scholarly journals Clinico-epidemiological features and response in childhood acute lymphoblastic leukemia at regional cancer center of Northeast India

2019 ◽  
Vol 08 (04) ◽  
pp. 241-243
Author(s):  
Bhargab Jyoti Saikia ◽  
Partha Sarathi Roy ◽  
Gaurav Kumar ◽  
Rakesh Kumar Mishra ◽  
Anupam Sarma
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Northeast India ◽  
Cancer Center ◽  
Childhood Cancers ◽  
Related Factors ◽  
Childhood All ◽  
The Common ◽  
Cure Rates

Abstract Introduction: Acute lymphoblastic leukemia (ALL) comprises 19.3% of all childhood cancers in Northeast India. Methods: We analyzed clinicoepidemiological features and early response to the treatment of all the cases of childhood ALL (age <15 years) diagnosed and treated at Dr. B Borooah Cancer Institute over 1 year. Results: Of 52 eligible cases, 69% were male (male:female ratio of 2.2:1) and the mean age was 7.1 years. Thirty-three children (63%) had baseline white blood cell count ≥20 × 109/L. Precursor B-cell was most the common subtype seen in 61% of children. Seven cases (14%) had high-risk (HR) cytogenetics, with t (9,22) being the most common one. Male sex and HR cytogenetics were significantly associated with poor early responses. Conclusion: ALL is a common childhood malignancy with high cure rates. However, poor socioeconomic status and the presence of higher proportions of disease-related factors lead to poor outcome in this part of the country.

scholarly journals Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 66-70
Author(s):  
T Mohanakumar ◽  
TW Coffey ◽  
MP Vaughn ◽  
EC Russell ◽  
D Conrad
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Membrane Component ◽  
Childhood All ◽  
Antigen Present ◽  
The Common ◽  
Blood Elements ◽  
Human Primate

Abstract A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.

scholarly journals Characterization of non-human primate antisera to acute lymphoblastic leukemia (ALL): evidence for unique antigen(s) on childhood ALL of "T" phenotype

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 66-70
Author(s):  
T Mohanakumar ◽  
TW Coffey ◽  
MP Vaughn ◽  
EC Russell ◽  
D Conrad
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Membrane Component ◽  
Childhood All ◽  
Antigen Present ◽  
The Common ◽  
Blood Elements ◽  
Human Primate

A non-human primate antiserum was prepared to acute lymphoblastic leukemia of T-cell phenotype (T-ALL) and, after absorptions with normal blood elements, reacted by immunofluorescence and microcytotoxicity to all the T-ALL tested. In addition, the antiserum reacted with cells from about 70% of the common ALL studied and immunoprecipitated the common ALL antigen of 100,000 daltons. However, when the anti-T-ALL serum was absorbed with with lymphoblasts from common ALL, it failed to react with common ALL lymphoblasts, yet reacted significantly with cells from patients with T-ALL phenotype and defined a 100,000-dalton membrane component not found on common ALL lymphoblasts. In addition, sequential immunoprecipitation of 125I-labeled T-ALL membranes by anti- common-ALL serum followed by anti-T-ALL serum detected the T-ALL membrane component of 100,000 daltons that was not found on common ALL. Thus, our results demonstrate the presence of of a unique human T-ALL antigen present on all T-ALL distinct from the common ALL antigen.

scholarly journals Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3769-3777 ◽  
Author(s):  
Fatih M. Uckun ◽  
Zhiwen Yang ◽  
Harland Sather ◽  
Peter Steinherz ◽  
James Nachman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Leukemic Cells ◽  
Small Subset ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Childhood All ◽  
Free Survival ◽  
Cellular Expression

Abstract We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.

