep 2022Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk... (Review)
Review
Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk factors, the survival of acute lymphoblastic leukemia has significantly improved over the last decades. During the last years, measurable residual disease (MRD) assessment has evolved into one of the most sensitive markers for prognosis and risk of relapse. For this reason, measurable residual disease detection and monitoring count as standard evaluation in patients with acute lymphoblastic leukemia. Allogeneic stem cell transplantation is still the recommended treatment option for patients with high and highest risk profiles as well as for relapsed or refractory settings. The increased understanding of the pathomechanism and heterogeneity of acute lymphoblastic leukemia has led to the development of several novel therapeutic opportunities such as tyrosine-kinase inhibitors, antibody-based therapies and CAR-T cells with the aim of improving clinical outcomes. Furthermore, the major advances in disease understanding of ALL have led to the identification of different subgroups and better disease stratification. Even though novel therapy targets are constantly developed, acute lymphoblastic leukemia remains a challenging and life-threatening disease. To improve the historically unsatisfying result in therapy of adult acute lymphoblastic leukemia many clinical trials have recently been initiated to determine the optimum combination regimens of novel and old agents for adult acute lymphoblastic leukemia.
PubMed: 36077822
DOI: 10.3390/cancers14174290 -
Journal of Current Ophthalmology 2022To present primary ocular manifestations in acute leukemia.
PURPOSE
To present primary ocular manifestations in acute leukemia.
METHODS
This cross-sectional descriptive hospital-based study evaluated all newly diagnosed leukemia patients of three referral hospitals of Tehran University of Medical Sciences in 2015-2016 and Mahak Hospital in Tehran in 2017. Exclusion criteria included the patients with the previous history of chemotherapy, cases of relapsing disease, and the patients with a history of ocular disease or other systemic conditions with ophthalmic manifestations.
RESULTS
A total of 85 patients (170 eyes) were evaluated in our study, including 29 children (34.1%) and 43 females (50.6%). The mean patient age was 37.84 ± 11.91 years in the adult group and 6.28 ± 4.70 years in the pediatric category. Ophthalmic involvement was seen in 27 patients (31.8%), including 6 pediatric patients (20.7%) and 21 adult patients (37.5%). Two patients (2.3%) had direct infiltration by leukemic cells and 76 patients (89.41%) of patients were asymptomatic. There was a correlation between ophthalmic involvement and platelet count and hemoglobin level. In patients with ocular signs, higher mortality rates were observed.
CONCLUSIONS
At the time of diagnosis in acute leukemia patients, complete ophthalmic evaluation including dilated fundus examination is suggested as ocular involvement in these patients is common and sometimes asymptomatic. Ophthalmic involvement in leukemic patients should be identified in a timely manner, particularly in individuals with low platelet counts and hemoglobin levels, due to the potential prognostic relevance.
PubMed: 35620369
DOI: 10.4103/joco.joco_10_21 -
Cureus Jan 2022The clinical outcomes of CD34 and CD10 antigens expression in adolescent and young adult (AYA) precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) is not still...
Frequency of CD34 and CD10 Expression in Adolescent and Young Adult Patients Having Precursor B-cell Acute Lymphoblastic Leukemia and Its Correlation With Clinical Outcomes: A Single-Center Study.
BACKGROUND
The clinical outcomes of CD34 and CD10 antigens expression in adolescent and young adult (AYA) precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) is not still well established. In the present study, we analyzed the laboratory characteristics and clinical outcomes of 123 AYA pre-B-ALL patients in order to evaluate the possible clinical significance of these markers.
MATERIALS AND METHODS
In the current study clinical data of 123 consecutive AYA pre-B-ALL patients aged 18-39 years old, enrolled in adult hematology-oncology unit from December 2014 to April 2019 was analyzed. Patient clinical outcome was calculated as overall survival and disease-free survival.
RESULTS
Overall, 76.4% of patients showed CD34 expression and CD10 expression was found in 90.2%. CD34 and CD10 expression was associated with higher total leucocyte count, increased peripheral blood blast percentage, and decreased platelet count. Overall survival and disease-free survival were both significantly better in CD34 negative and CD10 negative patients compared to their CD34 positive and CD10 positive counterparts.
INTERPRETATION AND CONCLUSION
Expressions of CD34 and CD10 are adverse prognostic factors in AYA pre-B-ALL patients and the presence of these antigens influences the clinical outcome of these patients.
PubMed: 35178316
DOI: 10.7759/cureus.21261 -
JAMA Network Open Feb 2024COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and...
IMPORTANCE
COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes.
OBJECTIVE
To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy.
DESIGN, SETTING, AND PARTICIPANTS
This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period.
EXPOSURES
SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2.
MAIN OUTCOMES AND MEASURES
Description of the spectrum of COVID-19 illness and chemotherapy modifications.
RESULTS
Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021).
CONCLUSIONS AND RELEVANCE
In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.
Topics: Humans; Male; Child; Child, Preschool; Adolescent; Female; COVID-19; SARS-CoV-2; Retrospective Studies; COVID-19 Testing; Reinfection; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma
PubMed: 38363571
DOI: 10.1001/jamanetworkopen.2023.55727