Frequency and Aberrant CD Marker Profile of Acute Leukaemias.

OBJECTIVE: To determine the frequency of different types of acute leukaemia and their subtypes along with associated aberrant CD markers. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Immunology Armed Forces Institute of Pathology, National University of Medical Sciences, Rawalpindi, Pakistan, from November 2021 to October 2023. METHODOLOGY: All samples received for flow cytometric immunophenotyping with suspicion of acute leukaemia were included in the study. Cells were stained with fluorochrome labelled monoclonal antibodies against lineage-specific cluster of differentiation (CD) markers through a lyse-wash procedure. Acquisition and analysis were done using multi-parameter BD FACS Canto II Flow cytometer and BD FACS Diva software, respectively. Data were entered and analysed using SPSS v 23.0. RESULTS: Over a period of 2 years, a total of 1,115 suspected patients were tested for acute leukaemia. Among them, 728 (65.3%) were males and 387 (34.7%) were females, with mean age 28 ± 21 years, ranging from 1 week to 87 years. Among a total of 875/1115 (78.5%) diagnosed cases of acute leukaemia, AML was the most common leukaemia present in 408/875 (46.6%) patients followed by B-ALL and T-ALL in 384/875 (43.8%) and 70/87 (8%) patients, respectively (p = 0.5712). Aberrant CD markers were detected in 109/875 (12.5%) leukaemias (p = 0.0628). The most common aberrant CD markers in B-ALL were CD13 and CD33 present in 30/384 (7.8%) cases separately. Among AML and T-ALL most common aberrant CD markers were CD7 and CD33 present in 25/408 (6.13%) and 7/70 (10%) cases, respectively. CONCLUSION: Special consideration should be given to the presence of aberrant CD markers when assigning lineages to acute leukaemias. They may be important diagnostic, prognostic, and management tools for institution of immunotherapy. KEY WORDS: Aberrant CD markers, Acute leukaemia, CD Markers, Flow cytometry, Immunophenotyping.

Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

Impact of body mass index at diagnosis on outcomes of pediatric acute leukemia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood malnutrition i.e., both obesity and undernutrition, is on a rise. While there is extensive evidence of the influence of body mass index (BMI) on the survival and other important outcomes of adult cancers, the impact of childhood BMI on one of the common pediatric cancers i.e., leukemia is not well studied. METHODS: Systematic search of PubMed, Scopus, and Google Scholar databases was done to identify studies that were conducted among pediatric patients with leukemia and had examined outcomes of interest based on BMI at the time of diagnosis. RESULTS: Effect sizes were reported as pooled hazards ratio (HR) along with 95% confidence intervals (CI). A total of 17 studies were included. Compared to pediatric leukemia patients with normal BMI, underweight (HR 1.07, 95% CI: 1.04, 1.11) and obese (HR 1.42, 95% CI: 1.18, 1.71) children with leukemia had higher risks of overall mortality. Underweight (HR 1.10, 95% CI: 1.02, 1.19) and obese (HR 1.34, 95% CI: 1.15, 1.55) pediatric leukemia patients had a tendency to lower event-free survival compared to children with normal BMI. The risk of relapse was not significant for underweight, overweight, and obese children. CONCLUSIONS: Both underweight and obese status at the time of diagnosis were associated with poor survival outcomes in pediatric patients with leukemia.

Fmoc-FF hydrogels and nanogels for improved and selective delivery of dexamethasone in leukemic cells and diagnostic applications.

Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated. Peptide based HGs loaded with DEX were formulated via the "solvent-switch" method, using Fmoc-FF homopeptide as building block. Due to the tight interaction of the drug with the peptidic matrix, a significant stiffening of the gel (G' = 67.9 kPa) was observed. The corresponding injectable NGs, obtained from the sub-micronization of the HG, in the presence of two stabilizing agents (SPAN®60 and TWEEN®60, 48/52 w/w), were found to be stable up to 90 days, with a mean diameter of 105 nm. NGs do not exhibit hemolytic effects on human serum, moreover they are selectively internalized by RS4;11 leukemic cells over healthy PBMCs, paving the way for the generation of new diagnostic strategies targeting onco-hematological diseases.