Germ-Line Genetic Variations in TP53 and Risk for Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1890-1890
Author(s):  
Toralf Bernig ◽  
Laurie Burdette ◽  
Thomas Lehrnbecher ◽  
Ulrike B. Graubner ◽  
Monique L. den Boer ◽  
...  
Keyword(s):  
At Risk ◽  
Genetic Variation ◽  
Acute Lymphoblastic Leukemia ◽  
Tumor Suppressor ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Risk Haplotype ◽  
Childhood All ◽  
Increased Risk ◽  
The Common

Abstract The tumor suppressor p53 plays an essential role in the prevention of tumor development by its ability to respond to stress signals, resulting in the inhibition of cell growth, via cell-cycle arrest or induction of apoptosis. p53 also contributes to the repair of genotoxic DNA damages and is involved in cellular senescence. Previous studies have shown that both germ-line and somatic mutations in the TP53 gene, which encodes p53, can occur in a wide spectrum of cancers, including acute lymphoblastic leukemia, ALL. Recently, we characterized the common germ-line genetic variation across TP53 by extensive re-sequence analysis (http://snp500cancer.nci.nih.gov). Patients and Methods: We conducted a genetic association study in childhood ALL to investigate the possible contribution of common single nucleotide polymorphisms, SNPs, and the common haplotypes on which they reside. For TP53, we analyzed haplotype-tagging SNPs, which are estimated to capture greater than 95% of common haplotypes across the gene (IVS2+38C, Ex4+119 (R72P), IVS4-91, Ex6-34 (R213R), IVS6+62, IVS6-36 and 1846bp 3′ of STP). Cases of ALL (n = 513) were drawn from anonymized samples from the German co-operative therapy study (COALL-06-97) and 751 healthy anonymized blood donor controls collected from regional blood banks in Germany. Genotype analysis was performed by validated Taqman assays posted on the SNP500cancer website. Haplotypes were deduced by maximization-estimation analysis of unphased genotypes using PHASEv2.0.1 (http://www.stat.washington.edu/stephens/software.html). Results: The single locus analysis revealed an increased risk for ALL for four of the seven SNPs individually: C allele at IVS2+38C (304/982 in patients vs. 399/1476 in controls, OR 1.21 95% CI 1.01 – 1.45), G allele at IVS4-91 (150/988 vs. 168/1456, OR 1.37 95% CI 1.08 – 1.75), A allele at Ex6-34 (R213R) (164/996 vs. 178/1450, OR 1.41 95% CI 1.11 – 1.78) and T allele at 1846bp 3′ of STP (185/990 vs. 203/1420, OR 1.38 95% CI 1.10 – 1.72). Individuals homozygous AA at IVS6+62 (16/350 vs. 9/556, OR 2.82, 95% CI 1.16 – 6.99) or TT at 1846bp 3′ of STP (24/334 vs. 15/522 OR 2.50, 955 CI 1.24 – 5.09) showed further risk for disease. The non-synonymous coding SNP at Ex4+119 (R72P) did not show any association with ALL. The distribution of the inferred haplotypes differed significantly between cases and controls (global haplotype test p = 0.02). Children carrying the haplotype CCGAAGT have an increased risk for ALL (138/611 vs. 155/972, OR 1.42, 95% CI 1.09 −1.83) in reference to the most common haplotype GGAAGGC. Conclusions: Our data suggest that susceptibility to pediatric ALL could be associated with at least one copy of an “at risk” haplotype. The study results imply that germ-line genetic variation in TP53, a key tumor suppressor gene, could contribute to susceptibility to childhood ALL. Additional studies are required to confirm our findings and to characterize the functional elements in the at-risk haplotypes.

