scholarly journals Vincristine induced neurotoxicity in children who underwent chemotherapy for acute lymphoblastic leukemia and Wilms tumor

2021 ◽  
Vol 37 (5) ◽  
Author(s):  
Muhammad Kamran Adil ◽  
Zulfiqar Ali ◽  
Uzma Arshad ◽  
Usman Fawad
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Sampling Technique ◽  
Age Group ◽  
Creative Commons ◽  
Quasi Experimental ◽  
Chemotherapy Protocol ◽  
Open Access Article

Background & Objectives: Vincristine has been used as chemotherapeutic agent for many decades. It implements its function by inhibiting the duplication of tumor cells by destroying the DNA. However, like all other drugs, its administration is not without any side effects. The most important of these are being the neurotoxic side effects. This study evaluated the degree of neurotoxicity induced by vincristine in children who underwent chemotherapy for acute lymphoblastic leukemia and Wilms tumor. Methods: A quasi experimental study was conducted at Children Hospital & the Institute of Child Health, Multan from January 2020 to October 2020 after taking informed written consent. In this study, 150 children of age group 1—12 years with pathological confirmation of acute lymphoblastic leukemia and Wilms tumor who had undergone a chemotherapy protocol including at least four consecutive weekly Vincristine injections were included, using probability consecutive sampling technique. Neurological examination was conducted on them on weekly basis. Results: There were 150 patients,90(60%) males and 60(40%) females with mean age of (5.5±2.2). Diminished patellar and Achilles tendon reflexes were seen in 48% and 52% of patients. Muscular weakness was seen in 60% of patients. Other side effects like hoarseness, jaw pain, constipation and petosis were observed in 10%, 8%,40% and 10% of patients respectively. Frequency of side effects was equally observed in both sexes and it was more among age group older than five years (p= 0.01). Conclusion: Vincristine regimen produces some neurotoxic side effects in children but nearly all of these are of mild to moderate in nature. doi: https://doi.org/10.12669/pjms.37.5.4169 How to cite this:Adil MK, Ali Z, Arshad U, Fawad U. Vincristine induced neurotoxicity in children who underwent chemotherapy for acute lymphoblastic leukemia and Wilms tumor. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.4169 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Family history of early onset acute lymphoblastic leukemia is suggesting genetic associations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinjun Li ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Asta Försti ◽  
Kari Hemminki
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Statistical Significance ◽  
Age Groups ◽  
Age Group ◽  
Genetic Associations ◽  
Sequencing Data ◽  
Cancer Data ◽  
Group 5 ◽  
Prostate Cancers

AbstractChildhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0–4, 5–34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5–34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.

scholarly journals Somatic shift to homozygosity for a chromosomal polymorphism in a child with acute lymphoblastic leukemia

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 350-353 ◽  
Author(s):  
J Stamberg ◽  
A Shende ◽  
P Lanzkowsky
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Clinical Remission ◽  
Wilms Tumor ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Polymorphism ◽  
Chromosome 15 ◽  
General Importance ◽  
Tetrasomy 8

Abstract A 12-year-old girl with acute lymphoblastic leukemia (ALL) had two types of acquired cytogenetic abnormalities in her pretreatment peripheral blood and bone marrow: hyperdiploidy due to tetrasomy 8, 10, and 21; and, in the hyperdiploid cells, a shift from heterozygosity to homozygosity for a polymorphic variant on chromosome 15. Both abnormalities disappeared after chemotherapy, when the patient entered clinical remission. It has recently been found that shifts to homozygosity occur in retinoblastoma and Wilms' tumor. Our observation extends this finding to leukemia and indicates that such shifts may have general importance in tumorigenesis.

