Long-Term Follow up of Chinese Children with Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Detection

Introduction and objective: Recent studies from resource-rich countries have showed that minimal residual diseases (MRD) were the most important independent prognostic factor for children with acute lymphoblastic leukemia (ALL). However, experience from Chinese children with this disease has not been reported in the English literature. In this study, we reported our experience in small series of children with ALL based on multi-parameter flow cytometric detection of MRD to study the relationship between MRD levels and the long term survivals in Chinese children with ALL.

Methods: Using multi-parameter flow cytometry and at least one patient specific leukemia associated immunophenotype (LAIP) to determine the MRD levels in 71 Chinese children with ALL expressing leukemia associated immunophenotype (LAIP) from January 2002 to December 2003. Bone marrow aspirates were collected on day 15 and the 1^st, 3^rd, 6^th, 12^th, 18^th, 24^th, 30^th month after chemotherapy. Leukemia associated Immunophenotype for each patient was identified according to the patients’ initial immunophenotypes determined by multi-parameter flow cytometry using a panel of more than 30 antibodies.

Results: The one, two and three year disease free survival (DFS) for patients with a MRD level less than 10⁻² on day 15 were (88.3±6.4) %, (84.3±7.2) % and (76.3±8.5) %, respectively, whereas those for patients with MRD levels ≥10⁻² on day 15 were 100%, 0% and 0%, respectively (log rank test, P=0.004). The 5-year DFS for patients with MRD levels <10⁻² and ≥10⁻² on day 15 were (83.8±6.1) % and 0%, respectively (P<0.01). The 5-year DFS were significantly different between patients with MRD levels <10⁻⁴ and those ≥10⁻⁴ on the 6^th or 12^th month. Out of 71 patients, the 5-year DFS for patients with MRD levels <10⁻³ was 100%, however, the 1-year, 3-year and 5-year DFS for patients with MRD levels ≥10⁻³ were (87.3±5.3) %, (71.4±7.3) % and (68.0±7.7) %, respectively (log rank test, P=0.004). And the 1-year, 3-year and 5-year relapse rates for the latter group were 10.5%, 13.5% and 15.8%, which showed a tendency of difference in terms of relapse rate when compared to patients with MRD levels <10⁻³ (5-year relapse rate: 15.8% vs. 0%, P=0.08).

Conclusions: MRD detected by multi-parameter flow cytometry is also an independent prognostic factor in Chinese children with ALL.