BackgroundThe use of intrathecal (IT) methotrexate (MTX) in combination with systemic high dose MTX (HDMTX) is an established procedure for CNS prophylaxis in patients with acute lymphoblastic leukaemia (ALL), but the evidence for the necessity of this combination is not conclusive. An MTX concentration of 1 μM is assumed to be the lowest concentration for an antileukaemic effect.PurposeTo determine the rate of sufficient CSF MTX concentrations (1 μM) in paediatric patients with ALL who received HDMTX, to evaluate the suitability of IT MTX and to correlate MTX plasma and CSF concentrations.Material and methodsA retrospective observational study was conducted between April 2015 and September 2016. We included children up to 18 years with ALL who received 5000 mg/m² over 24 hours in accordance with LAL-SEHOP-PETHEMA-2013 protocols. CSF samples were obtained 18 hours (16–20 hours) after starting the HDMTX infusion and immediately before IT administration of MTX. Plasma samples were obtained at 2, 12, 23, 36, 42 and 60 hours after the start of infusion. CFS samples and plasma MTX at 12 hours were correlated by Spearman’s correlation. MTX was measured by architect chemiluminescence immunoassay.1 ResultsWe included 12 children, aged 2–16 years (7±3.6) who received 36 cycles of MTX. Patients received 5000 mg/m² over 24 hours; one child received 3000 mg/m² was included. MTX plasma levels at 12 hours and CSF concentrations were highly variable, ranging from 48.8 to 179.0 μM (median 72.2μM) and from 0.85 to 2.9 μM (median 1.4 μM), respectively. An MTX concentration above 1μM was found in 33 of 36 CSF samples (91.7%). The patient who received 3000 mg/m² (2 cycles) showed a lower CSF MTX concentration (0.83 and 1.08μM), corresponding to a lower plasma MTX concentration (54.37 and 60.88 μM). The correlation between plasma levels at 12 hours and CSF MTX concentrations was moderate–high (Spearman rank order correlation, r=0.71; p<0.01).ConclusionA potentially antileukaemic MTX concentration of 1 μM was obtained in CSF during the majority of MTX infusions (5000 mg/m2 over 24 hours).References and/or acknowledgements1. Montejano-Hervás P, et al. PKP-034. Determination of methotrexate in CSF by chemiluminescence using the architect. Eur J Hosp Pharm2016;23:A193–4.No conflict of interest
4149 INTRODUCTION: Serum ferritin is an iron overload marker and an acute phase reactant. It has been reported that ferritin levels >1000 or 1500 ng/ml pre-Hematopoietic Stem Cell Transplantation (HSCT) are associated with higher rates of Transplant Related Mortality (TRM), mucositis, Graft versus Host Disease (GVHD) and infections. METHODS: We have retrospectively analyzed the pre-transplant serum ferritin levels in 300 consecutive patients undergone HSCT in our Hospital from January 2005 to June 2012. Patients were classified according to serum ferritin (< and >700 ng/ml, < and >1000 ng/ml, < and >1500 ng/ml) and we have analyzed: overall survival, acute and chronic GVHD, infections (bacterial, fungal and cytomegalovirus), mucositis, interstitial pneumonitis, hepatic veno-oclussive disease, relapse, TRM-100 days and TRM-1 year. Statistical analysis was performed using the SPSS 17.1 programe. We used Kaplan-Meier, LogRank, T- student and Chi-square tests. RESULTS: In our series 152 patients (51%) were undergoing autologous HSCT and 148 (49%) were undergoing allogeneic HSCT (21% Reduced Intensity Conditioning regimen). The median follow up was 15 months, and the overall survival was 59 ± 4% at 5 years (autologous 57 ± 7% and allogeneic 60 ± 5%). TRM-100 days was 1.97% (3 patients) in the autologous group and 8.78% (13 patients) in the allogeneic group. TRM-1 year was 2.63% (4 patients) and 17.56% (26 patients) in the autologous and allogeneic group respectively. In the allogeneic group TRM-1 year was due to GVHD (10.1%), infection (5.4%) and others (2%). Serum ferritin mean pre-HSCT in the global series was 1095 ng/ml (range: 6–11203): autologous 713 ng/ml (range: 8–7120) and allogeneic 1487 ng/ml (range: 6–11203). Serum ferritin was >700 ng/ml in 49% (147 patients), (18% autologous and 31% allogeneic) and <700 ng/ml in 51% (autologous: 32% and allogeneic: 19%). Serum ferritin >700 ng/ml was correlated with worse outcome in survival (50% ± 5% vs 67 ± 6%; p=0.001), and higher TRM-1year (>700 ng/ml 8% vs <700 ng/ml 1.9%; p=0.043). Neither TRM-100 days nor probability of relapse were higher in patients with > 700 ng/ml. In patients with ferritin levels pre-HSCT >700 ng/ml we observed more incidence of infections (bacteremia: p=0.001, autologous and allogeneic), fungal infections (p=0.001 in allogeneic) and Cytomegalovirus infection (p=0.03 in allogeneic). Serum ferritin levels >700 ng/ml were associated with higher incidence of aGVHD grade III-IV (p=0.002), mainly intestinal aGHVD (p=0.014) but we did not find higher incidence of chronic GVHD in the allogeneic group. We found no statistical differences in the incidence of mucositis, interstitial pneumonitis and hepatic veno-oclussive disease between patients with serum ferritin levels > or <700 ng/ml in the global series. Similar results to those of serum ferritin levels >700 ng/ml were obtained when we analyzed ferritin levels >1000 and >1500 ng/ml except for higher incidence rate of chronic GVHD with ferritin >1000 and 1500 ng/ml in the allogeneic group. CONCLUSIONS: The cut-off of serum ferritin > 700 ng/ml pre-HSCT is correlated with worse outcome after transplantation with higher TRM-1 year due to higher incidence of infections and aGVHD. Further studies about the possible benefit of iron chelation therapy pre-HSCT are necessary. Disclosures: No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.