Time-Sequenced G-CSF (Lenograstim) for the Treatment of Adult Acute Lymphoblastic Leukemia - Seven Year Follow-Up of the Polish Adult Leukemia Group 4–96 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2733-2733
Author(s):  
Sebastian Giebel ◽  
Jerzy Holowiecki ◽  
Malgorzata Krawczyk-Kulis ◽  
Slawomira Kyrcz-Krzemien ◽  
Andrzej Hellmann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Chemotherapy Protocol ◽  
Adult Leukemia ◽  
Leukemia Group

Abstract The goal of the study was to evaluate long-term outcome of patients treated within 4–96 trial by the Polish Adult Leukemia Group (PALG). Sixty four patients with newly diagnosed acute lymphoblastic leukemia (ALL) (median age 26 years, range 16–58) were randomly assigned to receive chemotherapy alone (n=31) or chemotherapy and glucosylated G-CSF (lenograstim) (n=33). Both groups were well-balanced in terms of age, initial WBC, immunophenotype and bcr/abl positivity. Induction therapy consisted of epirubicin+vincristin (Epi/Vcr) on days 1, 8, 15, 22, prednisone on days 1–28, L-asparaginase 8 doses starting from day 13; consolidation treatment included twice methotrexate+etoposide (Mtx/Vep), twice high dose cytarabine and cyclophosphamide (HDAraC/Ctx), CNS irradiation and intrathecal Mtx. In T-derived ALL, additional HDAraC/Ctx was administered instead of the first Mtx/HDAraC. During induction patients received G-CSF 150 μg/m2 sc. on days 2–6, 9–13, 16–20, 23-until the neutrophil recovery >1.0x109/L, starting 36 hours after Epi/Vcr, finishing 48 hours before the next dose; in consolidation - following each HDAraC/Ctx course on days 5–16. High risk patients having a donor were performed allogeneic hematopoietic cell transplantation in first complete remission, whereas those without a donor were given autologous transplant. At seven years the overall survival rate equalled 42% for G-CSF group and 24% for the controls (p=0.11). There was also a trend to higher probability of leukemia-free survival in advantage of patients receiving the cytokine (38% vs. 20%, p=0.17). The above differences might have resulted from: 1) Higher CR rate in the G-CSF group compared to the controls (94% vs. 87%), 2) Better adherence to the chemotherapy protocol (faster completion of induction-consolidation programme by 19 days, p=0.005, less dose reductions or delays), which in turn might have influenced the risk of relapse. We conclude that time sequenced G-CSF administration may improve long-term outcome of adult ALL patients although the study including larger population is required to confirm this hypothesis.

Detection of Five Common Fusion Oncogenes in Pakistani Children with Acute Lymphoblastic Leukemia and Their Association with Clinical Pattern and Treatment Outcome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5124-5124
Author(s):  
Zafar Iqbal ◽  
Sabir Noreen ◽  
Aleem Aamer ◽  
Awan Tashfeen ◽  
Tahir Naeem ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
White Cell Count ◽  
Total Leukocyte Count ◽  
Age Group ◽  
Response To Chemotherapy ◽  
Pediatric All

