Prognostic Value Of Detection Of Lymphoblasts In The Period Of Early Treatment In Childhood Acute Lymphoblastic Leukemia

Objective:The leukemia is the most common disease of childhood malignant tumors,Of which acute lymphoblastic leukemia(ALL) is most common. The cure rate of childhood with ALL who were treated in contemporary risk-adapted therpy has been improved significantly. In virtually all clinical trials, risk classification are based on clinical and biological features such as age, leukocyte count, immunophenotype,and the presence of specific chromosome aberrations at diagnosis as well as early response to therapy. But there is no unified criterion of Risk classification. Response to therapy,which reflects the genetics of leukemia cells and the pharmacodynamics and pharmacogenetics of the host,has greater prognostic strength than does any other biologic or clinical feature tested to date.In order to evaluate the relationship between early response to therapy and the ultimate outcome ,a retrospective analysis was carried out to evaluate patients diagnosed with childhood ALL who were treated with the 04 Protocol(suggested by the Pediatric Hematology Group of China Medical Association in 2004)in the past 4 years.Methods:88 children with newly diagnosed ALL were enrolled in the 04 protocol.Blasts in peripheral blood(PB)on day 8(D8),the ration of blasts in bone marrow(BM)on day 19(D19)and on day 33(D33)were examined.On D8,the patients were divided into 2 groups according to the blasts in PB:group with the number of blast cells <0.05(PGR)and group with the number of blast cells <0.05(PPR).On D19,the patients were divided into 3 groups according to the blasts in BM:group with the number of blast cells <0.05(M1),group with the number of blasts between 0.05 and 0.25(M2)and group with the number of blasts≥0.25(M3).On D33,the patients were divided into 3 groups according to the blasts in BM:group with the number of blast cells <0.05(CR),group with the number of blasts between 0.05 and 0.25(PR)and group with the number of blasts≥0.25(NR).The event-free survival(EFS)was estimated by Kaplan-Meier analysis.Log-rank test was used to compare the 4-year EFS of different groups.The differences in the biological features were compared by Chi-square analysis or Fisher exact test.The correlation of the biological features were analyzed by correlate analysis.The influence of potential prognostic factors on EFS was estimated with the Cox proportional hazard model.Results: 1 The rate of the patients with T-ALL was significantly higher in the group of PPR than those in the group of PGR [37.5% vs 8.45%(P=0.044)];The number of blasts in PB on D8 was correlated with white blood cell(WBC)counts in PB at diagnosis(Spearman correlation coefficient : r=0.279 , P=0.009 ) and T-ALL ( Spearman correlation coefficient:r=0.276,P=0.014)significantly.The number of blasts in BM on D19 was correlated with the number of blasts in PB on D8(Spearman correlation coefficient r=0.318,P=0.005)significantly.The ration the patients with CR on D33 was not correlated with the number of blasts on D19 and the number of blasts in PB on D8(P>0.05).2 No significant difference was found in 4-year's EFS for patients with PPR compared with those with PGR [50%±25% vs 54.97%±8.65%(P=0.9013)].3 In regard to the bone marrow response on D19,no significant differences were found in 4-year's EFS for the patients in M1,M2 and M3 [4-year EFS for these groups were 56.23%±11.41%,65.57%±13.71% and 50%±30.36%,respectively.P=0.52].4 The 4-year's EFS for the patients with complete remission(CR)on day 33 was 68.7%±6.75%.Of the 5 patients who achieved PCR on day 33,1 relapsed after 29 months,4 other patients lost in the follow up,1 patient with non-remission(NR)also lost in the follow up.5 Multiple factor analysis showed that the marrow status on D19 is an independent prognostic factor for childhood ALL.Conclusions:1 The number of blasts in PB on D8 was correlated with WBC counts in PB at diagnosis and T-ALL significantly.The number of blasts in BM on D19 was correlated with the number of blasts in PB on D8 significantly.2 The patients with PPR who received the augmented regimen achieved CR,but they were prone to relapse and need intensive therapy.The patients with M2 or M3 marrows on D19 who received the augmented regimen achieved CR,but they were prone to relapse and need intensive therapy.3 Multiple factor analysis showed that the marrow status on D19 is an independent prognostic factor for childhood ALL.4 The prednisone response and marrow status on D19 and on D33 were not always consistent , they had different information in estimating outcome.so we had better to estimate the early treatment response and predict outcome by combining them.