BACKGROUND: The purpose of our study was to determine whether spontaneous and post-initial therapy apoptosis indexes (AI) and the intracellular pH of blasts have prognostic value in the treatment of children with acute leukemia. MATERIAL/ METHODS: Blasts from 38 children with acute leukemia (31 with ALL and 7 with AML) were tested for apoptotic index (Annexin V) and intracellular pH (SNARF). Of the ALL patients, 9 were low risk, 7 medium risk, and 15 high risk. Among the AML patients, 1 was low risk and 6 were high risk. Follow-up ranged from 6 to 120 weeks (median 60 weeks). RESULTS: The mean spontaneous AI was 19 +/-16%. The pH of leukemic blasts before treatment varied between 6.6 and 7.9 (mean 7.2 +/- 0.5). For patients < 10 years old, the markers for good prognosis were a WBC count below 50 x 10(3)/microml, good response to prednisone therapy at day 8, and remission at or before day 33. Univariate analysis showed that pH < 7 had favorable prognostic significance. Overall, the probability of EFS for patients with pH < 7 was 1.0, as opposed to 0.49 for those with pH > 7 (p=0.049, n=36). The probability of EFS for patients with AI below the median was not significantly different from those with AI above the median (0.4 vs 1.0, NS). CONCLUSIONS: The assessment of intracellular pH in blasts may be an important prognosticator for ALL patients. Children with low spontaneous AI or high pH of leukemic blasts appear to have an unfavorable prognosis.
BACKGROUND: The purpose of our study was to determine whether spontaneous and post-initial therapy apoptosis indexes (AI) and the intracellular pH of blasts have prognostic value in the treatment of children with acute leukemia. MATERIAL/ METHODS: Blasts from 38 children with acute leukemia (31 with ALL and 7 with AML) were tested for apoptotic index (Annexin V) and intracellular pH (SNARF). Of the ALL patients, 9 were low risk, 7 medium risk, and 15 high risk. Among the AMLpatients, 1 was low risk and 6 were high risk. Follow-up ranged from 6 to 120 weeks (median 60 weeks). RESULTS: The mean spontaneous AI was 19 +/-16%. The pH of leukemic blasts before treatment varied between 6.6 and 7.9 (mean 7.2 +/- 0.5). For patients < 10 years old, the markers for good prognosis were a WBC count below 50 x 10(3)/microml, good response to prednisone therapy at day 8, and remission at or before day 33. Univariate analysis showed that pH < 7 had favorable prognostic significance. Overall, the probability of EFS for patients with pH < 7 was 1.0, as opposed to 0.49 for those with pH > 7 (p=0.049, n=36). The probability of EFS for patients with AI below the median was not significantly different from those with AI above the median (0.4 vs 1.0, NS). CONCLUSIONS: The assessment of intracellular pH in blasts may be an important prognosticator for ALL patients. Children with low spontaneous AI or high pH of leukemic blasts appear to have an unfavorable prognosis.
Authors: Tapas Manna; Douglas A Thrower; Srinivas Honnappa; Michel O Steinmetz; Leslie Wilson Journal: J Biol Chem Date: 2009-04-08 Impact factor: 5.157