scholarly journals MARKERS OF ENDOTHELIAL DYSFUNCTION AND THEIR PROGNOSTIC VALUE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2020 ◽  
Vol 7 (1) ◽  
pp. 10-16
Author(s):  
Yu. Odinets ◽  
T. Kondratiuk ◽  
M. Koida
Keyword(s):  
Nitric Oxide ◽  
Acute Lymphoblastic Leukemia ◽  
Endothelial Dysfunction ◽  
Prognostic Value ◽  
Lymphoblastic Leukemia ◽  
Fatal Outcome ◽  
Cardiac Monitoring ◽  
Oxide Content ◽  
Healthy Children

MARKERS OF ENDOTHELIAL DYSFUNCTION AND THEIR PROGNOSTIC VALUE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA Y.V. Odinets, T.O. Kondratiuk, M.L. Koida Acute lymphoblastic leukemia (ALL) in children is associated with the development of a large number of serious complications. Inflammatory and pro-aggregation activation of endothelial cells accompanies the course of leukemia. Endothelial dysfunction (ED) is believed to be an integral part of the pathogenic link of ALL and its complications. Materials and methods. The content of nitric oxide in serum with the concentration of its stable metabolites - NO₂, NO₃ was determined in 73 patients with ALL and 19 healthy children. Determination of nitric oxide was performed at different stages of the presentation of ALL: 49 children were examined during the manifestation of leukemia (group 1A), of whom 36 children (group 1B) were re-examined during the first course of treatment – induction of remission. Also 8 children (group 2) were examined during supportive therapy and 16 children (group 3) who underwent complete chemotherapy treatment. Results. The study showed nitrite increases and nitrate reductions secondary to reduced total nitric oxide content during all treatment periods in children with ALL. In addition, signs of endothelial dysfunction were recorded in patients after treatment. ROC analysis showed that a reduction in NO₂ content lower than 12.31 µmol/l and a sum of NO₂ + NO₃ lower than 32.99 µmol/l significantly had a negative effect on the survival of children with ALL. Conclusions. ED accompanies the course of ALL in children. Determination of nitric oxide is of diagnostic and prognostic importance in patients with leukemia. The critical fall in the concentration of NO and NO₂ accompanies the development of multiple organ failure with fatal outcome in children with ALL. Preservation of signs of ED after the end of the treatment of leukemia indicates the need for cardiac monitoring of patients with ALL in history. Keywords: acute leukemia, children, endothelial dysfunction, nitric oxide Резюме. МАРКЕРИ ЕНДОТЕЛІАЛЬНОЇ ДИСФУНКЦІЇ ТА ЇХ ПРОГНОСТИЧНЕ ЗНАЧЕННЯ У ДІТЕЙ, ХІОРИХ НА ГОСТРУ ЛІМФОБЛАСТНУ ЛЕЙКЕМІЮ Ю.В. Одинець, Т.О. Кондратюк, М.Л. Койда. Гостра лімфобластна лейкемія (ГЛЛ) у дітей асоціюється з виникненням великої кількості тяжких ускладнень. Прозапальна та проагрегаційна активація ендотеліальних клітин супроводжує перебіг лейкемії. Вважається, що ендотеліальна дисфункція (ЕД) являються невід’ємливою частиною патогенетичної ланки ГЛЛ та її ускладнень. Mateріали та методи. Досліджено вміст оксиду азоту в сироватці крові за концентрацією його стабільних метаболітів – NO₂, NO₃ у 73 дітей, хворих на ГЛЛ та 19 здорових дітей. Визначення оксиду азоту проводили на різних етапах перебігу ГЛЛ: 49 дітей досліджено під час маніфестації лейкемії (група 1А), з них 36 дітей (група 1Б) повторно досліджено під час першого курсу лікування – індукції ремісії. Також 8 дітей (група 2) було досліджено під час проведення підтримуючої терапії і 16 дітей (група 3), які закінчили хіміотерапевтичне