ABSTRACT
Objective: To analyse the frequencies of clinical and laboratory risk factors and cytogenetic abnormalities in Jordanian children with acute lymphoblastic leukaemia and their response to therapy.
Methods: We conducted a retrospective analysis of 116 paediatric acute lymphoblastic leukaemia cases diagnosed and treated in Queen Rania Hospital for Children between January 2015 and December 2019. Children were diagnosed by bone marrow aspirate microscopic examination and flow cytometry. Cytogenetic anomalies were detected using fluorescence in situ hybridisation. Descriptive analysis was given for the age, gender, acute lymphoblastic leukaemia immune phenotype, cytogenetic anomalies, initial white cell count, and initial response to chemotherapy. These variables were correlated in frequencies with each other and with response to treatment in order to detect high risk groups and characteristic patterns.
Results: The ages ranged from 3 months to 14 years with a peak age group of 1-4 years and almost equal gender distribution. B-cell acute lymphoblastic leukaemia was diagnosed in 104 (89.7%) cases, while 12 (10.3%) were of T-cell lineage. CD10 negativity was detected in 10 cases (9.6%), high white cell count in 18 (15.5%), t(12;21) in 15 (14.4%), t(9;22) in 4 (3.8%) and 11q23 rearrangement in 3 infants (2.9%). A poorer response to therapy and higher mortality was detected in T-cell subtype, infancy, older age, high white cell count, presence of t(9;22) and 11q23 rearrangement, and slow responders to initial chemotherapy.
Conclusion: Identifying adverse prognostic factors of the most common paediatric leukaemia allows for tailoring chemotherapy protocols, closer monitoring of high risk groups to improve treatment outcomes.
Key words: Acute lymphoblastic leukaemia, ALL, cytogenetics, t(9;22), 11q23.
RMS August 2023; 30 (2): 10.12816/0061604
Introduction
Acute lymphoblastic leukaemia (ALL)
is a clonal neoplasm of the blood and bone marrow (BM) arising from an
uninhibited proliferation of lymphoblasts, which are the immature precursor
cells of B or T lymphocytes (1).
It is the most common childhood leukaemia and accounts
for 25% of all malignancies in children (2,3). The incidence is estimated at
3.4 per 100,000 people in the United States and the majority of cases are of
the B-ALL type (4,5). Long-term survival increased over the past decade to
exceed 80% in developed countries. Although lower rates are observed in developing
countries, prognosis is improving with recent advances and better access to
health care (6-9).
Certain clinical, immunophenotypic and cytogenetic
features influence the response of ALL to treatment, and their evaluation aids
the risk stratification of patients. High risk features include
age <1 year or ≥10 years, male gender, CNS involvement, initial white blood
count ≥50× 10⁹/ L for B-ALL and ≥100× 10⁹/L for T-ALL, T-cell lineage, BCR–ABL
positive, and MLL rearrangements among others (10,11).
This study analysed the above-mentioned features in
children diagnosed with and treated for ALL at Queen Rania Hospital for
Children (QRH) in correlation with their response to chemotherapy in order to
identify higher-risk ALL patients and administer the proper chemotherapy
protocols.
Methods
Prior approval of the ethics committee
was acquired at the Royal Medical Services in March 2021.
This retrospective
study included 116 patients under 14 years of age who were diagnosed with ALL between
January 2015 and December 2019. Over this period, the average follow up time
for patients was 3 years.
Children from different geographical areas in Jordan
were referred to QRH for further evaluation, diagnosis, treatment and follow
up. A diagnosis of ALL was made when 20% or more lymphoblasts were observed
upon microscopic examination of BM smears and confirmed by immunophenotyping
using the Becton Dickinson fluorescence activated cell sorter Canto II, See figure
1. BM specimens were also tested by fluorescence in situ hybridisation for three specific anomalies: t(12;21), also
known as the ETV6-RUNX1 rearrangement, t(9;22) which is known as the
Philadelphia chromosome or BCR-ABL1 fusion gene, and the MLL gene
rearrangements (11q23).
All of our study patients received chemotherapy at QRH
and their remission statuses were assessed at the following points: after
induction chemotherapy, after completing consolidation treatment, and at any
point where there is clinical or laboratory suspicion of disease relapses.
Remission is defined as the morphologic evidence of less than 5% blasts in the
BM (12).
Electronic medical records were retrospectively
reviewed to collect the following data: age, gender, immunophenotypic subtype,
and WBC at the time of diagnosis, Cytogenetic study results were collected form
the department’s records. Data were analysed using Microsoft Excel Spreadsheet
Software 2010 and descriptive analysis using frequencies was applied to the
variables of this study.
Exclusion
criteria were age above 14 years, patients who were not diagnosed or did not
receive their treatment in QRH, acute leukaemia of myeloid lineage,
lymphoblastic lymphomas without BM involvement, as well as high risk syndromes
including Down syndrome, Fanconi anaemia,