scholarly journals Acute leukemia of childhood: A single institution's experience

2005 ◽  
Vol 57 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Bojana Slavkovic ◽  
Marija Guc-Scekic ◽  
Gordana Bunjevacki ◽  
S. Djuricic ◽  
Aleksandra Krstic ◽  
...  

The aim of this study was to investigate distribution of immunophenotypic and cytogenetic features of childhood acute leukemia (AL) in the cohort of 239 newly diagnosed patients registered at the leading pediatric oncohematology center in the country during a six-year period (1996-2002). With approximately 60-70% of all childhood AL cases in Serbia and Montenegro being diagnosed and treated in this institution the used data represent a valid research sample to draw conclusions for entire country. On the basis of five phenotypic markers, the distribution of immunological subtypes was as follows: 169 (70.7%) expressed B-cell marker CD19 (137 were CD10 positive and 32 CD10 negative), 37 (15.5%) belonged to T-lineage acute lymphoblastic leukemia (T-ALL) (cyCD3 positive), and 33 (13.8%) were acute myeloblastic leukemia (AML) (CD13 positive and/or CD33 positive in the absence of lymphoid-associated antigens). The ratio of males and females was 1.5:1. Most of the cases were between the ages of 2 and 4, and were predominantly B-lineage acute lymphoblastic leukemia (B-ALL) cases. Another peak of age distribution was observed at the age of 7. The frequency of T-ALL (18% of ALL) was similar to that reported for Mediterranean countries: France (19.4%), Greece (28.1%), Southern Italy (28.3%), and Bulgaria (28.0%). Cytogenetic analyses were performed in 193 patients: 164 ALL and 29 AML. Normal karyotype was found in 57% of ALL and in 55% of AML patients, while cytogenetic abnormalities including structural, numerical, and complex chromosomal rearrangements were found in 43% of ALL and in 45% of AML patients. Our results represent a contribution to epidemiological aspects of childhood leukemia studies.

2009 ◽  
Vol 12 (1) ◽  
pp. 21-35 ◽  
Author(s):  
O Gra ◽  
Zh Kozhekbaeva ◽  
O Makarova ◽  
E Samochatova ◽  
T Nasedkina

Polymorphism of Biotransformation Genes and Risk of Relapse in Childhood Acute LeukemiaLeukemia is a hematological malignancy that involves bone marrow. Polymorphism of biotransformation genes plays an important role in primary childhood leukemia and affects the incidence and character of acute leukemia relapse. A biochip designed to assess some polymorphisms of biotransformation genes was used to determine the frequency of the polymorphic variants ofCYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19andNAT2in 332 children with acute lymphoblastic leukemia (ALL) and 71 children with acute myeloblastic leukemia (AML). TheCYP1A1 *1/*2A, GSTT1non null andGSTM1non null genotypes were more frequent in patients with primary leukemia than in relapse. Analysis of theNAT2genotype frequency revealed a characteristic genotype for each type of leukemia, which prevailed in patients with relapse: the genotype341C/-, 481T/-, 590G/G, 857G/Gprevailed in ALL patients with relapse, and the genotype341T/T, 481C/C, 590A/- in AML patients with relapse when compared with patients having primary ALL or AML, respectively. Thus, the polymorphisms ofCYP1A1, GSTT1, GSTM1andNAT2genes can be considered as markers for risk of relapse in childhood acute leukemia and can be used for the prognosis and individualization of standard therapy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1729-1729
Author(s):  
Thai Hoa Tran ◽  
Marian H. Harris ◽  
Jonathan V. Nguyen ◽  
Traci M. Blonquist ◽  
Kristen E. Stevenson ◽  
...  

