[Clinical Characteristics and Treatment Efficacy of Children with SIL/TAL1 Positive T-Cell Acute Lymphoblastic Leukemia].

OBJECTIVE: To investigate the clinical features, treatment and prognosis of children with SIL-TAL1 fusion gene positive T-cell acute lymphoblastic leukemia (T-ALL). METHODS: The data of 101 children with T-ALL were collected from April 2005 to November 2012 in Beijing Children's Hospital. The common clinical features, early treatment response, minimal residual disease (MRD), event-free survival (EFS) and relapse-free survival (RFS) were compared between children with SIL-TAL1 positive and negative T-ALL. The treatment efficacy in children with SIL-TAL1 positive T-ALL was compared between BCH-2003 and CCLG-2008 protocol. RESULTS: Out of 101 cases, 22 cases (21.9%) of T-ALL carried SIL-TAL1 fusion gene. The distribution of sex, age, response to prednisone and central nervous system (CNS) involvement were no significant different at diagnosis between SIL-TAL1 positive and negetive patients. However, the WBC count in SIL-TAL1 positive cases were significantly higher than that of SIL-TAL1 negative cases at diagnosis (P<0.05). Additionally, MRD levels were not significantly different between children with SIL-TAL1 positive or negative T-ALL at 3 time points including: after the remission induction therapy, before delayed intensive therapy II and before maintenance therapy. However, the number of cases with high MRD levels before consolidation therapy were more in SIL-TAL1 positive group than that in SIL-TAL1 negative group (P<0.05). The cases with high MRD levels before delayed intensive therapy I was more in SIL-TAL1 negative group than that in the SIL-TAL1 positive group (P>0.05). Besides, there were no significant differences in 5-year EFS and RFS between the two groups. The risk of 22 children with SIL-TAL1 positive acute T-ALL was again stratified according to the typing stemdard in CCLG-2008 protocol, as a result, the risk in BCH-2003 group (10 cases) was significantly higher than that in BCH-2008 group (12 cases) (P<0.05), but no significant difference was found in common clinical features, early treatment response, MRD levels and treatment efficacy. CONCLUSIONS: Although WBC level was significantly higher in SIL-TAL1 positive group than that in SIL-TAL1 negative group, the treatment efficacy in SIL-TAL1 positive group was similar to SIL-TAL1 negative group. Meanwhile, the children with SIL-TAL1+ T-ALL may respond poorly to early intensive therapy, the BCH-2003 protocol may be more suitable for the patients with this subtype of leukemia.

[Comparison of the efficacy of two chemotherapy protocols for children with TEL-AML1[STBZ] fusion gene positive acute lymphoblastic leukemia].

This study was aimed to compare the curative effect of BCH - 2003 protocol and CCLG - 2008 protocol for children with TEL-AML1 fusion gene positive childhood acute lymphoblastic leukemia (ALL) and to investigate the more suitable protocol for this subtype of childhood leukemia. The clinical data for children with TEL-AML1 fusion gene positive ALL admitted from January 2003 to October 2010 in Hematology Center of Beijing Children's Hospital were collected. The common clinical characteristics including prednisone response at day 8, minimal residual disease (MRD) at the end of induction of remission (day 33), event free survival (EFS), relapse free survival (RFS) were compared. The results showed that out of 204 children with TEL-AML1 fusion gene positive ALL, 134 and 70 patients were treated by BCH-2003 protocol and CCLG-2008 protocol respectively. There were no statistical difference in age, white blood cell count in peripheral blood at presentation, prednisone response and CNS involvement. However, there were more boys in CCLG-2008 group (P = 0.025). The negative rate of MRD at day 33 in BCH-2003 group was lower than that in CCLG-2008 group (P = 0.013). After re-stratifying the patients in CCLG-2008 group according to the stratification criteria of BCH-2003 protocol, the negative rate of MRD at day 33 of patients with intermediate risk remained higher in BCH-2003 group than that in CCLG-2008 group (P = 0.014) . However, no significant difference in the patients with standard risk was found. There were also no significant statistical differences in the incidence of severe infection, EFS and RFS, (P = 1.000, P = 0.327,P = 0.251 respectively) during chemotherapy. It is concluded that for children with TEL-AML1 fusion gene positive ALL, the induction of remission of BCH - 2003 protocol can decrease leukemic load more quickly than that of CCLG - 2008 protocol. However, the outcome of the patients treated by the two protocols is similar.

