Retrospective Study on 46 Chinese Children with Acute Promyelocytic Leukemia: A Single Center Experience in China.

Acute promyelocytic leukemia (APL) is a specific type of hematopoietic malignancy, accounting for ~ 10% of the de novo acute myeloid leukemia (AML). During the old days, severe complications as disseminated intravascular coagulation (DIC) and intracranial hemorrhage were the most common causes of treatment failure after conventional chemotherapy without all-trans retinoic acid (RA). Owing to the application of RA for the induction treatment, the overall survival (OS), the disease free survival (DFS) and the event free survival (EFS) rates have been dramatically improved in adult patients with APL. However, data on long-term outcome of APL in children, especially in Chinese children, have been very limited.

Objective The aim of this study was to investigate the clinical biological features, diagnosis, prognosis and long-term survival in childhood APL.

Methods 46 children (26 boys and 20 girls, aged 1.5 ~13.8 yrs with a median of 9.3 yrs) with APL from April 1998 to October 2005 were enrolled into this study. Immunophenotyping analysis was carried out in 43 patients using multi-parameter flow cytometry. 32 patients went through PML/RARα fusion gene detection using RT-PCR. Induction treatment consisted of ATRA and daunorubicin(DNR) or pirarubicin (THP) followed by 6 courses of multi-drug chemotherapy consolidation and a long-term maintenance therapy including ATRA, high dose Ara-C (HD-Ara-C), DNR+Ara-C (DA), homoharringtonine+Ara-C (HA) and etoposide+Ara-C (EA).

Results Pale, hemorrhage and fever were the most common symptoms in APL patients at the time of presentation. 19 patients (41.3%) were found to have WBC count more than 10.0×10⁹/L at diagnosis. Immunophenotyping analysis showed that CD13, CD33, CD117 and MPO were the most commonly expressed antigens while HLA-DR, CD14 and CD34 were mostly the negative markers on APL cells. 71.9%(23/32) of the patients analyzed were PML/RARα fusion gene positive. Of the 39 patients receiving treatment, 36 children (92.3%) achieved complete remission. 7 children replased during therapy, and 3 relapsed after finishing the entire courses. The 5-year cumulative incidence of relapse (CIR) was 28.6%. The estimated overall survival (OS) rates at one, three and five years were 86.1%, 76.1%and 70.2%, respectively while the event free survival (EFS) rates were 78.4%, 63.6%and 53.1%, respectively. The probability of remaining alive after 5 years for patients with WBC≤10.0×10⁹/L group was 81.4%, significantly higher than those with WBC>10.0×10⁹/L group (51.6%, P=0.026). 5 children with positive PML/RARα S (short) subtype died eventually although all of them achieved CR, which was significantly different from the group with the L (long) subtype (13/13, P=0.001).

Conclusion Induction with ATRA + DNR or THP is an effective and safe therapy for newly diagnosed childhood APL with very high long-term survival rates after 2.5 years of alternative multi-drug chemotherapy and maintenance. High WBC count and S subtype of PML-RARα are the two poor prognostic factors for children with APL.