Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia

Abstract

Context:In acute lymphoblastic leukemia (ALL), the most important prognostic factors are age, leukocyte count at presentation, immunophenotype, and cytogenetic abnormalities. The cytogenetic abnormalities are associated with distinct immunologic phenotypes of ALL and characteristic outcomes.Aims:The present study was primarily aimed at analyzing the impact of cytogenetics on postinduction responses and event-free survival (EFS) in pediatric patients with ALL. The secondary objective was to study the overall survival (OS).Subjects and Methods:A total of 240 patients with age <18 years and diagnosed with ALL between January 2011 and June 2016 were retrospectively analyzed. Cytogenetics was evaluated with conventional karyotyping or reverse transcriptase polymerase chain reaction. Based on cytogenetic abnormalities, the patients were grouped into five categories, and the outcomes were analyzed.Results:Of the 240 patients, 125 (52%) patients had evaluable cytogenetics. Of these, 77 (61.6%) patients had normal cytogenetics, 19 (15.2%) had t(9;22) translocation, 10 (8%) had unfavorable cytogenetics which included t(9;11), hypodiploidy, and complex karyotype, 10 (8%) had favorable cytogenetics which included t(12;21), t(1;19), and high hyperdiploidy, 9 (7.2%) had miscellaneous cytogenetics. Seventy-one percent of patients were treated with MCP 841 protocol, while 29% of patients received BFM-ALL 95 protocol. The 3-year EFS and OS of the entire group were 52% and 58%, respectively. On univariate analysis, EFS and OS were significantly lower in t(9;22) compared to normal cytogenetics (P = 0.033 and P = 0.0253, respectively) and were not significant for other subgroups compared to normal cytogenetics. On multivariate analysis, EFS was significantly lower for t(9;22) and unfavorable subgroups.Conclusions:Cytogenetics plays an important role in the molecular characterization of ALL defining the prognostic subgroups. Patients with unfavorable cytogenetics and with t(9;22) have poorer outcomes.

Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia

“…However, two of these reports have not evaluated the karyotyping data with other prognostic factors in relation to outcome [23,24]. The more recent report evaluated the impact of cytogenetics only on pediatric ALL [25]. To the best of our knowledge, this is the first Indian report to correlate cytogenetics with response to chemotherapy and survival in both adult and pediatric patients with ALL.…”

“…Most of the existing data on cytogenetic abnormalities and their significance in ALL is from the UK-MRC and CALGB ALL trials [8,9]. There are at least three reports from India, that describe results of karyotyping from both adult and pediatric patients respectively [23][24][25]. However, two of these reports have not evaluated the karyotyping data with other prognostic factors in relation to outcome [23,24].…”

Molecular Cytogenetic Study in Patients with Acute Lymphoblastic Leukemia (ALL) in Erbil Province

“…A study by Chennamaneni et al (2018) on the cytogenetic effect on treatment outcomes and survival of children with ALL. A total of 240 patients under the age of 18.…”

“…Out of 240 patients, 125 (52%) were cytogenetically evaluable. Of these, 77 patients (61.6%) had normal cytogenetics, 19 patients (15.2%) had undesirable t (9; 22), 10 patients (8%) had unfavorable cytogenetics, including t (9; 11), hypodiploidy and the karyotype was complex, 10 patients (8%) had favorable cytogenetics including t (12; 21), t (1; 19) and hyperdiploidy, 9 patients (7.2%) had different cytogenetics (Chennamaneni et al, 2018). In the above study, more than half of the subjects had a normal karyotype, while in the present study, less than half of the subjects had a normal karyotype, and the results are not consistent.…”

Hallazgos moleculares y citogenéticos en pacientes pediátricos, diagnosticados de leucemia linfoide aguda

“…Durante mucho tiempo su clasificación estuvo basada en las características morfológicas de los linfoblastos, resultado del estudio del medulograma; posteriormente siendo este superado por el inmunofenotipo celular que permitió analizar la expresión de diversas inmunoglobulinas citoplasmáticas y marcadores de la superficie, que dividen a la LLA de acuerdo a su estirpe celular y sus diferentes estados de maduración [4][5][6]. En la actualidad sin embargo se ha vuelto cada vez más importante el componente genético de la enfermedad, debido a que la mayoría de los pacientes presentan algún grado de alteración a este nivel, ya sea esta de carácter numérico o estructural [7][8][9].…”