лікування. Результати. Ми отримали збільшення нітритів та зменшення нітратів на фоні зниженого загального вмісту оксиду азоту у продовж всіх періодів лікування та ремісії при ГЛЛ у дітей. Окрім того, ознаки ендотеліальної дисфункції фіксувались у хворих після закінчення лікування. ROC-аналіз продемонстрував, що  зниження вмісту NO₂ нижче ніж 12.31 мкмоль/л та суми NO₂+ NO₃ нижче, ніж 32.99 мкмоль/л  - достовірно впливає на негативний результат виживання дітей з ГЛЛ. Висновки. ЕД супроводжує перебіг ГЛЛ у дітей. Визначення оксиду азоту має діагностичну та прогностичну значущість у пацієнтів з лейкемією. Критичне падіння концентрації NO та NO₂ супроводжує виникнення поліорганної недостатності з летальним результатом у дітей, хворих на ГЛЛ.Збереження ознак ЕД після закінчення лікування у дітей, які перенесли ГЛЛ вказують на необхідність кардіологічного спостереження за даними хворими у катамнезі. Ключові слова: гостра лейкемія, діти, ендотеліальна дисфункція, оксид азоту   Резюме. МАРКЕРЫ ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИ И ИХ ПРОГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ У ДЕТЙ С ОТРОЙ ЛИМФОБЛАСТНОЙ ЛЕЙКЕМИЕЙ Ю.В. Одинец, Т.А. Кондратюк, М.Л. Койда. Острая лимфобластная лейкемия (ОЛЛ) у детей ассоциируется с возникновением значительного количества тяжелых осложнений. Провоспалительная и проагрегационная активация эндотелиальных клеток сопровождает течение лейкемии. При этом эндотелиальная дисфункция (ЭД) является неотъемлемой частью патогенеза ОЛЛ и ее осложнений. Материалы и методы. Исследовано содержание оксида азота в сыроватке крови по концентрации его стабильных метаболитов – NO₂, NO₃ у 73 детей с ОЛЛ и 19 здоровых детей. Определение оксида азота проводили на разных этапах протекания ОЛЛ: 49 детей иссследовано во время манифестации лейкемии (группа 1А), из них 36 детей (группа 1Б) повторно обследованы в течение первого курса терапии – индукции ремиссии. Также 8 детей (группа 2) были обследованы во время проведения поддерживающей терапии и 16 детей (группа 3), которые завершили химиотерапевтическое лечение. Результаты. Ми наблюдали увеличение нитритов и уменьшение нитратов на фоне сниженного общего содержания оксида азота в течение всех периодов лечения и ремиссии ОЛЛ у детей. Кроме того, признаки эндотелиальной дисфункции фиксировались у больных после окончания лечения. ROC-анализ проказал, что снижение содержание NO₂ ниже, чем 12.31 мкмоль/л и суммы NO₂+ NO₃ ниже 32.99 мкмоль/л  - достоверно влияет на неблагоприятный результат выживания детей с ОЛЛ. Выводы. ЭД сопровождает течение детской ОЛЛ. Определение оксида азота имеет диагностическое и прогностическое значение у пациентов с лейкемией. Критическое падение концентрации NO и NO₂ сопровождает возникновение полиорганной недостаточности с летальным результатом у детей, страдающих ОЛЛ. Сохранение признаков ЭД после завершения лечения у детей, перенесших ОЛЛ указывают на необходимость кардиологического наблюдения за данными пациентами в катамнезе. Ключевые слова: дети, эндотелиальная дисфунцкия, острая лейкемия, оксид азота

Relevance of Specific Immunoglobulin M and Immunoglobulin G for Parvovirus B19 Diagnosis in Patients With Acute Lymphoblastic Leukemia Receiving Chemotherapy: Prospective Study

2007 ◽  
Vol 131 (11) ◽  
pp. 1697-1699
Author(s):  
Maysaa El Sayed Zaki
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Acute Lymphoblastic Leukemia ◽  
Parvovirus B19 ◽  
Lymphoblastic Leukemia ◽  
Healthy Children ◽  
Immunocompromised Patients ◽  
Humoral Immune ◽  
Specific Immunoglobulin

