PEG-asparaginase induced severe hypertriglyceridemia.

Thrombosis Prophylaxis with Apixaban in Patients Treated with Asparaginase

L-Carnitine Does Not Reduce Cytotoxicity from Induction Chemotherapy for Acute Lymphoblastic Leukemia

Asparagine Synthetase Expression and L-Asparaginase Sensitivity in Aggressive Lymphomas

Objective To explore the efficacy and safety of high-dose methotrexate (MTX) and L-asparaginase (L-Asp) for the treatment of adult patients with high risk Ph- acute lymphoblastic leukemia (ALL). Methods Five adult patients with high risk Ph- ALL were treated with several courses of MTX (3-5 g/m2 by continually intravenous drip for 24 h) and L-Asp (8 000-10 000 U/time, once a day, 10 times for one cycle). Results Five patients were disease-free survival, their survival time was 60-96 months and the median survival time was 73 months. The chemotherapy-related bone marrow depression was mild. No obvious liver and kidney damage, severe allergic reaction and pancreatitis were observed. Conclusion High-dose MTX and L-Asp are effective and well tolerated, and may contribute to long-term survival of adult patients with high risk Ph- ALL. Key words: Leukemia, lymphocytic, acute; Methotrexate; L-asparaginase; Long-term survival

Anthropometric measurements are considered a applicable and cost-effective indicator in primary healthcare settings for identifying the risk of obesity and related chronic diseases. This study aimed to elucidate the association between hypertriglyceridemia and neck circumference in adults. The participants diagnosed with hypertriglyceridemia (HTG) (n = 65) and those without HTG (n = 65) were assessed in this prospective case-control study. Measurements included body mass index, neck circumference (NC), waist circumference, hip circumference, and various metabolic laboratory parameters. The case group exhibited significantly higher anthropometric indices (body mass index, NC, waist circumference, and hip circumference) as well as higher age, fasting blood glucose, HbA1c, uric acid, hematocrit, hemoglobin, white blood cell count (WBC), low density lipid cholesterol, and triglyceride (TG) compared to the control group (p < 0.05). In the HTGsubgroup, the mean neck circumference was 38.1 ± 4.1cm, whereas in the control subgroup it was 35.7 ± 3.8cm, with a statistically significant difference between the two groups (p < 0.001). NC demonstrated statistically significant positive correlations with waist, hip circumference, and TG (r = 0.593, r = 0.461, r = 0.330, and r = 0.243, respectively; p < 0.001 for all). The regression analysis between NC and TG levels yielded a statistically significant model (p < 0.001), with the equation log(y) = 1.3423 + 0.02146x (R² = 0.150), suggesting that for each unit increase in NC, triglyceride concentration increases by approximately 2.1%. NC is closely associated with hypertriglyceridaemia in adults, while BMI, waist and hip circumference demonstrated a moderate positive correlation. Furthermore, a positive correlation with LDL-c and a negative correlation with HDL were also observed. What is already known about this topic? Anthropometric indices are simpleand low-cost quantitative measurements well positioned in primary health care, as they facilitate the early diagnosis of cardiometabolic diseases.Neck circumference is a simple, cost-effective and time-saving method to ascertain upper body obesity.Numerous studies have focused on the association between BMI, simple antropometric measurements and hypertension, or metabolic syndrome. However, there is little research investigating the primary effect of high triglycerides. However, few studies have investigated the primary effects of high triglyceride concentrations. 2.What this paper adds: This study demostrated an association between NC and non-HDL cholesterol levels esp. tryglicerid in adults. The study is expected to encourage clinicians using this cost-effective and easily applicable measurement method in clinical practice and to contribute to further research in this area.3.The implications of this paper: Health expenditure in developing countries should be used wisely, exam-based measurements should be preferred for less cost and efficiency focusing on prevention. Rather than frequent blood tests, primary health care services should promote easy body area measurements like neck circumference.

Combination of Dexamethasone and Asparaginase Induces Prothrombotic State in Children Receiving Multiagent Chemotherapy for Acute Lymphoblastic Leukemia

Minimal Residual Disease following Allogeneic Hematopoietic Stem Cell Transplantation