Leukemia cancer cells and immune cells derived-exosomes: Possible roles in leukemia progression and therapy.

Exosomes have a significant impact on tumor survival, proliferation, metastasis, and recurrence. They also open up new therapeutic options and aid in the pathological identification and diagnosis of cancers. Exosomes have been shown in numerous studies to be essential for facilitating cell-to-cell communication. In B-cell hematological malignancies, the proteins and RNAs that are encased by circulating exosomes are thought to represent prospective sources for therapeutic drugs as well as biomarkers for diagnosis and prognosis. Additionally, exosomes can offer a "snapshot" of the tumor and the metastatic environment at any given point in time. In this review study, we concluded that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. Moreover, clinical studies have demonstrated that immune cells like dendritic cells create exosomes, which have the ability to activate the immune system against leukemia.

Application of droplet digital PCR in minimal residual disease monitoring of rare fusion transcripts and mutations in haematological malignancies.

Leukaemia of various subtypes are driven by distinct chromosomal rearrangement or genetic abnormalities. The leukaemogenic fusion transcripts or genetic mutations serve as molecular markers for minimal residual disease (MRD) monitoring. The current study evaluated the applicability of several droplet digital PCR assays for the detection of these targets at RNA and DNA levels (atypical BCR::ABL1 e19a2, e23a2ins52, e13a2ins74, rare types of CBFB::MYH11 (G and I), PCM1::JAK2, KMT2A::ELL2, PICALM::MLLT10 fusion transcripts and CEBPA frame-shift and insertion/duplication mutations) with high sensitivity. The analytical performances were assessed by the limit of blanks, limit of detection, limit of quantification and linear regression. Our data demonstrated serial MRD monitoring for patients at molecular level could become "digitalized", which was deemed important to guide clinicians in treatment decision for better patient care.

What Is Childhood Leukemia?

This JAMA Patient Page outlines the symptoms, diagnosis, and treatment of childhood leukemia.

Epidemiology and prognostic nomogram for chronic eosinophilic leukemia: a population-based study using the SEER database.

Chronic Eosinophilic Leukemia (CEL), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate epidemiology and develop a prognostic nomogram for CEL patients. Utilizing the Surveillance, Epidemiology and End Results database, CEL cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL patients by incorporating these factors. The incidence rate of CEL was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL as independent and adverse predictors of overall survival. To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups. This study enhances our understanding of CEL, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL.

[Suspicion of constitutional abnormality at diagnosis of childhood leukemia: Update of the leukemia committee of the French Society of Childhood Cancers]. / Suspicion d'anomalie constitutionnelle au diagnostic de leucémie chez l'enfant : mise au point du comité leucémies de la Société française des cancers de l'enfant.

The spectrum of childhood leukemia predisposition syndromes has grown significantly over last decades. These predisposition syndromes mainly involve CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, RAS-MAPK pathway, DNA mismatch repair system genes, genes associated with Fanconi anemia, and trisomy 21. The clinico-biological features leading to the suspicion of a leukemia predisposition are highly heterogeneous and require varied exploration strategies. The study of the initial characteristics of childhood leukemias includes high-throughput sequencing techniques, which have increased the frequency of situations where a leukemia predisposing syndrome is suspected. Identification of a leukemia predisposition syndrome can have a major impact on the choice of chemotherapy, the indication for hematopoietic stem cell transplantation, and screening for associated malformations and pathologies. The diagnosis of a predisposition syndrome can also lead to the exploration of family members and genetic counseling. Diagnosis and management should be based on dedicated and multidisciplinary care networks.

Acute undifferentiated leukemia with undifferentiated myeloid sarcoma: Case report and literature review.