Abstract Context.—Immunocompromised patients suffer from prolonged viral infections often without detectable immune response. However, even if the immune response occurs, can it clear the virus completely? Objective.—To detect parvovirus B19 DNA and its antibodies in bone marrow cells and in serum by polymerase chain reaction (PCR) in children with acute lymphoblastic leukemia receiving chemotherapy to highlight the relation of humoral immune response to the presence of viremia. Also, to evaluate the optimal diagnostic test(s) for a correct diagnosis of parvovirus B19 disease in immunocompromised patients. Design.—Forty-eight children with acute lymphoblastic leukemia receiving maintenance chemotherapy were included in the study in addition to 20 healthy children with matched age and sex. Study for parvovirus B19 was performed by serologic determination of specific immunoglobulin (Ig) M and IgG, and viral DNA was determined by PCR in both serum and bone marrow aspiration. Results.—Parvovirus B19 DNA was detected in both serum and bone marrow in 20% of patients. Specific IgG was found in 40% and IgM in 26.7%. Two cases (10%) in the control group were positive for IgG. The agreement between IgG and positive results of PCR in the bone marrow was 33.3%, and the agreement for IgM and PCR in the serum was 33.3%. Conclusions.—Parvovirus B19 is considered a common viral infection in children with acute lymphoblastic leukemia receiving chemotherapy. We must use our full potential to exclude such infection, which can mimic the side effects of chemotherapy in these patients. In immunocompromised patients, there are immunologic discrepancies in humoral immune responses for both IgM and IgG between individuals with parvovirus B19 persistence and healthy individuals, findings that may reflect both failed immunity and antigenic exhaustion. The contemporaneous determination of parvovirus B19 DNA by PCR in both bone marrow and peripheral blood and specific serologic markers appears to be the most appropriate diagnostic protocol for the correct laboratory diagnosis of parvovirus B19 infection in these patients.

scholarly journals Prognostic value of RASD1 transcript levels in adult Philadelphia-negative B-cell acute lymphoblastic leukemia

Hematology ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 9-15
Author(s):  
Run-Qing Lu ◽  
Li-Xin Wu ◽  
Jing Zhang ◽  
Ya-Zhen Qin ◽  
Yan-Rong Liu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Prognostic Value ◽  
Lymphoblastic Leukemia ◽  
Transcript Levels ◽  
Cell Acute Lymphoblastic Leukemia

Periodic Acid-Schiff Stain in Childhood Acute Lymphoblastic Leukemia: Lack of Independent Prognostic Value

1985 ◽  
Vol 83 (4) ◽  
pp. 494-497
Author(s):  
Gary R. Lanham ◽  
David K. Kalwinsky ◽  
Dorothy L. Williams ◽  
Susan L. Melvin ◽  
Jerry R. Harber ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Lymphoblastic Leukemia ◽  
Periodic Acid ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Periodic Acid Schiff

Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia

Leukemia ◽  
2021 ◽  
Author(s):  
Liv Andrés-Jensen ◽  
Kathrine Grell ◽  
Cecilie Utke Rank ◽  
Birgitte Klug Albertsen ◽  
Ruta Tuckuviene ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Endothelial Dysfunction ◽  
Lymphoblastic Leukemia ◽  
Adolescents And Young Adults

scholarly journals Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

2021 ◽  
Author(s):  
Runhong Yu ◽  
Shiwei Yang ◽  
Yufeng Liu ◽  
Zunmin Zhu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Western Blot ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Immunohistochemical Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Healthy Children ◽  
Expression Levels ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.

scholarly journals The Outcome of Children With Acute Lymphoblastic Leukemia Without Receiving Sufficient Dose of L-Asparaginase

2020 ◽  
Author(s):  
Gholamreza Bahoush ◽  
Gholamreza Bahoush ◽  
Marzieh Nojomi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hypersensitivity Reaction ◽  
Lymphoblastic Leukemia ◽  
Accurate Determination ◽  
Drug Regimen ◽  
Disease Recurrence ◽  
Free Survival ◽  
Complete Treatment