Objective To investigate the efficacy of modified VDLP (vincristine + daunorubicin + L-asparaginase + prednisone) for acute lymphoblastic leukemia (ALL) in elderly patients and its adverse reactions. Methods 31 elderly patients diagnosed as ALL at the initial visit from Jan. 2009 to Dec. 2014 were randomly divided into the experiment group (n=16) and the control group (n=15). Patients in the control group received traditional VDLP chemotherapy (vincristine 2 mg at 1, 8, 15 days; daunorubicin 30-40 mg/m2 at 1, 2, 15, 16 days; L-asparaginase 6 000-10 000 U at 11, 14, 17, 20 days; prednisone 1 mg/kg at 1 to 14 days), whereafter underwent a gradual dose reduction and drug withdrawal within 1-2 weeks. Patients in the experiment group received the modified VDLP chemotherapy (vincristine 2mg at 1, 8, 15 days; daunorubicin 30-40 mg/m2 at 1-3 days; L-asparaginase 6 000-10 000 U at 11, 14, 17, 20 days; prednisone 1 mg/kg at 1 to 14 days), whereafter underwent a gradual dose reduction and drug withdrawal within 1-2 weeks. The complete response (CR) rate and complications were recorded. Results The CR rates were 53.3% in modified VDLP group and 58.3% in VDLP group, and there was no statistically significant difference between two groups (P>0.05). The treatment-related mortality and the incidence of severe infection had significant differences between the modified VDLP and VDLP groups (6.3% vs. 46.3%, 31.3% vs. 66.7%, both P<0.05). Conclusions Compared with VDLP, the modified VDLP is more tolerable and suitable for the elderly patients with ALL. Key words: Antineoplastic Combined chemotherapy protocols; leukemia leukemia

Switch of Asparaginase Formulation Based on Antibody Monitoring in Adults with Philadelphia-Negative Adult Lymphoblastic Leukemia. Results of the Graall-2014 Trial

Autophagy intensity decreases in most blood malignancies, promoting cancer cell proliferation. Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are two main variants of leukemia. LC3, an important autophagy gene, and its protein, MAP1LC3B, precisely predict autophagy initiation and progression. The main objective of this systematic review is to investigate the correlation between changes in the expression of the LC3 gene in patients with ALL and AML. We performed a literature search in PubMed, Scopus, and Web of Science database in November 20, 2025, using the keywords and MeSH terms. All searches were restricted to sources in the English language, andwe focused on human case-control studies where definitive diagnosis was performed using hematological parameters. Initial identification included 1282 articles. Duplicates were removed, leaving 821 papers for screening. From these, 787 articles were removed for inappropriate titles and abstracts, leaving 34 for further review. Ultimately, 10 papers met the criteria for this systematic review. Five AML investigations demonstrated considerably lower LC3 gene expression than healthy controls. Downregulation was similar in one research. Upregulation was seen in two investigations. In two papers, ALL patients had considerably lower expression than healthy controls. Upregulation was significant in one study and non-significant in another one. The LC3 gene appears to be downregulated more consistently in AML, suggesting potential diagnostic or prognostic value. However, findings in ALL are inconsistent, and no definitive conclusion can be drawn. Further high-quality studies are required to clarify the role of LC3 in acute leukemias.

Morphometric properties of immature reticulocytes in health and during acute lymphoblastic and acute myeloid leukemia

Antibody deficiency may be a manifestation of primary immunodeficiency or can be generated by extrinsic factors. The frequency of secondary hypogammaglobulinemias has increased significantly in recent years in children with oncohematological pathology. Purpose — to study of clinical, biochemical and immunological indicators in children with secondary hypogammaglobulinemiae in order to determine management and treatment tactics. Materials and methods. 52 children with secondary hypogammaglobulinemiae were examined. Children were divided into 4 groups according to the primary diagnosis (acute myeloblastic, lymphoblastic leukemia and mixed phenotype leukemia, glomerulonephritis, nephrotic syndrome). Anamnesis and data of immunological (levels of serum immunoglobulins IgA, IgM, IgG, subpopulations of lymphocytes) evaluation prior to immunoglobulin replacement therapy. Results. Infectious diseases were observed in 22 children (42.3%). Allergic diseases occurred in 11 children (21%). Toxic complications of chemotherapy by internal organs and systems were found in 38 children (73%). Chronic kidney disease was diagnosed in 5 children (10%). The level of IgG was the lowest in children with nephrotic syndrome (2.6±1.54 g/l). The level of T lymphocytes — CD3+ (0.89±0.93x109/l) and T cytotoxic lymphocytes — CD3+CD8+ (0.33±0.38x109/l) were the lowest in the group of children with acute lymphoblastic leukemia. The level of T helper cells (CD3+CD4+) was low in the group of children with acute lymphoblastic (0.39±0.4x109/l) and myeloblastic leukemia (0.69±0.39x109/l). Level of B lymphocytes was low in the group of children with acute lymphoblastic (0.23±0.23x109/l) and myeloblastic leukemia (0), as well as in the group of children with nephrotic syndrome (0.18±0.13x109/l). Conclusions. Infectious diseases are common in children with secondary hypogammaglobulinemiae. In the group of children with acute leukemia bacterial and fungal diseases occurred more frequently and were more severe compared to the group of children with nephrotic syndrome. Therefore children with secondary hypogammaglobulinemia require control of serum immunoglobulin levels before starting immunosuppressive therapy, bone marrow transplantation and after its completion for the timely initiation of immunoglobulin replacement therapy in order to prevent infectious diseases and their complications. There is a need to determine serum antibody levels in children with nephrotic syndrome. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of a participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: secondary hypohammaglobulinemia, children, serum immunoglobulins, subpopulations of lymphocytes, nephrotic syndrome, proteinuria, acute leukemia.

