Clinical Investigation of Stratified Therapy in Childhood Acute Promyelocytic Leukemia

OBJECTIVE: The aim of this study was to investigate the clinical biological features, treatment strategy, prognosis and long-term survival in children with acute promyelocytic leukemia（APL）. Focus on the effect of stratified therapy in childhood APL.

METHODS: The clinical data of 42 cases of APL with t (15;17) from April 2004 to December 2012 were analyzed retrospectively. Patients were stratified into three risk-group based on white blood cell count and platelet count at diagnosis: standard, intermediate and high-risk group. Induction treatment consisted of all-trans retinoic acid（ATRA）and Idarubicin（IDA）), followed by multi-drug chemotherapy consolidation and a long term maintenance therapy including ATRA,6-Mercaptopurine（6-MP), Methotrexate（MTX）. The complete remission (CR) rate, overall survival (OS) rate, disease free survival (DFS) rate, hematologic and cytogenetic cumulative incidence of relapse (CIR) were compared among the three groups, the stratified therapy in childhood APL and its correlation with clinical prognosis was analyzed. The statistical analyses were performed by SPSS.

RESULTS: 42 patients were enrolled (median age 5.8 years, range 1.5-14, 64% males and 36% females), 11 in standard-risk group, 18 in intermediate-risk group, 13 in high-risk group. Immunophenotyping analysis indicated that MPO, CD33, CD13 and CD117 were commonly expressed antigens while HLA-DR and CD34 were mostly the negative markers on APL cells. Of the 42 patients receiving treatment, 38 children (90.5%) achieve complete remission. 1 patient from the high risk group died of intracranial hemorrhage, 1 patient from the Standard Risk group died of anthracycline cardiotoxicity, 1 patient from the intermediate group died of severe infection. The estimated overall survival (OS) rates at 3 and 5 years were （74.2±6.7%）and（70±7.4%）respectively, the disease free survival (DFS) rates were（71±3.8%）and（57±8.1%）respectively. The 3 and 5-year cumulative incidence of relapse (CIR) were 18% and 27%. OS for three groups were (86±7.4%),（71±4、8%）and（57±4.7%）respectively, the 5-year DFS were (82±6.3%), (61±5.3%)and(50±7.2%) and 5-year CIR were 6.7%、18%、35%.There were significant differences in 5-year OS, DFS and CIR rates of three groups (P< 0.05).

CONCLUSION: The results indicated that ATRA combined with Anthracycline is effective and safe for treatment of newly diagnosed childhood APL. Prognosis of childhood APL was associated with clinical types. It indicates that stratified therapy according to different risk group can improve the OS and EFS rate and decrease the CIR rate while minimizing chemotherapy-related toxicity. Now, real-time quantitative polymerase chain reaction (RQ-PCR), which can performed to detect PML-RARα fusion transcripts, has become an important means for minimal residual disease (MRD) assays, but it is rarely used in children. Compared with RQ-PCR, clinical risk-adapted classification is a simple, validated and highly predictive index for the determination of stratified therapy in childhood acute promyelocytic leukemia.