Abstract Background. Recurrent chromosomal rearrangements carry prognostic significance in pediatric B-lineage acute lymphoblastic leukemia (B-ALL). Recent genome-wide analyses identified a diverse spectrum of chromosomal rearrangements resulting in novel chimeric fusions associated with poor prognosis when treated with conventional chemotherapy. These fusions are observed more frequently in NCI High-Risk (HR) B-ALL compared with NCI Standard Risk (SR) patients. They often activate ABL and JAK-STAT signaling pathways and have demonstrated sensitivity to the relevant tyrosine kinase inhibitors (TKIs) in in vitro assays and ex vivomodels. The objective of this study was to determine the frequency of NCI HR B-ALL patients enrolled on DFCI ALL Consortium Protocol 05-001 with a kinase-activating fusion that would be amenable to TKI therapy and to describe their associated clinical characteristics and outcomes. Methods. Between 2005-2011, 219 NCI HR, Philadelphia chromosome (Ph)-negative, B-ALL patients were enrolled on DFCI ALL Consortium Protocol 05-001, 105 of whom had sufficient material to undergo kinase fusion testing by validated multiplex reverse transcription polymerase chain reaction (RT-PCR) assays. A total of 35 kinase fusions of ABL-class (ABL1, ABL2, PDGFRB, CSF1R), JAK2 and CRLF2 rearrangements were examined. IGH@-CRLF2 and EPOR rearrangements were not assessed. Fusion products were predicted by NCBI BLAST algorithms, confirmed by singleplex PCR and Sanger sequencing and aligned using CLC Main Workbench Version 7.6.1. IKZF1 deletion (del) status had previously been assessed by multiplex ligation-dependent probe amplification (MLPA). Fisher's exact test and the Wilcoxon rank sum test were used to compare patient characteristics to those with and without any identified fusion for categorical and continuous variables respectively. Event-free survival (EFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared using a log rank test. Univariate and multivariable Cox proportional hazards models of EFS were constructed. Results. Among 105 NCI HR, Ph-negative, B-ALL patients, 16 (15%) were found to harbor an ABL-class fusion (ETV6-ABL1: n=1; FOXP1-ABL1: n=1; SFPQ-ABL1: n=1; ZC3HAV1-ABL2: n=1) or a fusion activating the JAK-STAT pathway (P2RY8-CRLF2: n=8; PAX5-JAK2: n=4). Sixty-nine percent of patients with an identified fusion (Fusion +) had a concomitant IKZF1 del (n=11). Features associated with fusion-positivity were age of 10 years or older (p=0.003), male sex (p=0.03), Hispanic ethnicity (p=0.01) and IKZF1 del (p=0.0005) (Table 1). Fifty percent of Fusion+ patients experienced an event (induction death (n=1); induction failure (n=1); or relapse (n=6)) compared to 24% of patients without a fusion. The 5-year EFS and OS were 48% (95% CI 22-70%) and 68% (95% CI 39-85%) for Fusion+ patients compared to 78% (95% CI 67-85%) and 88% (95% CI 79-93%) for those without fusions (Figure 1). In univariate analysis, fusion-positivity (HR: 2.66, p=0.02) and IKZF1 del (HR: 3.21; p=0.0018) were each significantly associated with inferior EFS, while age and presenting leukocyte count were not. In multivariable analysis, IKZF1 del, but not fusion-positivity, retained statistical significance (HR: 2.64, p=0.02). Conclusion. Fifteen percent of NCI HR, Ph-negative, B-ALL patients enrolled on DFCI ALL Consortium 05-001 were found to have a kinase-activating fusion. Fusion+ patients frequently harbored concomitant IKZF1 deletion and had an inferior outcome. Future studies should focus on developing clinical strategies to rapidly identify these patients at diagnosis and to test whether the addition of the relevant TKIs to their treatment will improve their outcome. Disclosures Asselin: Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Sigma Tau Pharamceuticals: Consultancy. Loh:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding.


Author(s):  
Erin C. Peckham-Gregory ◽  
Minh Ton ◽  
Karen R. Rabin ◽  
Heather E. Danysh ◽  
Michael E. Scheurer ◽  
...  

