Abstract
Background: Neoplasms in children are uncommon diseases however they have broad impact on the society. Despite novel therapeutic strategies for children suffering from leukemia or solid tumor, the mortality rate of the disease is still high. The endogenous nitric oxide synthesis inhibitor asymmetrical dimethyl-L-arginine (ADMA) is considered to be a strong cardirovascular risk factor and may lead to new therapeutic strategies. Our previous findings indicate that elevated plasma level of ADMA is correlated with worse prognosis in adult patients with NHL. There are no data available pointing at metabolites of NO-pathway nor clinical evidence as prognostic factor of oncological treatment in children.
Aim: To investigate the relation between elevated plasma level of NO-pathway metabolites and well established markers of clinical stage of the disease.
Material and method: 12 children with acute leukemias (ALL, AML), 13 with solid tumor (PNET, osteosarcoma, Wilms’ tumor, RMS) during hemato-oncological treatment were recruited to a pilot study and N=15 healthy children to a control group. Plasma concentrations of ADMA, SDMA, L-Arg was determined. Relationship to clinical stage of the disease, biochemical and blood markers was tested.
Results Table 1: Differences in mean plasma concentrations of arginine, ADMA and SDMA in pts with leukemia vs pts with solid tumor vs control group
| . | Control:N=15 Mean ±SD . | Median ±SEM . | Leukemia;N=12 Mean±SD . | Median ±SEM . | Solid tumour; N=13 Mean±SD . | Median ±SEM . | P . |
|---|---|---|---|---|---|---|---|
| L-Arg | 68,58±24,29 | 60,19±6,27 | 31,28±8,63 | 30,82±2,49 | 49,59±10,81 | 49,18±3,00 | 0,0000 |
| ADMA | 0,62±0,10 | 0,61±0,02 | 1,17±1,10 | 0,53±0,32 | 0,98±1,10 | 0,46±0,31 | NS |
| SDMA | 0,44±0,18 | 0,39±0,04 | 1,18±1,10 | 0,80±0,32 | 1,56±1,02 | 1,09±0,28 | 0,0024 |
| ARG/ADMA | 112,8±46,28 | 107,4±11,94 | 67,40±54,31 | 69,48±15,68 | 228,82±451,44 | 117,35±125,21 | NS |
| . | Control:N=15 Mean ±SD . | Median ±SEM . | Leukemia;N=12 Mean±SD . | Median ±SEM . | Solid tumour; N=13 Mean±SD . | Median ±SEM . | P . |
|---|---|---|---|---|---|---|---|
| L-Arg | 68,58±24,29 | 60,19±6,27 | 31,28±8,63 | 30,82±2,49 | 49,59±10,81 | 49,18±3,00 | 0,0000 |
| ADMA | 0,62±0,10 | 0,61±0,02 | 1,17±1,10 | 0,53±0,32 | 0,98±1,10 | 0,46±0,31 | NS |
| SDMA | 0,44±0,18 | 0,39±0,04 | 1,18±1,10 | 0,80±0,32 | 1,56±1,02 | 1,09±0,28 | 0,0024 |
| ARG/ADMA | 112,8±46,28 | 107,4±11,94 | 67,40±54,31 | 69,48±15,68 | 228,82±451,44 | 117,35±125,21 | NS |
Table 2:Significant correlations in group of pts with solid tumor and in patients with leukemia
| LEUKEMIA; N=12 . | R . | p . |
|---|---|---|
| ADMA & Ca | 0,78 | 0,008 |
| SDMA & Ca | 0,75 | 0,011 |
| SDMA & CRP | −0,78 | 0,021 |
| Arg/ADMA & K | −0,72 | 0,019 |
| Arg/ADMA & Ca | −0,64 | 0,043 |
| Arg& MONOCYTE | 0,65 | 0,043 |
| ADMA & TOT.BILIRUB. | −0,92 | 0,000 |
| ADMA & TOT.PROTEIN | 0,75 | 0,032 |
| SDMA & EOSINOPHILE | 0,73 | 0,025 |
| SDMA & TOT.BILIRUB | −0,82 | 0,007 |
| Arg/ADMA & TOT.BILIRUB. | 0,81 | 0,009 |
| SOLID TUMOR; N=15 | R | p |
| Arg &RBC | 0,70 | 0,016 |
| Arg & Hb | 0,64 | 0,035 |
| Arg & LYMPHOCYTE | 0,81 | 0,003 |
| Arg & EOSINOPHILE | 0,76 | 0,011 |
| ADMA &MONOCYTE | −0,78 | 0,008 |
| ADMA & TOT.PROTEIN | 0,62 | 0,040 |
| ADMA & Hb | 0,64 | 0,035 |
| Arg/ADMA &MONOCYTE | 0,82 | 0,004 |
| Arg/ADMA & BASOPHILE | 0,65 | 0,043 |
| LEUKEMIA; N=12 . | R . | p . |
|---|---|---|
| ADMA & Ca | 0,78 | 0,008 |
| SDMA & Ca | 0,75 | 0,011 |
| SDMA & CRP | −0,78 | 0,021 |
| Arg/ADMA & K | −0,72 | 0,019 |
| Arg/ADMA & Ca | −0,64 | 0,043 |
| Arg& MONOCYTE | 0,65 | 0,043 |
| ADMA & TOT.BILIRUB. | −0,92 | 0,000 |
| ADMA & TOT.PROTEIN | 0,75 | 0,032 |
| SDMA & EOSINOPHILE | 0,73 | 0,025 |
| SDMA & TOT.BILIRUB | −0,82 | 0,007 |
| Arg/ADMA & TOT.BILIRUB. | 0,81 | 0,009 |
| SOLID TUMOR; N=15 | R | p |
| Arg &RBC | 0,70 | 0,016 |
| Arg & Hb | 0,64 | 0,035 |
| Arg & LYMPHOCYTE | 0,81 | 0,003 |
| Arg & EOSINOPHILE | 0,76 | 0,011 |
| ADMA &MONOCYTE | −0,78 | 0,008 |
| ADMA & TOT.PROTEIN | 0,62 | 0,040 |
| ADMA & Hb | 0,64 | 0,035 |
| Arg/ADMA &MONOCYTE | 0,82 | 0,004 |
| Arg/ADMA & BASOPHILE | 0,65 | 0,043 |
Conclusions:A lower plasma level of L-Arg was found both in pts with leukemia and solid tumors. Higher plasma concentration of SDMA was found in patients with leukemia and solid tumor compared to the control group. Further studies are necessary to clarify the significance of these findings.
Disclosures: No relevant conflicts of interest to declare.
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