The Outcome of Children with T-Cell Acute Lymphoblastic Leukemia: A Single Institution Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4526-4526
Author(s):  
Ali Al-Ahmari ◽  
Asim F. Belgaumi ◽  
Abdelmuniem Al-Dalee ◽  
Mohammed Al-Mahr ◽  
Abdulrahman Al-Musa ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Mediastinal Mass ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Current Treatment ◽  
High Dose ◽  
Childhood All ◽  
Number Of Patients ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Background: T-cell acute lymphoblastic leukemia (T-ALL) constitutes 10% to 15 % of childhood ALL cases in the Western literature. However, higher proportions, up to 40%, have been reported in certain developing countries. While the outcome of childhood T-ALL has improved dramatically over the last decades, by using intensive multi-agent chemotherapeutic regimens, about 30% to 40% of these patients still experience relapses. Patients and methods: Medical records of the 411 pediatric patients (0–13 years old) diagnosed with ALL and treated at our institution between January 1999 and December 2004 were retrospectively reviewed. Result: Fifty-three (12.9%) of the patients had T-ALL. 52 of these were treated according to a multi-drug chemotherapy protocol, based on a modification of the St. Jude Total XIII-B protocol, including high-dose methotrexate (HD-MTX), at 2gm/m2, and non-cross-resistant drug pair administered weekly during the continuation phase. The remaining one patient received a standard ALL therapy with a single delayed intensification and anti-metabolite based maintenance therapy. Early response to induction chemotherapy was assessed using a bone marrow (BM) evaluation at Day-14 of induction. The mean age was 7.1 years and 36 patients (68%) were males. Twenty (39%), out of 51 patients with available results, had CNS involvement. Of these eight (15.5%) were categorized as CNS-3, while 12 (23.5%) were CNS-2. 50% of the patients presented with mediastinal mass. Nine (18%) of the patients with available initial WBC (n=49) had hyperleukocytosis with a WBC &gt;100 × 109/L. 8 out of the 51 patients with a Day-14 evaluation had &gt;5% blasts in the BM. All patients subsequently achieved remission at the end of induction. The 5-year event-free survival (EFS) and overall survival (OS) rates were 63.9% and 76.4%, respectively. 13 (24.5%) patients relapsed at a median time of one year. Six relapses occurred in the BM, 5 isolated-CNS relapses, one CNS+BM and one in the skin+BM. Only 2 of these relapsed patients are long-term survivors. The disease-related and treatment toxicity-related deaths occurred in 11(20.7%) and 2(3.7%) patients, respectively. The initial WBC count, mediastinal mass, CNS status or the Day-14 BM results were not found to impact negatively on the outcome, by multivariate analysis. Conclusion: Our current treatment strategy has resulted in potential cure for about two-thirds of the patients with childhood T-ALL. However, a significant number of patients do fail treatment and novel strategies need to be devised for them. Unfortunately, as specific clinical features that could determine outcome have not as yet been identified, risk stratification, similar to that utilized for precursor-B cell ALL, is not feasible. Further study into risk determining variables at the molecular level, such as activating NOTCH1 mutations, may be promising in predicting outcome and determining treatment intensity in children with T-ALL.

scholarly journals Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study

Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3769-3777 ◽  
Author(s):  
Fatih M. Uckun ◽  
Zhiwen Yang ◽  
Harland Sather ◽  
Peter Steinherz ◽  
James Nachman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Leukemic Cells ◽  
Small Subset ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Childhood All ◽  
Free Survival ◽  
Cellular Expression

We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.

Preferential loss of maternal 9p alleles in childhood acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 375-377 ◽  
Author(s):  
Ian M. Morison ◽  
Lana M. Ellis ◽  
Lochie R. Teague ◽  
Anthony E. Reeve
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genomic Imprinting ◽  
High Frequency ◽  
Germ Line ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Parental Origin ◽  
Childhood Cancers ◽  
Childhood All ◽  
Preferential Loss

Germ-line events, such as paternal mutation or genomic imprinting, contribute to the early onset of childhood cancers such as retinoblastoma, Wilms tumors, and neuroblastoma. Given the high frequency of deletion involving chromosome 9p in childhood acute lymphoblastic leukemia (ALL), this study investigated whether 9p deletion might reflect preexisting germ-line gene inactivation. To do this the parental origin of deletion was determined in 10 cases of ALL with 9p21 loss of heterozygosity. Of these cases, 9 showed loss of the maternally derived allele, suggesting that a germ-line event involving a 9p gene may play a role in the onset of childhood ALL.

scholarly journals Chemotherapy Delays Are Associated with Inferior Outcome in Acute Lymphoblastic Leukemia: A Retrospective Study from a Tertiary Cancer Center in South India