Acute leukemia is the most common pediatric malignancy. Some studies suggest early-life exposures to air pollution increase risk of childhood leukemia. Therefore, we explored the association between maternal residential proximity to major roadways and risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Information on cases with acute leukemia (n = 2030) was obtained for the period 1995–2011 from the Texas Cancer Registry. Birth certificate controls were frequency matched (10:1) on birth year (n = 20,300). Three residential proximity measures were assessed: (1) distance to nearest major roadway, (2) residence within 500 meters of a major roadway, and (3) roadway density. Multivariate logistic regression was used to generate adjusted odds ratios (aOR) and 95% confidence intervals (CI). Mothers who lived ≤500 meters to a major roadway were not more likely to have a child who developed ALL (OR = 1.03; 95% CI: 0.91–1.16) or AML (OR = 0.84; 95% CI: 0.64–1.11). Mothers who lived in areas characterized by high roadway density were not more likely to have children who developed ALL (OR = 1.06, 95% CI: 0.93–1.20) or AML (OR = 0.83, 95% CI: 0.61–1.13). Our results do not support the hypothesis that maternal proximity to major roadways is strongly associated with childhood acute leukemia. Future assessments evaluating the role of early-life exposure to environmental factors on acute leukemia risk should explore novel methods for directly measuring exposures during relevant periods of development.


Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 150-156 ◽  
Author(s):  
Y Hayashi ◽  
CH Pui ◽  
FG Behm ◽  
AH Fuchs ◽  
SC Raimondi ◽  
...  

The frequency and characteristics of childhood acute leukemia with a 14q32 translocation [other than the t(8;14)(q24;q32)] were determined in 335 cases of newly diagnosed acute lymphoblastic leukemia (ALL) and 105 cases of acute nonlymphoblastic leukemia (ANLL). Ten children, representing 2.3% of the entire cohort, had this abnormality (1.5% of ALL patients and 4.8% of ANLL patients). By French-American-British (FAB) criteria, 4 cases were classified as L1, 1 as L2, 2 as M1, 1 as M2, and 2 as M5. Remarkably, mixed-lineage expression was found in 6 of these 10 cases, but in only 21 of the other 430 cases without a 14q32 translocation (P less than .001). Leukemic cells from 5 of these 6 cases (4 ANLL, and 1 ALL) coexpressed CD13, a myeloid-associated antigen, and CD2, a T-cell-associated antigen; blasts from the sixth case (ALL) coexpressed CD13 and CD19, a B-lineage-associated antigen. Thus, in addition to the well-described 11q23 translocations and t(9;22), 14q32 translocations also appear to be associated with mixed lineage antigen expression. Break-points of the reciprocal chromosomes from chromosome 14 were identified in five of these cases: 1q23, 6q23- q25, 7p15, 8q11, and 12q13. Of the four mixed-lineage cases that were tested, none showed rearrangement of the immunoglobulin heavy chain (IgH) gene. This suggests that the 14q32 breakpoint does not involve the IgH gene and that an unidentified important gene may reside on 14q32.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 857-857 ◽  
Author(s):  
Melanie Fakler ◽  
Sandra Löder ◽  
Meike Vogler ◽  
Katja Schneider ◽  
Irmela Jeremias ◽  
...  

