Iron deficiency is a common cause of anemia (IDA) in infancy and can be associated with neurocognitive impairments. Iron-refractory IDA (IRIDA) has recently been described as an inherited cause of IDA due to loss-of-function mutations in the TMPRSS6 gene. IRIDA is characterized by a lack of response to iron replacement. Here we report a new case of IRIDA with its biological parameters and its functional consequences, including neuropsychological impact. The latter was evaluated by the Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition and subtests. We report a 5-year-old French Canadian boy who was incidentally diagnosed with a severe microcytic anemia at 2 years of age (hemoglobin 52 g/L, mean corpuscular volume 50 fL). Except mild pallor, he was asymptomatic of his anemia. Although he had a slight response to intravenous iron therapy, his hemoglobin remained <92 g/L, with persistent microcytosis, low serum iron, but normal ferritin levels. Blood hepcidin level was higher than those of his parents and control (patient 11.2 nM, father 9.06 nM, mother 4.07 nM). Compound heterozygosity for TMPRSS6 paternally inherited c.1324G>A and maternally inherited c.1807G>C mutations were eventually identified. The patient had normal development and growth. Neuropsychological evaluation revealed excellent performance, with high Wechsler Preschool and Primary Scale of Intelligence–Fourth Edition scores (ie, 82nd percentile for both global intelligence and general ability index). In conclusion, TMPRSS6 c.1807G>C in conjunction with c.1324G>A results in IRIDA. In contrast to the usual form of IDA, IRIDA may not be associated with neuropsychological deficits.
BACKGROUND: Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS: This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. The primary objective for PN was to evaluate the overall response rate based on RECIST 1.1 criteria after daily oral trametinib administration for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS: As of January 1, 2022, 45 patients with PN were enrolled in the study. Twenty-eight completed treatment and were available for analysis. For these patients, the median age was 11.4 years (range 0.7-19.8) including 16 males (57.1%). The majority did not receive prior systemic therapies (71.4%). The median volume of PN at baseline was 49.5 cm3 (range 2.6 to 469). Among the 28 patients, 25 (89.3%) completed 18 cycles as planned. One patient discontinued due to adverse reaction, one patient refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 15.9 months (range 4.6 to 16.8). Median duration of follow-up was 29.7 months (range 17.7 to 38.1). A total of 32 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 24.1%. Volumetric assessment demonstrated an overall response rate of 60.7% and 62.5% of PN showed a decrease of more than 20% in volume. Median decrease in volume was -30% (range -93.5 to 14.3). Twenty-seven patients (93.1%) had durable response without progression (lasting ≥1 year). CONCLUSION: We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib appears effective and offers durable response.
BACKGROUND Plexiform neurofibromas (PN) are observed in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. Patients received daily oral trametinib (MEK inhibitor) for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS As of May 15, 2022, 46 patients with PN were enrolled in the study and the recruitment was completed for this study arm. Thirty-four completed treatment and were available for analysis. For these patients, the median age was 10.5 years (range 0.7-19.8). The median volume of PN at baseline was 51cm3 (range 2.6 to 487.6). Among the 34 patients, 28 (82.4%) completed 18 cycles as planned. Two patients discontinued due to adverse reaction, three patients refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 16.8 months (range 2.8 to 16.8). Median duration of follow-up was 30.4 months (range 8.2 to 42). A total of 38 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 13.1%. Volumetric assessment demonstrated an overall response rate of 64.7% (22/34 patients), and 65.8% (25/38 PN) of PN showed a decrease of more than 20% in volume. Median volume change was -30% (range -93.5 to 14.3). Thirty-one patients (91.1%) had durable response without progression (lasting ≥ 1 year). After discontinuation of treatment, one patient underwent surgery and three patients resumed MEK inhibitor. CONCLUSION We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib is effective and offers durable response.
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