The Preliminary Study On The Prognosis And The Expression Of Aven Gene In Childhood Acute Lymphoblastic Leukemia

Part 1 The relationship among the prognosis and MICM subtypes,clinical features of childhood acute lymphoblastic leukemiaObjective To obtain theoretical evidence for individual therapy and further improving thequality of life of long-term survivors, we explore the relationship among the prognosis andMICM subtypes, clinical features and main chemotherapeutics.Methods A retrospective analysis was carried out on the childhood ALL treated in ourinstitute from January 1998 to April 2007. EFS curves were calculated by using theKaplan-Meier method and were compared with the log-rank test, Statistics was done bySPSS 13.0.Results Out of the 115 patients, 90.4% attained complete remission (CR) in a median timeof 34 days. 5 died after induction remission (2 from fungal sepsis, 3 from bacterial sepsis leading to disseminated intravascular coagulation). The overall EFS rate at 5 years was(69.0±5.0) % with median observation duration of 21 months. The EFS rates at 5 years inlow-risk (LR), median-risk (MR) and high-risk (HR) groups were (82.0±6.0) %, (77.0±15.0) % and (43.0±11.0) %, respectively (P＜0.05). Relapse occurred in 14 patients(12.2%)in a median time of 17 months, including 11 hematological relapses, 1 isolated centralnervous system (CNS) relapse, 1 testicular leukemia combined with second malignancy(acute myeloid leukemia),1 bone marrow combined with CNS relapse, 1 second lymphomaafter allogeneic transplantation. Eliminating cranial irradiation in all the patients, theoccurrence rate of CNS relapse was not higher than previously reported. Independentadverse prognostic factors included risk group, t (9; 22)/bcr-abl and leukocyte count ofdiagnosis.Conclusions The EFS rate in our institute was similar to those in developed countries, t (9;22)/bcr/abl was the most important adverse independent prognostic factor. In the context ofeffective systemic and intrathecal chemotherapy, cranial irradiation can be eliminated in allpatients. Part 2 Expression and clinical significance of antiapoptotic geneAven in childhood acute lymphoblastic leukemiaObjective To explore the expression of antiapoptotic gene Aven in childhood ALL and itsrelationship with clinical features of ALL.Methods RT-PCR was used to detect the expression of Aven mRNA in 55 cases ofchildhood ALL. The control group included 11 childhood patients with no malignanthematological diseases.Results Aven mRNA expression was found to be higher in patients =10 years old and wasalso significantly higher in relapsed patients. Univariate and multivariate analysis indicatedthat Aven overexpression was an independent poor prognostic factor.Conclusions Aven mRNA expression is abnormal in childhood ALL and is associated withthe clinical classification of childhood ALL. It is suggested that Aven gene expression maypredict prognosis in childhood ALL. Part 3 Autogeneic dendritic-cell-activated and cytokine induced killercells therapy for the treatment of childhood acute leukemia previouslygiven chemotherapyObjective To investigate the effect and safety of the therapy of autogeneicdendritic-cell-activated and cytokine induced killer cells (DC-C1K) cultured in vitro for thetreatment of childhood acute leukemia previously given chemotherapy.Methods Autogeneic DC-CIK were transfused to the patients twice after cultivation andamplification in vitro, then thymic peptide were injected subcutaneously at 10mg/d, everyother day for ten times. The side effects were observed during the treatment andhematological and genetic changes were monitored regularly after treatment.Results 5 patients (3 AML and 2 ALL) were treated with DC-CIK therapy and 9case-times were conducted successfully. Chill and fever appeared in 6 case-times duringthe transfusion and disappeared immediately after non-specific treatment. During thetreatment, no other side effects appeared and no changes of ECG and liver-renal functiontook place. Abnormal chromosome t (8; 21) disappeared in 1 case after one course oftherapy and all of the patients remain hematological and chromosomal remission. 4 patientsremained event-free-survival for half and three years, two years, two years and one yearrespectively since last follow-up. 1 AML patient relapsed two years later who did notundergo total course of chemotherapy.Conclusions It seems safe to treat childhood AL by autogeneic DC-CIK therapy previouslygiven chemotherapy with mild side effects and short-term therapeutic effect. Furtherlarge-scale clinical randomized comparison needs to be carried out to investigate whetherautogeneic DC-CIK could efficiently reduce the relapse risk of childhood AL after totalcourse of chemotherapy.