Abstract Children with high risk acute lymphoblastic leukemia (ALL) do not respond well to current treatments. This failure is, at least in part, due to defects in apoptosis programs. Therefore, new strategies are required that counter apoptosis resistance in order to improve the poor prognosis of high risk pediatric acute leukemia. Since XIAP, a member of “Inhibitor of Apoptosis Proteins” (IAPs), is expressed at high levels in acute leukemia and blocks apoptosis at a central point of the apoptotic machinery, XIAP may present a suitable molecular target for therapeutic intervention. Here, we report that neutralizing XIAP by small molecule inhibitors is a novel and effective approach to sensitize childhood acute leukemia cells for TRAIL- or chemotherapy-induced apoptosis. XIAP inhibitors at subtoxic concentrations, but not a structurally related control compound, synergize with TRAIL to induce apoptosis in acute lymphoblastic leukemia cells. Also, XIAP inhibitors act in concert with TRAIL to reduce clonogenic growth of ALL cells demonstrating that they suppress long-term survival. Analysis of signaling pathways reveals that XIAP inhibitors enhance TRAIL-induced activation of caspases, loss of mitochondrial membrane potential and cytochrome c release in a caspase-dependent manner, indicating that they promote a caspase-dependent feedback mitochondrial amplification loop. Intriguingly, XIAP inhibitors overcome Bcl-2-mediated resistance to TRAIL by enhancing Bcl-2 cleavage and Bak conformational change. Thus, XIAP inhibitors combined with TRAIL even break Bcl-2-imposed resistance, a defect in the apoptotic pathway that is common in acute leukemia and associated with poor prognosis. Further, XIAP inhibitors prime ALL cells for apoptosis induced by various anti-leukemic drugs, e.g. cytarabine, doxorubicin, etoposide and 6-mercaptopurine, or by agonistic anti-CD95 antibody. Notably, XIAP inhibitors kill leukemic blasts from children with ALL ex vivo and cooperate with TRAIL to induce apoptosis. In contrast to malignant cells, XIAP inhibitors at equimolar concentrations alone or in combination with TRAIL are non-toxic to normal peripheral blood mononuclear cells despite expression of the apoptosis-inducing TRAIL receptors on the cell surface, pointing to a therapeutic window. Most importantly, XIAP inhibitors significantly reduce leukemic burden in vivo in a mouse model of pediatric ALL engrafted in NOD/SCID mice. Thus, small molecule XIAP inhibitors present a promising novel approach for apoptosis-based therapy of childhood acute leukemia.


Blood ◽  
1990 ◽  
Vol 76 (1) ◽  
pp. 150-156 ◽  
Author(s):  
Y Hayashi ◽  
CH Pui ◽  
FG Behm ◽  
AH Fuchs ◽  
SC Raimondi ◽  
...  

Abstract The frequency and characteristics of childhood acute leukemia with a 14q32 translocation [other than the t(8;14)(q24;q32)] were determined in 335 cases of newly diagnosed acute lymphoblastic leukemia (ALL) and 105 cases of acute nonlymphoblastic leukemia (ANLL). Ten children, representing 2.3% of the entire cohort, had this abnormality (1.5% of ALL patients and 4.8% of ANLL patients). By French-American-British (FAB) criteria, 4 cases were classified as L1, 1 as L2, 2 as M1, 1 as M2, and 2 as M5. Remarkably, mixed-lineage expression was found in 6 of these 10 cases, but in only 21 of the other 430 cases without a 14q32 translocation (P less than .001). Leukemic cells from 5 of these 6 cases (4 ANLL, and 1 ALL) coexpressed CD13, a myeloid-associated antigen, and CD2, a T-cell-associated antigen; blasts from the sixth case (ALL) coexpressed CD13 and CD19, a B-lineage-associated antigen. Thus, in addition to the well-described 11q23 translocations and t(9;22), 14q32 translocations also appear to be associated with mixed lineage antigen expression. Break-points of the reciprocal chromosomes from chromosome 14 were identified in five of these cases: 1q23, 6q23- q25, 7p15, 8q11, and 12q13. Of the four mixed-lineage cases that were tested, none showed rearrangement of the immunoglobulin heavy chain (IgH) gene. This suggests that the 14q32 breakpoint does not involve the IgH gene and that an unidentified important gene may reside on 14q32.


2018 ◽  
Vol 5 (6) ◽  
pp. 2123
Author(s):  
Adewumi B. Oyesakin ◽  
Vincent E. Nwatah ◽  
Nwankwo U. Ukpai ◽  
Ekaette I. David ◽  
Tamunomieibi T. Wakama ◽  
...  

