Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years.

OBJECTIVE: Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008. RESULTS: A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI ( P =0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole ( P =0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality ( P =0.006, odds ratio:4.745; 95% CI: 1.573-14.316). CONCLUSION: Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.

Ifosfamide-related encephalopathy with severe clinical presentations in children with cancer.

INTRODUCTION: Ifosfamide is an alkylating agent, mostly used against variety of solid tumors in pediatric oncology practice. Although hemorrhagic cystitis is known as a common adverse effect, encephalopathy is the another one that should be kept in mind. It may occur in 2-5% of the children, and manifested by different clinical spectrums such as somnolence, lethargy, irritability, excitement, disorientation, confusion, weakness, hallucinations, seizures, movement disorders, and coma. CASE REPORT: Herein, we present two patients who developed generalized seizure activity and one who developed coma during ifosfamide infusion.Management and outcome: In the first two patients, ifosfamide infusion was discontinued and intravenous diazepam was given. Their seizure stopped in a few minutes and neurological examination was back to normal, and no focal deficits were observed. In the third patient, ifosfamide infusion was discontinued, methylene blue and thiamine were given. After the tenth dose of methylene blue, she became neurologically normal, without any mental and motor deficit. Nevertheless, later she developed febrile neutropenia, septic shock and she died. DISCUSSION: These cases highlight that pediatric oncologists and hematologists should be aware of possibility of severe neurological toxicity after administration of ifosfamide in adolescent patients. Apart from seizure, clinicians should also be prepared to notice drowsiness during ifosfamide infusions in children. Most of the time cessation of ifosfamide and hydration is enough. However, in severe toxicities there is a risk of irreversible neurological damage, and for these patients methylene blue (MB) and thiamine treatment should be kept in mind.

Primary Mold-Active Antifungal Prophylaxis Decreases the Need for Chest Computed Tomography Scans in Patients with Acute Lymphoblastic Leukemia.

Current guidelines recommend computed tomography (cCT) scans of the chest in children with leukemia following 96 h of the onset of idiopathic neutropenia to eliminate pulmonary invasive fungal infections (IFIs). However, cCT exposes some children who are at a very high risk of developing secondary cancers to radiation. We aimed to determine the effect of antifungal prophylaxis (AFP) with voriconazole (VCZ) on the need for cCT scans in children with acute lymphoblastic leukemia (ALL) to eliminate pulmonary IFIs during chemotherapy. We retrospectively screened all patients' data from their electronic charts. Children who were diagnosed as having ALL before February 2013 and did (AFP group) or did not (NoP group) receive AFP were divided into two groups and compared regarding cCT scans and relapse-mortality rates. Ninety-six children were diagnosed before February 2013 and did not receive primary AFP and 146 children were administered VCZ following a diagnosis of ALL. There were no significant demographic differences between the groups. A total of 128 cCTs had been required in 62 children in the NoP group, compared with 64 cCTs in 52 children in the AFP group. The percentage of the patients who had required at least one chest CT scan and the mean number of cCT scans in the NoP group were significantly higher compared with the AFP group. Proven-probable IFIs and relapse-mortality rates were higher in the NoP group compared with the AFP group. Mold-active AFP revealed a significant decrease in the need for cCT scans in children with ALL.

What has changed in the last 25 years in osteosarcoma treatment? A single center experience.

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor in the extremities. The main purpose of this study was to determine clinical features, prognostic factors, and treatment results of patients with osteosarcoma at our center. METHODS: We retrospectively analyzed the medical records of children with osteosarcoma between the years 1994-2020. RESULTS: 79 patients were identified (54.4% male, 45.6% female). The most common primary site was the femur (62%). Twenty-six of them (32.9%) had lung metastasis at diagnosis. The patients were treated between 1995- 2013 according to the Mayo Pilot II Study protocol, while the others were treated with the EURAMOS protocol between the years 2013-2020. Sixty-nine patients underwent limb salvage surgery as a local treatment, whereas seven underwent amputation. The median follow-up time was 53 months (2.5-265 months). The event-free survival (EFS) and overall survival (OS) rates at 5 years were 52.1% and 61.5%. The 5-year EFS and OS rates were 69.4% and 80% in females; 37.1% and 45.5% in males (p=0.008/p=0.001). The 5-year EFS and OS rates of the patients without metastasis were 63.2% and 66.3%; with metastasis 28.8% and 51.8% (p=0.002/p=0.05). For good-responders, the 5-year EFS and OS rates were 80.2% and 89.1%; while for poor-responders, 35% and 46.7% (p=0.001). Mifamurtide was used in addition to chemotherapy as of the year 2016 (n=16). The 5-year EFS and OS rates were 78.8% and 91.7%, respectively for the mifamurtide group; 55.1% and 45.9%, respectively for the non-mifamurtide group (p=0.015, p=0.027). CONCLUSIONS: Metastasis at diagnosis and poor response to preoperative chemotherapy were the most important predictors of survival. Females had a better outcome than males. In our study group, the mifamurtide group`s survival rates were significantly higher. Further large studies are needed to validate the efficacy of mifamurtide.