11 November 2005

Milestone in the Treatment of Childhood Acute Leukemia in Hong Kong
New Strategy Proved Effective in Monitoring Therapy and Risk of Relapse

Leukemias are the most common childhood malignant diseases in Hong Kong, accounting for 30% of pediatric cancers. Despite the high cure rate, childhood acute lymphoblastic leukemia (ALL) is still a major cause of cancer-related deaths in children. 25% of childhood ALL patients may fail therapy, develop relapse and some may eventually die of the disease due to the persistence of low numbers of residual leukemic cells, which are undetectable by conventional method using cytomorphology. On the other hand, some good treatment responders are likely to be over-treated and probably can be cured using less intensive regimens with fewer toxicities and long-term side effects.

It has been demonstrated that information regarding leukemic cell clearance from patient’s bone marrow with induction chemotherapy is a reflection of the interactive outcomes of leukemia and host factors; and it will predict the risk of relapse. Therefore, highly sensitive and specific detection and quantification of these minimal residual leukemic cells during the early months of therapy can provide precise information about the efficacy of chemotherapy. Consolidation therapy and follow-up treatments can thus be tailor-made for individual patients with different types of drugs, and their dosages based on the responses, not only to increase the survival but also improve the long-term quality of life.

With the support from Children’s Cancer Foundation, the Departments of Anatomical and Cellular Pathology and Paediatrics studied 45 ALL children recruited from 5 major hospitals in Hong Kong since September 2003 and traced their minimal residual leukemic cells. To precisely map the cell antigen patterns uniquely expressed by leukemic cells, multiple strategic combinations of antibodies were applied and analyzed using multiparametric flow cytometry. Thirty-five out of the 45 (78%) patients could be successfully traced at Day15, Day33 and Week12 post-induction therapy. And residual leukemic cells could be detected and quantified by this new strategy in 77% at Day 15, 41% at Day 33 and 27% at Week12 among these patients, as compared to 17%, 0% and 0% at the corresponding times by the conventional method.

Researchers are encouraged by the success of this strategy as it provides a closer and more effective monitor on the effect of the therapy and the patients’ risk of relapse. This implies that the clinical relevance of different levels of residual disease could be defined and the ultimate goal of developing the best optimized risk adapted personal therapy with improved survivals and quality of life from reduced toxicities could be achieved in the near future. An extended prospective study is currently underway.