[Evaluation of the efficacy of two successive protocols on pediatric acute lymphoblastic leukemia with E2A-PBX1 fusion gene].

OBJECTIVE: To evaluate the efficacy of BCH-03 and CCLG-08 protocols in treating E2A-PBX1 pediatric acute lymphoblastic leukemia (ALL). METHOD: From January 2003 to January 2011, 59 ALL patients identified as E2A-PBX1 were analyzed in a retrospective study. There were 37 and 22 patients treated with Protocol BCH-03 and CCLG-08, respectively. The clinical characteristics at diagnosis, response to early treatment, the time of relapse, relapse-free survival (RFS) and event-free survival (EFS) in the two groups were analyzed. RESULT: There were no significant differences in gender, age, initial white blood cell count, the central nervous system involvement, immunophenotype, prednisone response, the rate of complete remission, and the time of relapse between the two groups (P > 0.05). The only difference in induction therapy of the two protocols existed in the glucocorticoids used, that is, BCH-03 used 60 mg/m(2) prednisolone and CCLG-08 used 6 mg/m(2) dexamethasone. The doses of vincristine, daunorubicin and L-asparaginase were the same in the two groups. At the end of induction therapy, the MRD negativity rate in BCH-03 group was significantly higher than that in CCLG-08 group (84.2% vs. 47.1%, P = 0.018). The incidences of severe infection of the two groups during induction of remission were similar (P = 0.135). The EFS of BCH-03 group was significantly superior to that of CCLG-08 group (94.5% vs. 71.5%, P = 0.010), and the RFS of BCH-03 group tended to be better than that of CCLG-08 group (94.5% vs. 78.6%, P = 0.059). CONCLUSION: Compared to Protocol CCLG-08, Protocol BCH-03 was more effective for pediatric E2A-PBX1 ALL, and 60 mg/m(2) prednisolone was more suitable for the induction therapy of this subtype of pediatric ALL.

[Treatment with combined all-trans retinoic acid and anthracycline of 37 children with acute promyelocytic leukemia].

OBJECTIVE: To study the clinical features of childhood acute promyelocytic leukemia (APL) and to analyze the survival and prognostic factors and efficacy and safety of combined treatment with all-trans retinoic acid (ATRA) and anthracycline. METHOD: The clinical features of 37 children with newly diagnosed APL hospitalized in our center during January 2005 to February 2009 were retrospectively analyzed. RESULT: Thirty percent of patients were at low risk, 43% patients were at intermediate risk, 27% patients were at high risk. Sixty percent of patients had DIC. Retinoic acid syndrome (RAS) was present in 2 patients (6%). Death during induction occurred in 3 patients (8%). Complete remission (CR) was achieved in 83.7% of patients. The patients in high risk group had higher risk than those in intermediate and low risk group (P = 0.029). The time to achieve CR was not significantly different (P = 0.612). Idarubicin had no advantage compared with daunorubicin in time to achieve CR (P = 0.628). Survival rates were calculated using Kaplan-Meier statistical method, and 2 years event-free survival (EFS) rate was 81%, the 2-year EFS rate was 100% for low-risk group, 81% for intermediate-risk group, and 60% for high-risk group. CONCLUSION: Using combined chemotherapy with ATRA and anthracyclines had the following advantages: high CR rate, high long-time survival rate and low side effect. DIC remained the main complication among patients receiving induction treatment. Initial WBC count and platelet count are important prognostic factors which might be useful in prognostication and treatment planning.

[Relation between TEL-AML1 expression level and clinical characteristics as well as early response to treatment in children with acute lymphoblastic leukemia].

