ABSTRACT
Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy with the majority of patients being classified as B-cell lineage (B-ALL). The sub-classification of B-ALL is based on genomic architecture. Recent studies have demonstrated the capability of SNP-microarrays to detect genomic changes in B-ALL which cannot be observed by conventional cytogenetic methods. In current clinical trials, B-ALL patients at high risk of relapse are mainly identified by adverse cancer genomics and/or poor response to early therapy. To test the hypothesis that inclusion of SNP-microarrays in frontline diagnostics could more efficiently and accurately identify adverse genomic factors than conventional techniques, we evaluated the Australian high-risk B-ALL cohort enrolled on AIEOP-BFM ALL 2009 study (nâ¯=â¯33). SNP-microarray analysis identified additional aberrations in 97% of patients (32/33) compared to conventional techniques. This changed the genomic risk category of 24% (8/33) of patients. Additionally, 27% (9/33) of patients exhibited a 'hyperdiploid' genome, which is generally associated with a good genomic risk and favourable outcomes. An enrichment of IKZF1 deletions was observed with one third of the cohort affected. Our findings suggest the current classification system could be improved and highlights the need to use more sensitive techniques such as SNP-microarray for cytogenomic risk stratification in B-ALL.
Subject(s)
Ikaros Transcription Factor/genetics , Oligonucleotide Array Sequence Analysis , Polymorphism, Single Nucleotide , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Australia , Child , Child, Preschool , Chromosome Aberrations , Chromosome Banding , Core Binding Factor Alpha 2 Subunit/genetics , Female , Fusion Proteins, bcr-abl/genetics , Gene Deletion , Gene Rearrangement, B-Lymphocyte, Heavy Chain , Humans , In Situ Hybridization, Fluorescence , Infant , Infant, Newborn , Loss of Heterozygosity , Male , Neoplasm, Residual , Oncogene Proteins, Fusion/genetics , Polyploidy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/classification , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prospective Studies , Risk Assessment , Sequence DeletionABSTRACT
Delays or interruptions in chemotherapy due to toxicity such as neutropenia or severe infections are common in the treatment of pediatric acute lymphoblastic leukemia (ALL). Based on the reports of worse outcomes in children with poorer compliance with therapy, there has been concern that toxicity-induced therapy interruptions could also compromise treatment outcome. In a retrospective study of treatment delays in our hospital between 2003 and 2013, the case notes of 141 patients were reviewed. The cumulative lengths of delays during the whole length of chemotherapy, during the intensive phase of treatment, and during maintenance treatment were analyzed. Within these categories, delays were split between less and more than the median value. The risk of relapse did not differ between patients with a longer or shorter delay during the total length of treatment or during the intensive phase. In addition, there was a trend when comparing patients above vs below the mean in length of treatment delays during maintenance, and there was a statistically significant difference in relapses when comparing patients in the lowest and highest quartiles of maintenance delays, with fewer relapses among those patients in the highest quartile for treatment delays.
Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Child , Child, Preschool , Female , Humans , Male , Recurrence , Retrospective Studies , Risk Factors , Time FactorsABSTRACT
AIM: The study aims to analyse clinical data and outcome in Aboriginal and non-Aboriginal children with cancer. METHODS: This is a retrospective case-note review of biological features, treatment outcome and survival in Aboriginal and non-Aboriginal children with a malignancy who were treated at the Women's and Children's Hospital, a tertiary referral hospital, from January 1997 through March 2011. Two separate analyses were performed: firstly, for each Aboriginal patient comparisons were made with two age, sex and diagnosis-matched control patients; then secondly, results for the Aboriginal group of patients were compared with the whole non-Aboriginal group of patients. RESULTS: In the first analysis, Aboriginal children had a significantly higher 'remoteness index' (6.14 vs. 0.95; P < 0.001) and were less likely to be enrolled on clinical trials. Survival analysis of the Aboriginal patients and their matched controls showed a trend towards inferior overall survival for the Indigenous children (P = 0.066). In the second analysis, Aboriginal children tended to have a higher proportion of leukaemias and lymphomas and had an overrepresentation of acute myeloid leukaemia (AML) (P = 0.009). The mean age among Aboriginal children with AML and lymphoma was lower (AML: 3.5 vs. 8 years, P = 0.065; lymphoma: 7.5 vs. 11.9 years, P = 0.01). A higher proportion of Aboriginal children died (P = 0.004). CONCLUSIONS: Aboriginal children present with a somewhat different pattern of cancer, are less likely to be enrolled on studies and seem to have increased mortality. There is a need for improvement in study enrolment, treatment delivery, care coordination and suitably supported residential facilities.
