medwireNews: Adult patients with acute lymphoblastic leukemia (ALL) are more likely to require high-risk chemotherapy than their pediatric counterparts, demonstrate results from a study using standardized diagnostic, risk assessment and treatment protocols.
Data for the 749 patients treated using the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol showed that patients aged 18 to 45 years were more likely to have T-lineage ALL than patients aged 1 to 9 or 10 to 17 years (34 vs 11 and 27%, respectively). The proportion of T-lineage ALL patients with a white blood cell count above 100 x 109/L also fell significantly with increasing age.
In addition, the oldest patients had a poorer minimal residual disease response on Day 29 of treatment than the two younger age groups (51% achieving <0.1% vs 74 and 62%, respectively) and were more likely to have an MLL-AF4 gene translocation (10% vs 3% and 3%, respectively).
This resulted in 24% of adult patients being stratified to receive high-risk chemotherapy at day 29, compared with just 10% of patients aged 1 to 9 years and 18% of patients aged 10 to 17 years, report Kjeld Schmiegelow (University of Copenhagen, Denmark) and co-investigators in the European Journal of Haematology.
Other cytogenetic aberrations also showed skewed distribution, with children in the youngest age group having more t(12;21) translocations and hyperdiploidy than older patients, while children aged 10 to 17 years were most likely to have RUNX1 amplification.
The authors explain that the NOPHO ALL-2008 protocol for patients with Philadelphia chromosome-negative B cell precursor or T-lineage ALL was designed to determine whether the significant discrepancy in ALL survival between children and adults can be explained by differences in induction or consolidation treatment approaches or adherence.
"As adults have a higher frequency of T-ALL and [high risk] cytogenetics and show less favorable response to induction treatment, the critical clinical question is really whether adults and children who are diagnosed and stratified according to identical criteria have different prognoses within each risk group," they comment.
"This question will be addressed in the ongoing prospective evaluation of the Nordic/Baltic NOPHO ALL-2008 treatment protocol."
The researchers add that the identical length of induction and consolidation therapy in adults and children treated with the NOPHO ALL-2008 protocol does not bear out the hypotheses that the relatively low adult ALL survival is due to nonadherence to treatment or an inability to tolerate the intensive regimens used in younger patients.
"These findings indicate that the biology of the disease changes with increasing age, and this may contribute to the poor treatment response seen in adult ALL patients," Schmiegelow et conclude.
"Further studies are needed to reveal whether a response-directed approach can improve the poorer long-term survival of adult patients."
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