Background After High-Dose Methotrexate (HD-MTX), folinic acid rescue therapy (Leucovorin) is administered to reduce side effects in pediatric acute lymphoblastic leukemia (ALL) patients.... Show moreBackground After High-Dose Methotrexate (HD-MTX), folinic acid rescue therapy (Leucovorin) is administered to reduce side effects in pediatric acute lymphoblastic leukemia (ALL) patients. Leucovorin and MTX are structural analogues, possibly competing for cellular transport and intracellular metabolism. We hypothesize that Leucovorin accumulates during consecutive courses, which might result in a lower MTX uptake. Methods We prospectively measured red blood cell (RBC) folate and MTX levels during four HD-MTX and Leucovorin courses in 43 patients treated according the DCOG ALL-11 protocol with 2-weekly HD-MTX (5 g/m(2)/dose) and Leucovorin (15 mg/m(2)/dose) using LC-MS/MS. We estimated a linear mixed model to assess the relationship between these variables over time. Results Both RBC MTX-PG and folate levels increased significantly during protocol M. MTX-PG(2-5)levels increased most substantially after the first two HD-MTX courses (until median 113.0 nmol/L, IQR 76.8-165.2) after which levels plateaued during the 3(d)and 4th course (until median 141.3 nmol/L, IQR 100.2-190.2). In parallel, folate levels increased most substantially after the first two HD-MTX courses (until median 401.6 nmol/L, IQR 163.3-594.2) after which levels plateaued during the 3(d)and 4th course (until median 411.5 nmol/L, IQR 240.3-665.6). The ratio folate/MTX-PG decreased significantly over time, which was mostly due to the relatively higher increase (delta) of MTX-PG. Conclusion These results suggest that the increase in RBC folate levels does not seem to have a large effect on RBC MTX levels. Future studies, assessing competition of Leucovorin and MTX on other cellular mechanisms which might negatively affect treatment efficacy, are necessary. Show less
Objective: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1 -> 3)-beta-D-glucan (beta-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV... Show moreObjective: To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1 -> 3)-beta-D-glucan (beta-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients. Methods: HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum beta-D-glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum beta-D-glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. Results: In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum beta-D-glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients beta-D-glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. Conclusions: The level of serum beta-D-glucan-but not AdoMet - was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring. (C) 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved. Show less
OBJECTIVE To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1→3)-β-D-glucan (β-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients.... Show moreOBJECTIVE To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1→3)-β-D-glucan (β-D-glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative patients. METHODS HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum β-D-glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum β-D-glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. RESULTS In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum β-D-glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients β-D-glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. CONCLUSIONS The level of β-D-glucan--but not AdoMet--was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring. Show less
