Long-term Follow-up And Prognosis Of247Cases Of Children With Acute Lymphoblastic Leukemia

Objective:Retrospective analysis of children with acute lymphoblastic leukemia (ALL) treatment outcome and prognostic factors.Methods:Clinical analysis of332cases of acute lymphocytic leukemia admitted to the hospital from January11th,2005to October30th2008.247patients with effective treatment and included in the survival analysis,85cases not included in the survival analysis as one of following reasons:1.diagnosed as new ALL who accept no treatment or chemotherapy time less than2weeks;2.patients without chemotherapy had died. Treatment protocol:remission induction by VDLD, to consolidate the treatment by2weeks of CAT, prevention of extra-medullary leukemia with3courses of high-dose methotrexate (HD-MTX), early intensification using3continuous courses of VP16+Ara-C every3days, the maintenance phase with VD (VCR+DXM),6-TG+MTX, COAD (only for high-risk groups) outpatient periodically sequential chemotherapy. Outpatient chemotherapy maintained while using VDLD and3consecutive courses of VP16+Ara-C every6months to re-strengthen. Next2cycles of high-dose methotrexate (HD-MTX) prevented extramedullary leukemia until the total number of HD-MTX reached9(low risk group) or11(high risk group). Advanced reinforcement and maintenance therapy until continuous complete remission (CCR) for2.5years (low risk group girl), or3years (high-risk group of girls), or3years (low risk group of boys), or3.5years (high-risk group of boys) and withdrawal.Results:Of the247cases who received effective treatment,235cases obtained complete remission after induction (CR), the CR rate was95.1%.41cases had relapse, including38cases with only bone marrow relapse,1case with CNS leukemia recurrence and testicular leukemia recurrence occurred in2cases and1case with bone marrow, testiclular and CNS leukemia relapse. The total5years accumulative relapse rate was16.6%. The high-risk group had significantly higher recurrence rate than the low risk group (28%and13.7%, P=0.015). In85cases of successful chromosome examination, t (9;22)/Ph chromosome positive, hypodiploid, hyper-diploid were10cases,2cases,10cases,1cases. In the219cases of fusion gene examination TEL/AML1positive, MLL gene rearrangement, BCR/ABL positive were28cases,1cases,10cases, the remaining179cases were negative in all fusion gene. Immuno-phenotyping showed that Pro-B ALL7cases (2.8%), c-ALL161cases (65.2%), Pre-B ALL26cases (10.5%),3cases of B-ALL (1.2%), T-ALL39cases (15.8%),4cases of bi-phenotypic (1.6%),7cases (2.8%) were not determined. Survival analysis of this group of247cases revealed by Kaplan-Meier method that3-years,5-years and7-years of event free survival (EFS) were76.7±2.7%,75.4±2.8%and75.4±2.8%.3-years event free survival (EFS) of the low risk group (n=167), medium risk group (n=30), high risk group (n=50) were82.4±3%,66.7±8.6%,60.9±7%,5-years EFS were81±3.1%,63±8.9%,60.9±7%. Long-term EFSs of medium-risk and high-risk group were significantly lower than those of low risk group (P=0.028,0.004).Univariate analysis of prognostic factors showed that t (9;22)/Ph chromosome/BCR/ABL positive, hypo-diploid, hyper-diploid chromosome positive, MLL gene rearrangement, T-ALL, gender, CD13and CD33positive were not significantly associated with long-term EFS; while TEL/AML1positive,15-days successful induction,28-days successful induction, good economic condition (with medical insurance or urban registered permanent residents), age between1-10years old, initial white blood cell count<100×109/L were good prognosis factors for long-term survival of ALL(P=0.034.0.031,0.003、0.000.0.039.0.000). Multivariate Cox regression analysis showed the successful induction at28days (RR=1.743,P=0.035) and initial WBC<100×109/L (RR=2.5,P=0.001) are long-term EFS independent favorable prognostic factors.Conclusions:5-years EFSs of low-risk, medium-risk and high-risk group of children with ALL were81±3.1%,63±8.9%,60.9±7%. TEL/AML1positive,15-days successful induction,28-days successful induction, good economic condition, age between1-10years old, initial white blood cell count<100×109/L were good prognostic factors of ALL, while initial leukocyte count and the response to induction had important significance for the prognosis of ALL.