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Iron chelation treatment with deferasirox prior to high-dose chemotherapy and autologous stem cell transplantation may reduce the risk of hepatic veno-occlusive disease in children with high-risk solid tumors.
Chueh, HW, Sung, KW, Lee, SH, Yoo, KH, Koo, HH, Kim, JY, Cho, EJ
Pediatric blood & cancer. 2012;(3):441-7
Abstract
BACKGROUND We evaluated whether iron chelation treatment during induction chemotherapy could safely reduce serum iron levels and thereby reduce the frequency of hepatic veno-occlusive disease (VOD) during high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in children with high-risk solid tumors. PROCEDURE Children diagnosed with high-risk solid tumors between August 2008 and July 2009 were enrolled. Deferasirox treatment (25 mg/kg/day) was initiated when serum ferritin levels increased to more than 1,000 ng/ml during induction chemotherapy. Patients who were diagnosed with the same disease between April 2005 and June 2007 and treated in the same way without any iron chelation treatment formed the control group. Efficacy and toxicity of deferasirox treatment were compared between the two groups. RESULTS Eighteen of 20 patients enrolled received deferasirox treatment. Deferasirox treatment was completed as scheduled in 11 (61.1%) of them without dose reduction or discontinuation. The serum ferritin levels prior to HDCT/autoSCT were lower in the deferasirox group than in the control group (median 1,268 ng/ml vs. 1,828 ng/ml, P < 0.001), although there was no difference in the RBC transfusion amount between the two groups. While 7 (17.9%) VODs developed during 39 HDCT/autoSCTs in the control group, there was no VOD during 40 HDCT/autoSCTs in the deferasirox group (P = 0.005). However, renal dysfunction (38.9%) including Fanconi syndrome (16.7%) was a frequently observed adverse effect of deferasirox treatment. CONCLUSIONS Deferasirox treatment during induction chemotherapy reduces the frequency of VOD during HDCT/autoSCT. The development of renal dysfunction should be closely monitored during deferasirox treatment.
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Validation of brain tumour imaging with p-[123I]iodo-L-phenylalanine and SPECT.
Hellwig, D, Ketter, R, Romeike, BF, Sell, N, Schaefer, A, Moringlane, JR, Kirsch, CM, Samnick, S
European journal of nuclear medicine and molecular imaging. 2005;(9):1041-9
Abstract
PURPOSE The aims of this prospective study were to validate single-photon emission computed tomography (SPECT) with p-[(123)I]iodo-L-phenylalanine (IPA) in brain tumours and to evaluate its potential for the characterisation of indeterminate brain lesions. METHODS In 45 patients with indeterminate brain lesions or suspected progression of glioma, amino acid uptake was studied using IPA-SPECT and compared with the final diagnosis established by biopsy or serial imaging. After image fusion of IPA-SPECT and magnetic resonance imaging, the presence of tumour was visually determined by two independent observers. IPA uptake was quantified as the ratio between maximum uptake in the suspicious lesion and mean uptake in unaffected brain. RESULTS Primary brain tumours were present in 35 cases (12 low-grade and 23 high-grade gliomas). Non-neoplastic brain lesions were confirmed in seven cases (three dysplasias, three inflammatory lesions, one lesion after effective therapy). Visual analysis showed a high concordance between the two observers (kappa=0.90, p<0.001), with sensitivity and specificity of 86% and 100% for the discrimination of primary brain tumours and non-neoplastic lesions. At 30 min p.i., IPA uptake in primary brain tumours was higher than that in non-neoplastic lesions (1.70+/-0.36 vs 1.14+/-0.18, p<0.05). Brain metastases showed no increased uptake (1.13+/-0.22, n=3). The persistent retention of IPA in low-grade gliomas without disruption of the blood-brain barrier was visualised up to 24 h p.i. Low-grade and high-grade gliomas showed equivalent IPA uptake (1.72+/-0.37 vs 1.67+/-0.36 at 30 min, p=0.745). CONCLUSION IPA shows long and specific retention in gliomas. IPA is a promising and safe radiopharmaceutical for the visualisation of gliomas and the characterisation of indeterminate brain lesions.
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Metabolic differences between primary and recurrent human brain tumors: a 1H NMR spectroscopic investigation.
Lehnhardt, FG, Bock, C, Röhn, G, Ernestus, RI, Hoehn, M
NMR in biomedicine. 2005;(6):371-82
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Abstract
High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p = 0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p = 0.0001) and glutamate (Glu)/glutamine (Gln) (p = 0.004). Meningiomas showed increased Ala (p = 0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p = 0.001) relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p = 0.029; tCho, p = 0.034; Glu, p = 0.015; tCho/tCr, p = 0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p = 0.037) and Glu (p = 0.003) and metabolite ratio tCho/tCr (p = 0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n = 11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating characteristics of brain tumor metabolism.