Background: Acute leukemia is the most common childhood malignancy but its occurrence in low- and middle-income countries are under-reported. Its pattern of presentation varies depending on several factors. The objective of this report is to determine the pattern of presentation of acute leukemias in children at a tertiary hospital in Nigeria.Methods: A retrospective cross-sectional study of children managed for acute leukemia at the Paediatric Department in a 5-year period. Of 31 patients, 27 had adequate records, which were reviewed. Data collected include patient’s demographics, clinical features and treatment outcome.Results: There were 16 males and 11 females, aged 8 months to 16 years (mean 7.45 years ±4.75 SD). The pattern of clinical features were fever (85.2%), pallor (92.6%) and splenomegaly (51.9%). The specific leukemia type ratio for Acute Myeloid leukemia (AML) and Acute lymphoblastic leukemia (ALL) was 1: 2.9. The parents of three patients took their children away before commencement of treatment, one patient completed treatment and 6 (22.2%) died before completing treatment. Nearly half of the patients were lost to follow up to seek alternative care while 9 (33.3%) of the patients were in remission at last follow up. Lost to follow-up was found not to be significantly associated with socioeconomic status, age and sex respectively.Conclusions: Acute lymphoblastic leukemia remains the predominant type of childhood leukemia in our setting. Majority of the patients presented with fever and pallor moreover the default to follow-up plagues treatment completion.


2014 ◽  
Vol 6 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Deepak Khadka ◽  
Ananda Sharma ◽  
Jeevan K Shrestha ◽  
Gauri S Shrestha ◽  
Pun N Shrestha ◽  
...  

Introduction: In some instances, the understanding of the ocular manifestations in childhood leukemia is not only important to establish the diagnosis but also reflects the disease state and prognosis. Objective: To study the ocular manifestations of childhood acute leukemia among the children attending a tertiary-level hospital in Nepal. Materials and methods: A cross-sectional, descriptive study was undertaken at the B.P. Koirala Lions Centre for Ophthalmic Studies (BPKLCOS) and Kanti Children Hospital (KCH), Kathmandu, over a period of one-and-a-half years. Children diagnosed with acute childhood leukemia referred to the BPKLCOS from the Oncology Unit of the KCH and the Emergency Department of the Tribhuvan University Teaching Hospital (TUTH) were included in the study, using a non-probability sampling method. Results:Of the 71 cases with childhood acute leukemia, 55 (77.5%; 95% CI = 66% - 85%) had acute lymphoblastic leukemia(ALL)whereas the other 16 (23%) had acute myeloblastic leukemia (AML). Ocular involvement were seen in 33 cases (46%) and were more frequent in cases of AML as compared to those with ALL (p=0.001, OR 5.0, 95% CI= 1.4 – 17.5). Direct ocular involvement and secondary ocular involvement were observed in 12 (16.9%) and 29 (40.8%) subjects, respectively. Ocular symptoms were present in only 11 cases (15.49%). Cerebro-spinal fluid (CSF) and bone marrow examination in cases with direct ocular involvement showed 10 cases (83.3%) positive for blast cells in the CSF and 6 cases (50%) positive for blast cells in bone marrow. The most common secondary manifestation was retinal haemorrhage, seen in 23 cases (32.4%). Conclusion: In view of the high asymptomatic ocular involvement and the significant visual morbidity, a routine ophthalmic examination is recommended as an integral part of the medical examination in all cases of childhood acute leukemia.DOI: http://dx.doi.org/10.3126/nepjoph.v6i2.11678Nepal J Ophthalmol 2014; 6(12):  pp. 197-204


1970 ◽  
Vol 4 (1) ◽  
pp. 102-107 ◽  
Author(s):  
D Khadka ◽  
AK Sharma ◽  
JK Shrestha ◽  
B Pant ◽  
S Pant ◽  
...  