In acute lymphoblastic leukemia (ALL) patients treated with L-asparaginase, discontinuation of the drug occasionally occur due to severe drug complications or resistance, however, due to the high efficacy of this drug in the recovery of patients and the prevention of disease recurrence, resuming the drug regimen is preferred in most patients. What we did in this study was to evaluate and compare the effects of clinical outcomes in the two modes of continuing and discontinuing drug use. In this retrospective cohort study, all children with ALL who had been treated with L-asparaginase during the years 2005 to 2015 were included in the study and categorized into two groups receiving complete treatment regimen (n=160) and those who had to discontinue the drug due to appearing complications (n=9). The rate of relapse and mortality rate was determined and compared across the two groups with a median follow-up time of more than 5 years. 5-yrs Overall survival of all enrolled patients in the groups continued and discontinued was 91.4±2.5% and 71.4±17.1%, respectively (P=0.792). Also, 5-yrs event-free survival of the two groups was 75.8±3.5% and 71.4±17.1%, respectively (P=0.557. Relapse was revealed in 17.5% and 33.3% respectively and mortality in 16.9% and 0.0% (P=0.261). However, the overall prevalence of hypersensitivity reaction to the drug was significantly higher in those patients who discontinued their drug regimen (100% versus 24.4%, P<0.001). Hypersensitivity reaction to drugs may be an important factor in discontinuing L-asparaginase in patients with ALL. The discontinuation of L-asparaginase supplementation due to various complications such as hypersensitivity reactions may be effective in the survival of these patients. However, accurate determination of the effect of discontinuation of this drug on the outcome of children with ALL requires a more comprehensive study with more complicated cases.

scholarly journals Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1731-1737 ◽  
Author(s):  
A Manabe ◽  
E Coustan-Smith ◽  
M Kumagai ◽  
FG Behm ◽  
SC Raimondi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Programmed Cell Death ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Fatal Outcome ◽  
Interleukin 4 ◽  
B Lineage

Abstract We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.

scholarly journals The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

2015 ◽  
Vol 50 (4) ◽  
pp. 235 ◽  
Author(s):  
Ahmed M. L. Bedewy ◽  
Shereen M. EL-Maghraby ◽  
Noha S. Kandil ◽  
Waleed R. El-Bendary
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Glucocorticoid Receptors ◽  
Lymphoblastic Leukemia ◽  
Adult Acute Lymphoblastic Leukemia

scholarly journals Axitinib in Ponatinib-Resistant B-Cell Acute Lymphoblastic Leukemia Harboring a T315L Mutation

2020 ◽  
Vol 21 (24) ◽  
pp. 9724
Author(s):  
Valentina Giudice ◽  
Andrea Ghelli Luserna di Rorà ◽  
Bianca Serio ◽  
Roberto Guariglia ◽  
Maria Benedetta Giannini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Lymphoblastic Leukemia ◽  
Randomized Clinical Trials ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Fatal Outcome ◽  
Philadelphia Chromosome ◽  
Dose Finding ◽  
Third Generation

Adult acute lymphoblastic leukemia (ALL) with BCR-ABL1 rearrangement (Philadelphia chromosome, Ph) is a hematological aggressive disease with a fatal outcome in more than 50% of cases. Tyrosine kinase inhibitors (TKIs) targeting the activity of BCR-ABL1 protein have improved the prognosis; however, relapses are frequent because of acquired somatic mutations in the BCR-ABL1 kinase domain causing resistance to first, second and third generation TKIs. Axitinib has shown in vitro and ex vivo activity in blocking ABL1; however, clinical trials exploring its efficacy in ALL are missing. Here, we presented a 77-year-old male with a diagnosis of Ph positive ALL resistant to ponatinib and carrying a rare threonine to leucine (T315L) mutation on BCR-ABL1 gene. The patient was treated with axitinib at 5 mg/twice daily as salvage therapy showing an immediate although transient benefit with an overall survival of 9.3 months. Further dose-finding and randomized clinical trials are required to assess the real efficacy of axitinib for adult Ph positive ALL resistant to third generation TKIs.

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