Disclosure: S. Noguchi: None. A. Singh: None. A. Rajpal: None. Introduction: Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that has seen dramatic improvements in survival, owing to the development of multi-agent chemotherapy regimens. Pegaspargase (PEG), an enzyme that depletes serum asparagine and leads to apoptosis of leukemic cells, has long been a cornerstone of ALL chemotherapy regimens. While many toxicities have been recognized including hypersensitivity, thrombosis and hepatotoxicity, hypertriglyceridemia (HTG) is a much less documented complication. We present two patients who developed severe hypertriglyceridemia (sHTG) secondary to PEG, with differing outcomes. Both patients were re-challenged with PEG and again developed sHTG. Case description: A 31-year-old male presented with leukocytosis and blastemia and was diagnosed with Philadelphia chromosome negative B-cell ALL. He underwent chemotherapy induction via pediatric-inspired protocol CALBG 10403 which included PEG. Three weeks later triglyceride (TG) levels rose to 3,728 mg/dl, but normalized with gemfibrozil over the next month. He received two more doses of PEG, separated by four weeks, as part of consolidation chemotherapy. Eleven days following the third dose he presented with abdominal pain, lipase of 702 units/L, TG of 3,999 mg/dl and imaging consistent with necrotizing pancreatitis. With intravenous insulin and meropenem he eventually made a full recovery, however he had a persistent pancreatic pseudocyst. Thereafter, he was transitioned to HyperCVAD followed by POMP maintenance chemotherapy.Another patient, a 35-year-old female presented with cytopenia and was also diagnosed with Philadelphia chromosome negative B-cell ALL. She was also induced with CALBG 10403 protocol including PEG. One month later her TG levels rose to 1,295 mg/dl and was started on fenofibrate. Following resolution of the lipemia, she underwent consolidation chemotherapy which included two doses of PEG administered four weeks apart. Despite a 50% dose reduction, ten days after the third dose TGs rose to a peak of 3,363 mg/dl, however she did not develop pancreatitis. She was treated with intravenous insulin, gemfibrozil and omega-3-acid ethyl esters for sHTG. Given complications with CALGB, she is planned to transition to blinatumomab consolidation. Discussion: Albeit a rare complication of PEG, the presented cases highlight the severity of HTG that can result from this commonly used chemotherapy agent. There are currently no guidelines for the baseline assessment of TG levels in ALL patients receiving PEG. Awareness of this potential complication should prompt regular monitoring of TG levels in patients undergoing regimens involving PEG. There is a need for future studies to identify patients at higher risk of developing sHTG and evaluate the appropriate dose and frequency of PEG administration in patients who develop sHTG after initial exposure. Presentation: 6/3/2024

Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years. Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period. Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.

Objective To introduce the laboratory and clinical characteristics of acute lymphoblastic leukemia accompanied by the karyotypic abnormality of 5q-.Methods Report the diagnosis and treatment of one case of acute lymphoblastic leukemia with 5q- and review the relevant literatures.Results The patient came to the hospital because of bellyache and ostalgia.The blood routine showed a high WBC count and reduced platelets.Bone marrow aspirates examination indicated acute leukemia and by peroxidase staining and flow cytometry test,acute pro-T lymphoblastic leukemia was diagnosed.The karyotype and fluorescence in situ hybridization analysis showed 5q-.The hyper-CVAD regimen induced a temporary remission but it did not work anymore after the relapse nor did the MEA regimen.From the literatures ever reported,the kyryotypic abnormality of 5q- was rarely seen in acute lymphoblastic leukemia.In such cases,the minimal deletion region overlaped between marks of D5S410 and D5S436 corresponding to chromosomal location 5q31-33.Conclusion 5q- is rare in acute lymphoblastic leukemia and more features are still to be found about the kind of disorder. Key words: Leukemia biphenotypic, acute; Chromasome deletion