Correlation of karyotype and immunophenotype in childhood acute lymphoblastic leukemia; experience at the national cancer institute, Cairo University, Egypt

To identify chromosomal pattern among the major immunophenotypic subgroups in Egyptian children with ALL, and its correlation with clinical presentation and disease free survival. Cytogenetic and immunophenotypic analysis were done for all patients. Patients received ALL-PNCI-III/98 chemotherapy protocol used at NCI, Cairo University. The frequency of pseudodiploidy and normal karyotype in the whole group was 42.9% and 33.3% respectively. The frequency of pseudodiploidy was 36.8% in CALLA positive early pre B, 30.7% in pre B cases, 71.4% in T cell cases and 100% in mature B cell cases. At 12 months, DFS was 50% for pseudodiploid group having pre B phenotype, compared to 16.6% for pseudodiploid group with CALLA positive early pre B ALL. Sixteen percent of the studied cases showed T cell phenotype, 71.4% of them showed pseudodiploid karyotype, all of them had high risk features. Hyperdiploidy was found in 31.5% of CALLA positive early pre B cases and was associated with favorable prognostic features and DFS of 66.6% at 12 months. Hyperdiploidy of >50 chromosome represented 62.5% of hyperdipoid cases, 80% of them were CALLA positive early pre B ALL carrying good risk features. Fifty percent of normal karyotypic patients showed pre B phenotype, while 42.8% showed CALLA positive early pre B ALL. Their age, TLC, DFS, were almost comparable. CALLA early pre B phenotype has a positive impact on chromosomal pattern having best outcome among patients with hyperdiploidy. The Pseudodiploid karyotype carries a better outcome with pre B phenotype

Study of the expression of survivin and mutant p53 in pediatric acute lymphoblastic leukemia

Childhood acute lymphoblastic leukemia is the most common malignancy in children with a yearly incidence of 31/1000000 children younger than 15 years old. The peak incidence of childhood ALL is between 3 and 6 years of age with male predominance. The relative frequency of pediatric ALL in the NCI-Cairo University is 35.5% for the years 2003-2004. In this study survivin and mutant p53 expressions were studied in 64 newly diagnosed pediatric ALL patients. Their associations to the different prognostic factors of ALL and their association to each other were studied. In this study, 21 out of 64 ALL cases [32.8%] showed positive expression of survivin [17 patients were moderately positive, 2 patients were strong positive and 2 patients were weak positive] and 24 out of 64 studied ALL cases [37.5%] demonstrated positive expression of p53 [20 patients were strong positive, 3 patients were moderately positive and 1 patient was weak positive]. On comparing survivin expression with the different prognostic factors of ALL, the results were statistically significant as regards the percentage of blasts in the peripheral blood [p-value = 0.0068], and the percentage of blasts in the bone marrow [p-value = 0.05]. As regards LDH, ALP, and uric acid serum concentrations, no statistically significant differences were found [p-value = 0.154, 0.52 and 0.41 respectively]. No significant association was found between survivin expression and hepatosplenomegaly. As regards p53 expression compared with the different prognostic factors no statistically significant results were found. According to immunophenotyping [IPT], survivin was positive in 5 out of 14 cases [35.7%] of proB-ALL, 0% [0/11] C-ALL, 29.2% [7/24] preB-ALL, 75% [6/8] mature B-ALL and 42.9%[3/7] T-ALL. The results were statistically significant [p-value = 0.046], while p53 was positive in 4 out of 14 cases [28.5%] of proB-ALL, 36.4% [4/11] C-ALL, 41.6% [10/24] preB-ALL, 50% [4/8] mature B-ALL and 28.6% [2/7] T-ALL. The results were statistically non significant. No significant correlation was found between survivin and p53 expression in the studied ALL cases [p-value = 0.872]. In this study, a total of 23 patients successfully completed induction phase. All of them achieved complete remission. Two patients developed isolated bone marrow relapse at a median period of 7.5 months. The disease free survival for the 23 patients was 89.6% at a median of 11 months. The DFS for P53 positive [12/23] and p53 negative [11/23] patients was 91.7% and 90.9% respectively [p= 0.90]. The DFS for survivin positive [11/23] and survivin negative [12/23] patients was 85.7% and 93.7% respectively [p=0.49]. In conclusion, we could not find any association between p53 and survivin expressions and the different prognostic factors of pediatric ALL patients, [the only statistically significant results were obtained when comparing the blast count% in both the peripheral blood, and the bone marrow between survivin positive and survivin negative cases]. As regards the comparison of survivin expression and phenotyping of the studied patients, it was not expressed in C-ALL cases which are known to have a good prognosis. Further we could not decide whether positive p53 or survivin in ALL patients had an impact on DFS. Further studies with larger number of patients and longer duration of follow up are recommended to throw more light on the significance of p53 and survivin in relation to ALL patients