Abstract Abstract 5124 Background & Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FGs) (Xu et al., 2012). The frequency of various FO can vary in different ethnic groups & these FGs have important implications for prognosis & treatment outcome (van-Dongen et al, 1999). Methods: We studied FGs in 101 pediatric ALL patients using Interphase FISH & RT-PCR (van-Dongen et al, 1999), & their association with clinical features & treatment outcome. Results: Five most common FGs i. e. BCR-ABL [t(9;22)], TCF3-PBX1 [t(1;19)], ETV6-RUNX1 [t(12;21)], MLL-AF4 [t(4;11)] & SIL-TAL1 (del 1p32) were found in 89/101 (88. 1%) patients. Frequency of BCR-ABL was 44. 5% (45/101) (Table 1). BCR-ABL positive patients had a significantly lower survival (43. 73 ± 4. 24 weeks) (Figure 1)& higher white cell count as compared to others except patients with MLL-AF4. The highest relapse-free survival (RFS) was documented in ETV6-RUNX1 (14. 167 months) followed closely by those cases in which no gene was detected (13/100). RFS in BCR-ABL, MLL-ASF4, TCF-PBX4 & SIL-TAL1 was less than 10 months (7. 994, 3. 559, 5. 500 & 8. 080 months respectively) (Figure 2 & 3). BCR-ABL: Frequency of occurrence was directly proportional to age (3 less than 2 year age group, 16 in the 2–7 year age group & 26 in the older than 7 group. Total leukocyte count (TLC) was higher when compared to patients with other oncogenes. Organomegaly was not common. BCR-ABL positivity was associated with low remission rates & shortened survival. ETV6-RUNX1: The median age of the patients was 1. 85 years. The gene frequency was highest in patients younger than 2 years. TLC was not very high & patients had a good prognosis. MLL-AF4: 17 patients had MLL-AF4 gene rearrangement with a median age of 9 years. Five patients were younger than 2 years, two between 2 & 7 years, & ten patients were in the 7–15 age group. Majority of our patients were older unlike the usual occurrence where most of the patients are infants. TCF3-PBX1: This FG occurs in around 2% of patients. Only two female patients were diagnosed with this translocation. Both the patients were over 2 years of age. It was associated with an inferior outcome in the context of response to chemotherapy & a higher risk of CNS relapse although small numbers preclude any firm conclusions. SIL-TAL1: Patients were older than 2 years, with the majority falling in the age range 7 to 15 years. The immunophenotype data were available in all SIL-TAL1 patients showing this fusion gene was associated with T-ALL with organomegaly being observed frequently. Discussion & Conclusion: This is the first study from Pakistan correlating molecular markers with disease biology & treatment outcome in pediatric ALL. Our study revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, in consistent with various other reports from Pakistan & rest of the world ((Iqbal & Akhtar, 2007; Faiz et al., 2011; (Gaynon et al., 1997; Iacobucci et al., 2012).) which, consequently, was associated with poor overall survival. The data indicates an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population & the development of facilities for stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

CITED2 Facilitates Apoptosis Induced By Histone Deacetylase Inhibitor SAHA In Human Pediatric Pre-B Acute Lymphoblastic Leukemia Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2913-2913
Author(s):  
Jinwei Du ◽  
Shigemi Matsuyama ◽  
Yu-Chung Yang
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Dependent Manner ◽  
Mouse Development ◽  
Childhood All ◽  
Normal Peripheral Blood

Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, representing 31% of all tumors, and about 85% of children with ALL have B-cell ALL. Although the survival rate is approaching 90%, ALL remains the main cause of death from disease in children and young adults. The activity of histone deacetylases (HDAC) in childhood ALL is increased compared with that in normal peripheral blood mononuclear cells or bone marrow cells. Treatment of mice engrafted with T or B-ALL cells with HDAC inhibitor (HDACi) increases the acetylation of Histone 3 and Histone 4 and prolongs survival of these mice. <>Vorinostat (Suberoylamilide Hydroxamic Acid, SAHA) was the first HDACi approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma. Currently, several clinical trials are being conducted to evaluate its effects on other cancers, including ALL. However, some patients are resistant to HDACi therapy, and concerns regarding toxic side effects of HDACi exist due to the roles of HDACs in multiple pathways. Therefore, identification of new therapeutic targets is required which could improve the efficacy of HDACi by reducing the dose of HDACi administered without compromising the treatment benefits but alleviating the side effects of HDACi. <>CBP/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)–rich tail 2 (CITED2) is a cytokine-inducible gene that plays various roles during mouse development and, in particular, is essential for normal hematopoiesis. While the role of CITED2 in the pathogenesis of leukemia is currently unclear, dysregulation of CITED2 has been implicated in various types of leukemia, including ALL, in which downregulation of CITED2 is frequently observed. In this study, we tested the hypothesis that CITED2 may enhance the sensitivity of human pediatric pre-B ALL cells to HDACi SAHA. <>SAHA treatment of NALM-6 and 697 cells (human pediatric pre-B ALL cell lines) significantly induced apoptosis and cell cycle arrest in a dose dependent manner. The protein level of CITED2 was not affected by SAHA treatment. Although overexpression of CITED2 alone only slightly increased apoptosis, it significantly enhanced apoptosis resulted from SAHA treatment in both NALM-6 (15.1% versus 39.2%) and 697 cells (9.4% versus 14.6%) as assessed by annexin V/Propidium Iodide double staining and flow cytometry analysis (Figure 1). Accordingly, compared with control (i.e. NALM-6 cells transduced with GFP), overexpression of CITED2 also greatly reduced mitochondrial membrane potential of NALM-6 cells caused by SAHA treatment. To explore the potential mechanisms underlying enhanced apoptosis by overexpression of CITED2 in NALM-6 cells treated with SAHA, we determined the levels of pro- and anti- apoptotic proteins by Western blot and real-time quantitative PCR. We found that SAHA treatment increased the levels of pro-apoptotic molecules Bak, Puma, and Noxa, and decreased the levels of anti-apoptotic molecule Bcl-xL and apoptosis inhibitors XIAP and survivin. Importantly, overexpression of CITED2 markedly increased the protein levels of pro-apoptotic molecules Bak and Bim. Furthermore, knockdown of Bim by shRNA significantly attenuated apoptosis in Cited2 overexpressing NALM-6 cells treated with SAHA. Taken together, these results suggest that modulation of the CITED2 activity may confer its cooperative effect with SAHA in pre-B ALL cells and warrant future evaluation of such a combination in inducing apoptosis of primary ALL cells. Disclosures: No relevant conflicts of interest to declare.

