Improved outcome of acute lymphoblastic leukaemia treated by delayed intensification in Hong Kong children: HKALL97 study

CK Li, KW Chik, SY Ha, ACW Lee, HL Yuen, SC Ling, V Lee, GCF Chan, MMK Shing, LC Chan, MHL Ng
Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong

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.

Hong Kong Med J 2006;12:33-9

Key words: Immunophenotyping; Leukemia, lymphocytic, acute; Methotrexate; Prognosis; Treatment outcome