An evidence-based, risk-adapted algorithm for antifungal prophylaxis reduces risk for invasive mold infections in children with hematologic malignancies.

BACKGROUND: Children with hematologic malignancies, especially those who receive intensive chemotherapy, are at high risk for invasive mold infections (IMI) that confer substantial mortality. Randomized controlled trials support the use of antifungal prophylaxis with antimold activity as an optimal strategy for risk reduction in this population, but studies outlining the practical application of evidence-based recommendations are lacking. PROCEDURE: We conducted a 15-year, single-institution retrospective review in a diverse cohort of children with hematologic malignancies treated with chemotherapy to determine the incidence of proven or probable IMI diagnosed between 2006 and 2020. Multivariable logistic regression was used to identify host and disease factors associated with IMI risk. We then compared the incidence and type of IMI and related factors before and after 2016 implementation of an evidence-based, risk-adapted antifungal prophylaxis algorithm that broadened coverage to include molds in patients at highest risk for IMI. RESULTS: We identified 61 cases of proven or probable IMI in 1456 patients diagnosed with hematologic malignancies during the study period (4.2%). Implementation of an antifungal prophylaxis algorithm reduced the IMI incidence in this population from 4.8% to 2.9%. Both Hispanic ethnicity and cancer diagnosis prior to 2016 were associated with risk for IMI. CONCLUSION: An evidence-based, risk-adapted approach to antifungal prophylaxis for children with hematologic malignancies is an effective strategy to reduce incidence of IMI.

Response to Denosumab in 2 Children With Recurrent Giant Cell Tumor of the Bone With Pulmonary Metastasis.

Giant cell tumor of the bone (GCTB) is an uncommon bone tumor, usually localized, and rarely presents at <20 years of age. Denosumab, a fully human monoclonal antibody against RANKL (receptor activator of nuclear factor κB ligand), is approved for the treatment of unresectable GCTB in skeletally mature individuals. We present a case series of 2 pediatric patients with recurrent GCTB with pulmonary metastasis, with clinical response to denosumab therapy.

Blood product administration during high risk neuroblastoma therapy.

The increasing intensity of high-risk neuroblastoma (HR NB) treatment over the last decades has resulted in improved survival at the expense of prolonging therapy and exposure to additional potentially toxic agents. Anemia and thrombocytopenia requiring transfusion are common during therapy for HR NB. Risks of cumulative red blood cell and platelet transfusions are incompletely defined in pediatric oncology patients, however, risks of transfusional iron overload are well described in other populations. This study aimed to determine the number of packed red blood cell (pRBC) and platelet transfusions throughout treatment for HR NB and how these numbers have changed with modern therapy. We performed a retrospective review of 92 patients with HR NB from June 2002 until September 2017. Patients received a median of 20 pRBC and 32 platelet transfusions. Our results demonstrated large numbers of transfusions with significantly increased blood product exposures among patients who received intensified therapy, either with additional induction chemotherapy, tandem autologous stem cell transplants, or dinutuximab plus cytokines with isotretinoin. Similar volumes of pRBC transfusions have been associated with iron overload in other populations and warrant further discussion of guidelines for long-term follow up of HR NB patients.

Congenital spindle cell rhabdomyosarcoma.

Spindle cell and sclerosing rhabdomyosarcoma (ssRMS) is a rare variant of rhabdomyosarcoma, which includes three distinct subtypes. In infants, these tumors are commonly associated with recurring fusions involving VGLL2 or NCOA2 and have a favorable prognosis. We present four cases of ssRMS and 16 additional cases from the literature, which show that these patients present with localized disease and have an excellent prognosis regardless of surgical margin or lack of radiation therapy. Molecularly defined spindle cell rhabdomyosarcoma in infants is likely a biologically distinct entity which may not require the aggressive multimodal treatment used for other subtypes of rhabdomyosarcoma.

Nephrotic-range proteinuria in a child with retinoic acid syndrome.

BACKGROUND: All-trans retinoic acid (ATRA) is a vitamin A derivative that is used in combination with chemotherapy to treat acute promyelocytic leukemia (APL). A serious complication of ATRA is retinoic acid syndrome (RAS), which is characterized by an inflammatory reaction with capillary leakage and myeloid cell tissue invasion that presents with cardiopulmonary symptoms and occasionally acute kidney injury. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old child with APL who developed transient nephrotic-range proteinuria (max urine protein:creatinine ratio 8.6) during two episodes of RAS while on ATRA therapy. ATRA was temporarily discontinued and the patient was treated with a 3-day course of dexamethasone during each episode. He maintained normal renal function throughout and the proteinuria completely resolved. CONCLUSIONS: This is the first reported occurrence of nephrotic-range proteinuria in a child treated with ATRA. Nephrologists should be aware that RAS is a serious complication of ATRA that may lead to proteinuria.