Background: Despite improvements achieving complete remission and progress in supportive care of children with acute leukemias or solid tumors during the last decade, there are no optimal prognostic markers in stratification of risk of adverse events leading to poor outcome. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is associated with atherosclerosis and represents an independent marker for cardiovascular morbidity and mortality.

Aim: To investigate the clinical significance of methylarginines in leukemia and solid tumors in children.

Material and method: Concentration of metabolites of nitric-oxide pathway in children during therapy of acute leukemia (ALL) – N 12 and solid tumors N 15 (osteosarcoma, RMS, PNET, Wilms’ tumor) was determined. Correlations of biochemical markers, blood count parameters and plasma level of methylarginines were investigated. In addition, the influence of cytostatics on NO-pathway metabolites was analyzed.

Results: Table 1: Differences in mean plasma concentration of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor

Leukemia N=12 Mean ±SDMedian±SEMSolid tumor N=15 Mean ±SDMedian±SEMp
Arg 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0003 
ADMA 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS 
SDMA 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 NS 
Arg/ADMA 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS 
Leukemia N=12 Mean ±SDMedian±SEMSolid tumor N=15 Mean ±SDMedian±SEMp
Arg 31,28±8,63 30,82±2,49 49,59±10,81 49,18±3,00 0,0003 
ADMA 1,17±1,10 0,53±0,32 0,98±1,10 0,46±0,31 NS 
SDMA 1,18±1,10 0,80±0,32 1,56±1,02 1,09±0,28 NS 
Arg/ADMA 67,40±54,31 69,48±15,68 228,82±451,44 117,35±125,21 NS 
View Large

Table.2. Differences in mean plasma concentrations of arginine, ADMA and SDMA depending on gender, treatment, etc.

N=27ArginineADMASDMAArg/ADMA
Sex 1. Mail; 2. Femail 1. 0.NS NS NS NS 
HSCT (1-yes; 0-no) 1. 0.NS NS NS NS 
Remission (1-yes; 0-no) 1. 0.NS NS NS NS 
Currently infection (1-yes; 0-no) 1. 0.NS NS NS NS 
Glucocoricoids (1-yes; 0-no) 1. 31,9±9,30. 51,0±11,2 p=0,0011 NS NS NS 
Cytostatic – any (1-yes; 0-no) 1. 0. NS NS NS NS 
Doxorubicine (1-yes; 0-no) 1. 0. NS NS NS NS 
Vincristine (1-yes; 0-no) 1. 0. NS NS NS NS 
Cytarabine (1-yes; 0-no) 1. 32,0±10,50. 45,6±10,8 p=0,022 NS NS NS 
Methotrexate (1-yes; 0-no) 1.0 NS NS NS NS 
Thioguanine/6-merkaptopurine(1-yes; 0-no) 1. 0. NS NS NS NS 
Cyclophosphamide/Iphosphamide(1-yes; 0-no) 1. 0. NS NS NS NS 
N=27ArginineADMASDMAArg/ADMA
Sex 1. Mail; 2. Femail 1. 0.NS NS NS NS 
HSCT (1-yes; 0-no) 1. 0.NS NS NS NS 
Remission (1-yes; 0-no) 1. 0.NS NS NS NS 
Currently infection (1-yes; 0-no) 1. 0.NS NS NS NS 
Glucocoricoids (1-yes; 0-no) 1. 31,9±9,30. 51,0±11,2 p=0,0011 NS NS NS 
Cytostatic – any (1-yes; 0-no) 1. 0. NS NS NS NS 
Doxorubicine (1-yes; 0-no) 1. 0. NS NS NS NS 
Vincristine (1-yes; 0-no) 1. 0. NS NS NS NS 
Cytarabine (1-yes; 0-no) 1. 32,0±10,50. 45,6±10,8 p=0,022 NS NS NS 
Methotrexate (1-yes; 0-no) 1.0 NS NS NS NS 
Thioguanine/6-merkaptopurine(1-yes; 0-no) 1. 0. NS NS NS NS 
Cyclophosphamide/Iphosphamide(1-yes; 0-no) 1. 0. NS NS NS NS 
View Large

Conclusions: Plasma level of L-Arg was significantly higher in patients with solid tumor The L-Arg/ADMA ratio was not significantly higher in patients with solid tumors and lower plasma level of ADMA was found. Treatment with glucocorticoids and cytarabine was associated with significantly lower level of L-Arg. No significant treatment dependent difference was found in level of nitric oxide metabolic pathway.

Topics:
leukemia, solid tumors, n,n-dimethylarginine, arginine, nitric oxide, brachial plexus neuritis, cytarabine, leukemia, acute, metabolites, adverse event

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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