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Purpose: Methotrexate (MTX)/6-Mercaptopurine (6MP)-based maintenance therapy is crucial to cure childhood acute lymphoblastic leukemia (ALL). Cytotoxicity is mediated by incorporation of thioguanine nucleotides (TGN) into DNA (DNA-TG) with higher levels in leucocytes being associated with reduced relapse risk. To further understand the dynamics of DNA-TG formation, we measured DNA-TG levels in leucocyte subsets during maintenance therapy and in the months following its discontinuation.Methods: DNA-TG levels were measured in leucocytes (DNA-TGTotal), polymorph nucleated granulocytes (neutrophils, eosinophils, basophils [DNA-TGPMN]) and mononucleated cells (lymphocytes, monocytes [DNA-TGMNC]) in 1013 samples from 52 patients on ALL maintenance therapy (951 samples during therapy and 62 samples after therapy discontinuation, respectively).Results: Median DNA-TGTotal, DNA-TGPMN and DNA-TGMNC during maintenance therapy were 539, 563 and 384 fmol/µg DNA, respectively. DNA-TGPMN displayed more pronounced fluctuation than DNA-TGMNC (range 0-3084 [interquartile range IQR 271-881] versus 30-1411 [IQR 270-509] fmol/µg DNA). DNA-TGTotal was more strongly correlated with DNA-TGPMN (rS = 0.95, p < 0.0001) than DNA-TGMNC (rS = 0.73, p < 0.0001). DNA-TGPMN correlated less with DNA-TGMNC (rS = 0.64, p < 0.0001) and to a much lesser extent with absolute neutrophil count (rS = 0.35, p < 0.0001). Following discontinuation of therapy, DNA-TGPMN was rapidly eliminated, and not measurable beyond day 22 after discontinuation, whereas DNA-TGMNC was slowly eliminated, and five patients demonstrated a measurable DNA-TGMNC more than 365 days after therapy discontinuation.Conclusion: Fluctuations in DNA-TGTotal are predominantly caused by corresponding fluctuations in DNA-TGPMN, thus DNA-TGTotal measures recent TGN incorporation in these short-lived cells. Measurement of DNA-TGTotal at 2-4 weeks intervals provides a reliable profile of DNA-TG levels. [ABSTRACT FROM AUTHOR]

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI ( p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture. [ABSTRACT FROM AUTHOR]