Elevated asymmetric dimethylarginine in young adult survivors of childhood acute lymphoblastic leukemia: A preliminary report

Article type: Research Article

Authors: Sulicka, Joanna^; | Surdacki, Andrzej^; | Strach, Magdalena^; | Kwater, Aleksander^; | Gryglewska, Barbara^; | Ćwiklińska, Magdalena^; | Balwierz, Walentyna^; | Grodzicki, Tomasz K.^;

Affiliations: Department of Internal Medicine and Gerontology, Faculty of Medicine, Jagiellonian University, Cracow, Poland | 2nd Department of Cardiology, Faculty of Medicine, Jagiellonian University, Cracow, Poland | Department of Pediatric Oncology and Hematology, Polish-American Institute of Pediatrics, Faculty of Medicine, Jagiellonian University, Cracow, Poland | University Hospital, Cracow, Poland | University Children's Hospital, Cracow, Poland

Note: [] Corresponding author: Andrzej Surdacki, MD, FESC, 2nd Department of Cardiology, Jagiellonian University, 17 Kopernika Street, 31-501 Cracow, Poland. Tel.: +48 12 4247180; Fax: +48 12 6368 039; E-mail: [email protected]

Abstract: Background: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy. Methods: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18–28 years) who had survived without recurrent disease ⩾ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20–31 years). Results: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μ mol/L; p=0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 � 0.16; p=0.004). The effect of former ALL on ADMA was attenuated (intergroup p=0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: −0.065 ± 0.030 [SEM]; p=0.03). Conclusions: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.

Keywords: Acute lymphoblastic leukemia, asymmetric dimethylarginine, late effects, long-term survivors of childhood malignancy

DOI: 10.3233/DMA-2012-0906

Journal: Disease Markers, vol. 33, no. 2, pp. 69-76, 2012