Risk factors for relapse in childhood acute lymphoblastic leukemia: prediction and prevention

Abstract

With current treatment regimens, survival rates for acute lymphoblastic leukemia (ALL) have improved dramatically since the 1980s, with current 5-year overall survival rates estimated at greater than 85%. This success was achieved, in part, through the implementation of risk-stratified therapy. Nevertheless, for a subgroup of patients (15–20%) with newly diagnosed ALL who will ultimately relapse, traditional risk assessment remains inadequate. The risk of relapse may be estimated on the basis of diagnostic features or early treatment response findings. Further progress in this field may thus come from refinement of predictive factors for relapse and treatment adaptation and from the identification of biological subsets of ALL patients who could benefit from specific target therapies. This article summarizes the aspects associated with the identification of predictive factors for relapse in childhood ALL and options available for prevention of disease recurrence.

Keywords:

• acute lymphoblastic leukemia
• early treatment response
• gene expression profiling
• minimal residual disease
• pediatric
• prognostic factor
• risk factors for relapse

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• For the subgroup of patients (15–20%) with newly diagnosed acute lymphoblastic leukemia (ALL) who will ultimately relapse, traditional risk assessment remains inadequate.

• Prognosis of ALL relapses depends on immunophenotype, time elapsed from the diagnosis of ALL, the sites involved at relapse and intensity of the previous frontline therapy.

• The persistence of minimal residual disease following therapy for ALL has been shown to be the most important prognostic marker in the context of different chemotherapy regimens.

• An increasingly sophisticated understanding of genetic abnormalities in leukemia cells (such as deletions or sequence mutations of genes IKZF1, CRLF2, ERG, and Philadelphia-like ALL), response to treatment and host pharmacogenomics offers the potential to enhance or supplant currently applied prognostic criteria for use in treatment planning for BCP-ALL.

• Risk factors for relapse are treatment dependent, and thus their role may change markedly in different study protocols, or world areas with different socio-economical and health assistance status.

• Adherence with therapy may have a major impact on outcome in childhood BCP-ALL, particularly in adolescents.