Departments of Anatomical & Cellular Pathology and ^*Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong

Childhood acute lymphoblastic leukaemia (ALL) is a heterogeneous blood malignancy with diverse clinical outcomes. The stratification of children to risk-directed therapy has contributed to substantial improvements in treatment. We applied nested reverse-transcription polymerase chain reaction (RT-PCR), cytogenetic analysis and flow cytometry to diagnostic bone marrow (BM) of 68 consecutive de novo childhood ALL at Prince of Wales Hospital from September 1995 to July 2000. We also monitored minimal residual disease (MRD) in the cohort of children with TEL/AML1 rearrangement. TEL/AML1 was detected in 18% (11/61) children with B-lineage ALL, of the median age of 6 years (range, 2 - 14) and white cell count of 7.0 x 10⁹/L (2.4 - 88.2 x 10⁹), but in none of 7 childhood T-lineage ALL. In addition, TEL/AML1 did not co-exist with E2a/PBX1, MLL/AF4 and BCR/abl fusion genes from t(1;19), t(4;11) and t(9;22) respectively. Immunophenotyping showed that TEL/AML1 was restricted to CD10+ B-precursor cell ALL and was associated with aberrant expressions of cross-lineage cellular antigens (p = 0.015). Karyotyping demonstrated no discernible t(12;21)(p13;q22), nevertheless 36.4% (5/11) of TEL/AML1+ children showed either numeric or structural abnormalities. The modal number of 5 TEL/AML1+ children with abnormal cytogenetics ranged from 43 to 48. Hyperdiploidy was found in 18.2% (2/11) children. The non-random t(12;21)(p13;q22) evident by TEL/AML1 was associated with trisomy 21, non-specific deletion of 6q and the loss of the normal TEL allele displaying the subtle 12p- in 9.1% (1/11), 18.2% (2/11) and 9.1% (1/11) children respectively. At 4 weeks post-induction therapy rapid clearance of TEL/AML1 was noted in 54.5% (6/11) children. MRD was found in 28.6% (2/7) children with BM available at 6 months post-consolidation therapy. Upon the completion of the maintenance therapy at 24 months, MRD was detected in 14.3% (1/7) children. None of the children with a negative MRD post-induction therapy had TEL/AML1 detected later during the consolidation and maintenance therapy. To-date 18.2% (2/11) children relapsed at 47 and 50 months from diagnosis. The children showed no MRD until relapse. The overall event-free survival of 11 TEL/AML1+ children at the median of 48 months was 80%. Our data suggest that the rapid clearance of the fusion gene and the long duration of clinical remission in most the children may reflect the high sensitivity of TEL/AML1+ leukaemic clones to chemotherapy.