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Published on: September 18, 2013
Improved outcome of acute lymphoblastic leukaemia treated by delayed intensification in Hong Kong children: HKALL97
1Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. ckli@cuhk.edu.hk
Insights
Intensified chemotherapy protocols significantly reduced relapse rates in children with acute lymphoblastic leukaemia. This approach improved event-free survival, demonstrating a more effective treatment strategy for paediatric leukaemia.
Area of Science:
- Paediatric Oncology
- Clinical Haematology
- Leukaemia Research
Background:
- Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer.
- Treatment protocols aim to maximize cure rates while minimizing toxicity.
- Delayed intensification strategies have been explored to improve outcomes in ALL.
Purpose of the Study:
- To evaluate the efficacy of a modified Berlin-Frankfurt-Muenster 95 (BFM95) protocol in children with acute lymphoblastic leukaemia.
- To assess the impact of one or two delayed intensification phases on treatment outcomes.
- To compare the outcomes of the HKALL97 protocol with historical controls (HKALL93 study).
Main Methods:
- Prospective, single-arm, multicentre study conducted in Hong Kong.
- Inclusion of 171 children aged 1-17.9 years with newly diagnosed ALL.
- Modified BFM95 chemotherapy protocol with delayed intensification, including double intensification for high-risk patients.
Main Results:
- Achieved a 95.3% induction remission rate with low non-leukaemia mortality (2.3%).
- Significantly reduced 4-year relapse rates compared to the previous HKALL93 study (15.7% vs 37.3%, P<0.001).
- Improved 4-year event-free survival (79% vs 65%, P=0.007), particularly in the intermediate-risk group.
Conclusions:
- A more intensive delayed consolidation phase effectively reduced relapses in childhood ALL.
- The modified protocol demonstrated improved event-free survival, especially for intermediate-risk patients.
- Early treatment complications were manageable, with sustained low non-leukaemia mortality.
Objective:
To study the outcome of children with acute lymphoblastic leukaemia who were treated using a protocol including one or two delayed intensifications.
Design:
Prospective single-arm multicentre study.
Setting:
Five designated children cancer units of the Hospital Authority of Hong Kong.
Patients:
Children aged between 1 and 17.9 years with newly diagnosed acute lymphoblastic leukaemia seen from November 1997 to December 2002.
Intervention:
Chemotherapy was modified from a German Berlin-Frankfurt-Muenster 95 (BFM95) protocol that included a delayed intensification similar to the induction phase repeated 5 months after diagnosis. High-risk patients were given double delayed intensification.
Main Outcome Measures:
Overall survival and event-free survival of the whole group and the three risk groups (standard-, intermediate-, and high-risk groups), and comparison with historical controls.
Results:
A total of 171 patients were recruited with a median age at diagnosis of 5.57 years (range, 1.15-17.85 years). The induction remission rate was 95.3% and non-leukaemia mortality during remission was 2.3%. At 4 years, the relapse rate of this (HKALL97) study was significantly lower than that of the HKALL93 study (15.7 vs 37.3%; P<0.001). The 4-year overall survival of HKALL97 and HKALL93 studies were 86.5% and 81.8%, respectively (P=0.51). The 4-year event-free survival for HKALL97 and HKALL93 studies were 79% and 65%, respectively (P=0.007). Nonetheless the difference of event-free survival was most remarkable in the intermediate-risk group: 75.6% and 53.1% for HKALL97 and HKALL93 studies, respectively (P=0.06).
Conclusion:
A more intensive delayed consolidation phase improved the outcome for children with acute lymphoblastic leukaemia by reducing relapses at 4 years. The early treatment complications were manageable and non-leukaemia mortality during remission remained low.