2021 ◽  
Vol 42 (01) ◽  
pp. 051-060
Author(s):  
Vineet Agrawal ◽  
Smita Kayal ◽  
Prasanth Ganesan ◽  
Biswajit Dubashi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Survival Outcomes ◽  
Separate Analysis ◽  
Term Survival ◽  
Free Survival ◽  
Intensive Phase ◽  
The Impact

Abstract Background Treatment protocols for acute lymphoblastic leukemia (ALL) have evolved over time to give excellent cure rates in children and moderate outcomes in adults; however, little is known how delays in chemotherapy affect long-term survival. Objectives To find the association of delays during different treatment phases on the survival outcomes. Materials and Methods Data from 149 ALL cases treated between 2009 and 2015 were retrospectively analyzed. Treatment course in commonly used protocols was divided into three phases—induction, consolidation (postremission), maintenance, and also a combined intensive phase (induction plus consolidation) for the purpose of analysis, and delay in each phase was defined based on clinically acceptable breaks. Analysis was done to find the impact of treatment delay in each phase on the survival outcomes. Results The median age was 12 years (range, 1–57). Multi-center Protocol-841 (MCP-841) was used for 72%, German Multicenter Study Group for Adult ALL (GMALL) for 19%, and Berlin, Frankfurt, Muenster, 95 protocol (BFM-95) for 9% of patients. Delay in induction was seen in 52%, consolidation in 66%, and during maintenance in 42% of patients. The median follow-up was 41 months, and 3-year survival outcomes for the entire cohort were event-free survival (EFS)—60%, relapse-free survival (RFS)—72%, and overall survival (OS)—68%. On univariate analysis, delay in induction adversely affected EFS (hazard ratio [HR] = 1.78, p = 0.04), while delay in intensive phase had significantly worse EFS and RFS (HR = 2.41 [p = 0.03] and HR = 2.57 [p = 0.03], respectively). On separate analysis of MCP-841 cohort, delay in intensive phase affected both EFS (HR = 3.85, p = 0.02) and RFS (HR = 3.42, p = 0.04), whereas delay in consolidation significantly affected OS with (HR = 4.74, p = 0.04) independently. Conclusion Treatment delays mostly in intensive phase are associated with worse survival in ALL; attempts should be made to maintain protocol-defined treatment intensity while adequately managing toxicities.

scholarly journals Inhibition of Autophagy Enhances the Antitumor Effect of Thioridazine in Acute Lymphoblastic Leukemia Cells

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 365
Author(s):  
Carina Colturato-Kido ◽  
Rayssa M. Lopes ◽  
Hyllana C. D. Medeiros ◽  
Claudia A. Costa ◽  
Laura F. L. Prado-Souza ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Clinical Problem ◽  
Jurkat Cells ◽  
Leukemia Cells ◽  
Peripheral Mononuclear Blood ◽  
Induced Apoptosis ◽  
Cure Rates

Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells that affects children and adults. Despite the high cure rates, drug resistance still remains a significant clinical problem, which stimulates the development of new therapeutic strategies and drugs to improve the disease outcome. Antipsychotic phenothiazines have emerged as potential candidates to be repositioned as antitumor drugs. It was previously shown that the anti-histaminic phenothiazine derivative promethazine induced autophagy-associated cell death in chronic myeloid leukemia cells, although autophagy can act as a “double-edged sword” contributing to cell survival or cell death. Here we evaluated the role of autophagy in thioridazine (TR)-induced cell death in the human ALL model. TR induced apoptosis in ALL Jurkat cells and it was not cytotoxic to normal peripheral mononuclear blood cells. TR promoted the activation of caspase-8 and -3, which was associated with increased NOXA/MCL-1 ratio and autophagy triggering. AMPK/PI3K/AKT/mTOR and MAPK/ERK pathways are involved in TR-induced cell death. The inhibition of the autophagic process enhanced the cytotoxicity of TR in Jurkat cells, highlighting autophagy as a targetable process for drug development purposes in ALL.

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