The study was aimed to investigate the relation between the expression level of TEL-AML1 (translocation ETS leukemia-acute myeloid leukemia 1) fusion gene and clinical characteristics as well as early response to treatment in children with ALL (acute lymphoblastic leukemia). With real-time quantitative polymerase chain reaction (RQ-PCR), the expression level of TEL-AML1 at diagnosis and MRD (minimal residual disease) at the end of induction of remission were detected in 35 children with ALL, including 20 SR (standard risk) and 15 IR (intermediate risk) patients. The expression level of TEL-AML1 and clinical characteristics at diagnosis were compared between MRD negative and MRD positive patients. The relation between TEL-AML1 expression levels at diagnosis, MRD level and clinical characteristics as well as early response to treatment were also explored. The results indicated that the expression levels of TEL-AML1 at diagnosis were 1.63 x 10(4) copies/10(4) copies ABL (median). At the end of induction of remission, 16 patients (10 SR and 6 IR patients) did not achieve molecular remission, whose MRD levels were 0.84 - 282.93 copies/10(4) copies ABL. No relation was found between expression levels of TEL-AML1 at diagnosis and clinical characteristics as well as MRD level. There was a significant relation between MRD level and blast count in peripheral blood (PB) at day 8 after prednisone trial induction. Significant relations between MRD level and presenting leukocyte count, blast percentage in PB were also found in the patients with presenting leukocyte count < 25 x 10(9)/L. TEL-AML1 expression level at diagnosis of MRD negative patients was lower than that of MRD positive ones. It is concluded that therapy after induction of remission is of importance by the fact that 45.71% children with TEL-AML1(+) ALL did not achieve molecular remission at the end of induction of remission. The effectiveness of prednisone trial predicts the MRD level. In addition, presenting leukocyte count, blast percentage in PB and TEL-AML1 expression level at diagnosis may have an effect on MRD level to some extent.

[Analysis of 21 children with acute non-lymphoid leukemia carrying AML1/ETO fusion gene].

OBJECTIVE: It was revealed that t(8; 21) (q22; q22) was one of the most common chromosomal aberrations in acute non-lymphoid leukemia. The translocation was found to be involved in the AML1 gene on the chromosome 21 and the ETO gene on the chromosome 8, and resulted in the formation of AML1/ETO fusion gene on the derivative chromosome 8. The fusion gene was a transcription factor and played a direct role in the leukemogenesis. The translocation was mainly observed in M(2), accidentally in M(4) and M(1) and rarely in MDS. Here we studied the main clinical data in children with acute non-lymphoid leukemia (ANLL) carrying the AML1/ETO fusion gene. In addition, we discussed the significance of the detection of AML1/ETO fusion gene in the diagnosis and prognosis of children with ANLL. METHODS: The authors investigated 29 patients in our hospital from December 2000 to March 2002. The patients were divided into two groups. Group A included 21 patients, 14 males and 7 females. They were 3.6 to 14 years old and the median was 9. Group B included 8 patients, 6 males and 2 females. They were 0.8 to 14 years old and the median was 6. Diagnosis was made according to FAB and MIC criteria and the expression of AML1/ETO fusion gene was detected with nested RT-PCR. The patients were treated according to DA, DAE or BFM regimen, respectively. The main clinical indexes including age, Hb, white blood count, platelet, blasts in PBC and BM, and time of arrival at complete remission (CR), were compared statistically between the two groups with t test of independent samples. RESULTS: All the 21 patients in group A were found carrying AML1/ETO, and 17 patients (81%) were classified as M(2), the other 4 cases were of M(2) developed from MDS-RAEB-T, M(4Eo), M(5) and eosinophil leukemia, respectively. Eighteen out of 20 patients whose effects could be assessed reached CR, and the CR ratio was 90%. Two patients in group B were of AML-M(1), 3 M(2), 1 M(3), 1 M(4), and 1 M(5), respectively. None of them was found carrying AML1/ETO. Seven cases reached CR and the ratio was 87.5%. There was no significant difference between the two groups in the above clinical indices. CONCLUSIONS: Between the two groups of patients there was no significant difference in the above clinical indices. RT-PCR for the detection of AML1/ETO in children with ANLL was quick, convenient and sensitive, and could be regarded as a useful method for the diagnosis and prognosis of ANLL.