Predicting relapse risk in childhood acute lymphoblastic leukaemia

Abstract

SummaryIntensive multi-agent chemotherapy regimens and the introduction of risk-stratified therapy have substantially improved cure rates for children with acute lymphoblastic leukaemia (ALL). Current risk allocation schemas are imperfect, as some children are classified as lower-risk and treated with less intensive therapy relapse, while others deemed higherrisk are probably over-treated. Most cooperative groups previously used morphological clearance of blasts in blood and marrow during the initial phases of chemotherapy as a primary factor for risk group allocation; however, this has largely been replaced by the detection of minimal residual disease (MRD). Other than age and white blood cell count (WBC) at presentation, many clinical variables previously used for risk group allocation are no longer prognostic, as MRD and the presence of sentinel genetic lesions are more reliable at predicting outcome. Currently, a number of sentinel genetic lesions are used by most cooperative groups for risk stratification; however, in the near future patients will probably be risk-stratified using genomic signatures and clustering algorithms, rather than individual genetic alterations. This review will describe the clinical, biological, and response-based features known to predict relapse risk in childhood ALL, including those currently used and those likely to be used in the near future to risk-stratify therapy.

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

“…Risk stratification groups for pediatric patients were defined by the National Cancer Institute criteria [14]. Risk stratification for all age groups, according to cytogenetic abnormalities was based on previous studies as outlined in the current WHO classification and current criteria [1,15].…”

“…The t(5;14) was found in 1 patient. These translocations are considered low or standard risk by current criteria [1,15,24,25].…”

IKZF1 deletion is an independent prognostic marker in childhood B-cell precursor acute lymphoblastic leukemia, and distinguishes patients benefiting from pulses during maintenance therapy: results of the EORTC Children's Leukemia Group study 58951

“…This suggests that there is still a need for the improvement of therapeutic stratification using new prognostic markers. Risk stratification in contemporary protocols is based on clinical and biological predictors of relapse, mostly related to genetic lesions defining oncogenic subtypes 5,6 and early response to treatment. High hyperdiploidy and the chromosomal translocation t(12;21)/ETV6-RUNX1 are usually associated with a favorable outcome whereas t(9;22)/BCR-ABL1, MLL gene rearrangements, low hypodiploidy and intrachromosomal amplification of chromosome 21 (iAMP21) are associated with a high risk of relapse.…”

Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia

“…33,19,34,35 The list of genetic alterations in childhood ALL that are associated with risk of relapse continues to rise. 36 Some of these factors are well established as predictive of outcomes, whereas others remain to be validated.…”