New prognostic markers help identify risk of relapse

A recently completed clinical study has found new prognostic markers that may help clinicians identify those children with leukaemia who are at high risk of relapse and are most in need of intensified treatment to improve their chance of survival.

The retrospective clinical study, performed jointly by the Centre for Children's Cancer and Blood Disorders (CCC&BD)at Sydney Children's Hospital and Children's Cancer Institute Australia, was recently published in the international Journal of Clinical Oncology. Researchers investigated how both normal and malignant blood cells of children with Acute Lymphoblastic Leukaemia (ALL) responded to the first phase of chemotherapy treatment (induction).

Dr Stephen Laughton and co-investigators found that a slow rate of recovery of normal white blood cells at the end of induction, as shown by a low absolute neutrophil count (ANC), was highly predictive of relapse.

"Many traditional predictive factors have lost their significance over time, so there is a real need to find new markers that can be used to identify high-risk patients," said A/Prof Glenn Marshall, Director of the CCC&BD and Head of the Molecular Carcinogenesis Program at CCIA.

"Our work is the first to highlight the fact that the differences in the responses of normal and malignant blood cells may vary between individuals, and, moreover, that this information might be used to adjust therapy on an individual basis."

The study also found, as investigators expected, that high levels of leukaemic cells surviving initial treatment, minimal residual disease (MRD), indicated a high risk of relapse. A technique to determine levels of MRD was pioneered at CCIA.

However, the two prognostic factors (low ANC and high MRD) were found to predict outcome by distinct mechanisms and to have independent prognostic significance.

"These results are very promising," says A/Prof Marshall. "If ANC levels can complement MRD levels at the end of induction in predicting relapse as our study indicates, it may help clinicians identify patients in need of more intensive therapy. At the same time it may be useful in identifying those children who could have reduced therapy and avoid drug side-effects."

The study's authors recommend a prospective clinical trial now be undertaken to test the value of these findings for clinical practice.

Acute lymphoblastic leukaemia (ALL), the most common cancer in children, accounts for about 30% of all deaths from childhood cancer in Australia. While almost all children treated for ALL respond well initially, 20% will develop drug resistance and will relapse with reduced chance of recovery.

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