Aggravated Bone Density Decline after Symptomatic Osteonecrosis in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2260-2260
Author(s):  
Marissa den Hoed ◽  
S.M.F. Pluijm ◽  
Mariël L. Te Winkel ◽  
Hester A. de Groot-Kruseman ◽  
Marta Fiocco ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Bone Mineral ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Bone Destruction ◽  
Mineral Density ◽  
Pediatric All ◽  
Cessation Of Treatment

Abstract Background: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side effects can influence each other’s development during pediatric ALL treatment. Methods: BMD and the incidence of symptomatic ON were prospectively assessed in 466 patients with ALL (4-18 years of age) treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Symptomatic ON was defined as persistent pain in arms or legs not caused by vincristine administration, and confirmed by magnetic resonance imaging. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) were measured by dual X-ray absorptiometry at ALL diagnosis, after 32 weeks of treatment, at cessation of treatment (109 weeks) and 1 year after cessation of treatment. BMD was expressed as age-matched and gender-matched standard deviation scores (SDS; Z-score). Multivariate linear mixed models were adjusted for age at diagnosis. Results: Thirty patients (6.4%) suffered from ON. At cessation of treatment, mean BMDLS was -1.28 SDS (SD: 1.27, n=332; p<0.01) and BMDTB was -0.74 SDS (SD: 1.29, n=65; p<0.01) lower in ALL patients compared to their healthy peers. At baseline, BMDLS and BMDTB did not differ between patients who developed or who did not develop ON (mean BMDLS ON+: -0.90 vs. ON-: -1.14, p=0.36; mean BMDTB ON+: 0.07 vs. ON-: 0.25 p=0.65). At cessation of treatment, patients with ON seem to have a trend for a lower mean BMDLS (ON+: -1.68 vs. ON-: -1.31, p=0.18) and they have a lower mean BMDTB (ON+: -1.91 vs. ON-: -0.59, p=0.01) than patients without ON. Multivariate analyses showed that BMDTB change during follow-up was significantly different for patients with ON than without ON (interaction group time, p=0.04). Between BMD measurements before and after the diagnosis, patients with ON seemed to have a more rapid decline of BMDTB than in patients of the same age without ON (mean BMDTB difference -1.13 vs. -0.62, p=0.10). Conclusion: We conclude that symptomatic ON and low BMD during antileukemic treatment co-occur in pediatric ALL patients. BMD status at ALL diagnosis does not seem to precede ON. However, the development of ON seems to aggravate BMD decline during antileukemic treatment, most likely due to bone destruction and the advised physical immobilization. Disclosures No relevant conflicts of interest to declare.

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