Introduction: Sub-hyaloid haemorrhage is common in acute leukemia. Objective: To investigate the effects of Nd: YAG Laser hyaloidotomy in 11 eyes of 8 patients with pre-macular haemorrhage in acute childhood leukemia. Materials and methods: Premacular sub-hyaloid haemorrhage is one of the leading causes of visual disability in children with acute leukemia. Eleven eyes of 8 patients attending Kanti Children Hospital and BP Koirala Lions Centre for Ophthalmic Studies from January 2006 to July 2007 with premacular subhyaloid haemorrhage were included in the study and treated with Nd: YAG Laser. The haemorrhage originated from acute myeloid leukemia (AML) in 4 cases (6 eyes) and acute lymphoblastic leukemia (ALL) in 4 cases (5 eyes). Results: Drainage of premacular sub-hyaloid haemorrhage into the vitreous cavity within 3 months succeeded in 9 eyes out of 11 eyes treated. One eye had a dense clotted haemorrhage and the other had a re-bleed. Overall visual improvement was equal in both AML and ALL cases. No obvious epiretinal membrane, retinal breaks and tractional retinal detachment occurred in any eye. Conclusion: Nd: Yag laser hyaloidotomy is a relatively safe, simple and alternative treatment for eyes with a dense premacular sub-hyaloid haemorrhage in acute childhood leukemia. The risks and benefits have to be weighed in randomized clinical trials to establish Nd: YAG hyaloidotomy treatment as a routine procedure in leukemic children. DOI: http://dx.doi.org/10.3126/nepjoph.v4i1.5860 NEPJOPH 2012; 4(1): 102-107


2015 ◽  
Vol 37 (1) ◽  
pp. 64-69 ◽  
Author(s):  
A Lahjouji ◽  
F Bachir ◽  
S Bennani ◽  
A Quessar ◽  
S Amzazi

Background: There is paucity of detailed studies of adult T cell acute lymphoblastic leukemia (T-ALL) in developing countries reflecting the condition of these patients including clinical and biological features. Objective: This study was carried out to analyze the immunophenotypic characteristics of 40 Moroccan patients with T-ALL and its association with biological and clinical features. Patients and Methods: Between 2006 and 2009, 130 adult patients diagnosed with acute lymphoblastic leukemia (ALL) were immunophenotyped by 3-color flow cytometry using a panel of monoclonal antibodies. Cases presenting features of a T-lineage phenotype were subjected to detailed analysis including immunophenotypic, clinical and biological parameters. Results: Proportion of T-ALL among ALL Moroccan patients was 31.0%. Median age of patients was 28 years. Twenty-nine patients were females and 11 were males. 45.0% of patients (18/40) had features of immature T-ALL stages (pro-T and pre-T ALL), 30.0% (12/40) of CD1a+ cortical T-ALL stage and 25.0% (10/40) had a characteristic phenotype of medullary T-ALL. The frequencies of progenitor cell markers CD10, CD34 and TdT expression were 14.0; 57.5% and 50.0% respectively. The aberrant expression of B lineage associated antigen CD79a were positive in 20.5% of the cases and the aberrant expression of myeloid antigens CD13 and/ or CD33 was found in 22 (55.0%) cases. No significant association was encountered between TdT, CD34 or myeloid antigens positivity and high risk features at presentation as age, sex, and white blood cells. However, myeloid antigens (CD13 and/or CD33) was significantly associated with T-cell maturation stages (p = 0.009). Conclusion: To the best of our knowledge, this is the first report from North Africa of immunophenotypic study on adult T-ALL. Our findings indicate that the proportion of T-ALL among ALL in Morocco is similar to that reported in others Mediterranean countries like France and Italy and that myeloid-associated antigens expression is frequently associated with immature immunophenotype.


Sign in / Sign up

Export Citation Format

Share Document