BACKGROUND: With the advancement of diagnostic technology, true acute undifferentiated leukemia (AUL) is becoming more rare, and AUL with extramedullary sarcoma has not been reported. CASE PRESENTATION: This article reports a case of AUL with extramedullary sarcoma. Flow cytometric analysis of the bone marrow and lymph nodes indicated that the tumor cells of both were of the same origin and mainly expressed stem cell markers and CD7, no myeloid-specific markers, T-lymphoblastic-related markers, and B-lymphoblastic-related markers. Although the priming regimen combined with azacitidine was ineffective, complete remission was achieved by switching to azacitidine combined with HIA (homoharringtonine, idarubicin plus Ara-C). CONCLUSION: To diagnosis de novo acute leukemia with extensive and comprehensive cellular immune maker detection is available and credible, the expression of a single relatively nonspecific myeloid antigen as a immune maker to detect AUL or AUL associated with sarcoma is precise and effective in our case, which patient was benefit from HIA regiment.

The Gut Microbiome and Acute Leukemia: Implications for Early Diagnostic and New Therapies.

Acute leukemia (AL), one of the hematological malignancies, shows high heterogeneity. Tremendous progresses are achieved in treating AL with novel targeted drugs and allogeneic hematopoietic stem cell transplantation, there are numerous issues including pathogenesis, early diagnosis, and therapeutic efficacy of AL to be solved. In recent years, an increasing number of studies regarding microbiome have shed more lights on the role of gut microbiota in promoting AL progression. Mechanisms related to the role of gut microbiota in enhancing AL genesis are summarized in the present work, especially on critical pathways like leaky gut, bacterial dysbiosis, microorganism-related molecular patterns, and bacterial metabolites, resulting in AL development. Additionally, the potential of gut microbiota as the biomarker for early AL diagnosis is discussed. It also outlooks therapies targeting gut microbiota for preventing AL development.

Use, variability, and justification of eligibility criteria for phase II and III clinical trials in acute leukemia.

Clinical trial eligibility criteria can unfairly exclude patients or unnecessarily expose them to known risks if criteria are not concordant with drug safety. There are few data evaluating the extent to which acute leukemia eligibility criteria are justified. We analyzed criteria and drug safety data for front-line phase II and/or III acute leukemia trials with start dates 1/1/2010-12/31/2019 registered on clinicaltrials.gov. Multivariable analyses assessed concordance between criteria use and safety data (presence of criteria with a safety signal, or absence of criteria without a signal), and differences between criteria and safety-based limits. Of 250 eligible trials, concordant use of ejection fraction criteria was seen in 34.8%, corrected QT level (QTc) in 22.4%, bilirubin in 68.4%, aspartate transaminase/alanine aminotransferase (AST/ALT) in 58.8%, renal function in 68.4%, human immunodeficiency virus (HIV) in 54.8%, and hepatitis B and C in 42.0% and 41.2%. HIV and hepatitis B and C criteria use was concordant with safety data (adjusted Odds Ratios 2.04 [95%CI: 1.13, 3.66], 2.64 [95%CI: 1.38, 5.04], 2.27 [95%CI: 1.20, 4.32]) but organ function criteria were not (all P>0.05); phase III trials were not more concordant. Bilirubin criteria limits were the same as safety-based limits in 16.0% of trials, AST/ALT in 18.1%, and renal function in 13.9%; in 75.7%, 51.4%, and 56.5% of trials, criteria were more restrictive, respectively, by median differences of 0.2, 0.5, and 0.5 times the upper limits of normal. We found limited drug safety justifications for acute leukemia eligibility criteria. These data define criteria use and limits that can be rationally modified to increase patient inclusion and welfare.

Acute leukemias and complicated lymphomas: pearls to optimize management when patients stay local.

Hematologic malignancies often present acutely with a constellation of infectious complications, pancytopenia, tumor lysis, and renal dysfunction. Acute leukemias and aggressive lymphomas often require hospitalization for rapid diagnostic evaluation, urgent management of complicating presentations, and timely management of intensive systemic therapies. There is an emerging paradigm whereby complex cancer care can be safely and effectively provided in the community, where the majority of cancer is treated. A substantive and effective network between local oncologists and their academic counterparts will enhance care for the patient, advance research, and help bring complicated therapies to local centers, thereby improving access. Here we present several cases that highlight a collaborative approach to complicated hematologic malignancies in the community.

Comparison of methods to testing for differential treatment effect under non-proportional hazards data.

Many tests for comparing survival curves have been proposed over the last decades. There are two branches, one based on weighted log-rank statistics and other based on weighted Kaplan-Meier statistics. If we carefully choose the weight function, a substantial increase in power of tests against non-proportional alternatives can be obtained. However, it is difficult to specify in advance the types of survival differences that may actually exist between two groups. Therefore, a combination test can simultaneously detect equally weighted, early, late or middle departures from the null hypothesis and can robustly handle several non-proportional hazard types with no a priori knowledge of the hazard functions. In this paper, we focus on the most used and the most powerful test statistics related to these two branches which have been studied separately but not compared between them. Through a simulation study, we compare the size and power of thirteen test statistics under proportional hazards and different types of non-proportional hazards patterns. We illustrate the procedures using data from a clinical trial of bone marrow transplant patients with leukemia.

Nanotechnology in leukemia: diagnosis, efficient-targeted drug delivery, and clinical trials.

Leukemia is a group of malignant disorders which affect the blood and blood-forming tissues in the bone marrow, lymphatic system, and spleen. Many types of leukemia exist; thus, their diagnosis and treatment are somewhat complicated. The use of conventional strategies for treatment such as chemotherapy and radiotherapy may develop many side effects and toxicity. Hence, modern research is concerned with the development of specific nano-formulations for targeted delivery of anti-leukemic drugs avoiding toxic effects on normal cells. Nanostructures can be applied not only in treatment but also in diagnosis. In this article, types of leukemia, its causes, diagnosis as well as conventional treatment of leukemia shall be reviewed. Then, the use of nanoparticles in diagnosis of leukemia and synthesis of nanocarriers for efficient delivery of anti-leukemia drugs being investigated in in vivo and clinical studies. Therefore, it may contribute to the discovery of novel and emerging nanoparticles for targeted treatment of leukemia with less side effects and toxicities.

Meta-analysis of the Prognostic Value of microRNA-22 in Leukemia Patients.

Objective: The pathogenesis of leukemia is complex and there are no effective diagnostic and prognostic indicators. Previous studies showed that microRNA-22 (miR-22) has altered expression level in multiple leukemia subtypes, which is associated with the survival outcomes of leukemia. Methods: According to the constituted retrieval strategy, eligible studies were included from January 2010 to November 2022 by searching database. The pooled Risk Ratio (RR) and 95% confidence intervals (CI) were used to study the relationship between miR-22 and survival. Stata12.0 was used for meta-analysis. Differential expression analysis was conducted based on expression profile of miRNA. Results: Four English articles were included containing a total of 215 leukemia patients. Data showed that the pooled RR for overall survival (OS) was 1.558 (95% CI: 1.197-2.028, P < .01). Subgroup analysis for OS of acute myeloid leukemia patients and the RFS of plasma cell leukemia patients were statistically significant with different expression levels of miR-22 (RR:1.495, 95%CI:1.141-1.958, P < .01 and RR:1.517, 95%CI:1.114-2.065, P < .01, respectively). Moreover, all data included had no significant heterogeneity and publication bias. Conclusions: miR-22 is associated with the survival outcome of leukemia patients suggesting that miR-22 may be a promising prognostic biomarker for this patient population, and the expression level of miR-22 in ALL patients down-regulated.