ABSTRACT
Malignant rhabdoid tumor (MRT) of the kidney is a rare pediatric tumor characterized by its aggressive nature and chemoresistance. Our patient had MRT of the right kidney with tumor thrombus in the renal vein, inferior vena cava, and right atrium. He developed transfusion-resistant hematuria. This was successfully controlled with right renal artery embolization allowing completion of his neoadjuvant chemotherapy. He then underwent complete resection of the tumor and thrombus avoiding cardiopulmonary bypass.
Subject(s)
Embolization, Therapeutic , Hematuria/therapy , Kidney Neoplasms/drug therapy , Renal Artery , Rhabdoid Tumor/drug therapy , Chemotherapy, Adjuvant , Child , Hematuria/etiology , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Neoadjuvant Therapy , Nephrectomy , Rhabdoid Tumor/pathology , Rhabdoid Tumor/surgeryABSTRACT
PURPOSE: To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. EXPERIMENTAL DESIGN: Patients received 7 days of fenretinide: 2,475 mg/m(2)/d divided TID (<18 years) or 1,800 mg/m(2)/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). RESULTS: Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n = 35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 µmol/L (coefficient of variation 40-56%) at day 7 course 1. Toxicities were mild and reversible. CONCLUSIONS: Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies.
Subject(s)
Antineoplastic Agents/administration & dosage , Fenretinide/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Neuroblastoma/drug therapy , 3-Iodobenzylguanidine/pharmacokinetics , Administration, Oral , Adolescent , Antineoplastic Agents/adverse effects , Antineoplastic Agents/blood , Antineoplastic Agents/pharmacokinetics , Capsules , Child , Child, Preschool , Disease-Free Survival , Female , Fenretinide/adverse effects , Fenretinide/blood , Fenretinide/pharmacokinetics , Humans , Infant , Iodine Radioisotopes , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local/blood , Neuroblastoma/blood , Neuroblastoma/pathology , Radiopharmaceuticals/pharmacokinetics , Survival Rate , Tomography, X-Ray Computed , Young AdultABSTRACT
X-linked inhibitor of apoptosis (XIAP) deficiency, caused by BIRC4 mutations, is described to cause X-linked lymphoproliferative disease (XLP) phenotypes. However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1A mutation), XIAP deficiency was originally observed to be associated with a high incidence of hemophagocytic lymphohistiocytosis (HLH) and a lack of lymphoma, suggesting that classification of XIAP deficiency as a cause of XLP may not be entirely accurate. To further characterize XIAP deficiency, we reviewed our experience with 10 patients from 8 unrelated families with BIRC4 mutations. Nine of 10 patients developed HLH by 8 years of age. Most patients presented in infancy, and recurrent HLH was common. There were no cases of lymphoma. Lymphocyte defects thought to contribute to HLH development in SLAM-Associated Protein deficiency were not observed in XIAP deficiency. We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately classified as X-linked familial hemophagocytic lymphohistiocytosis.
Subject(s)
Genes, X-Linked/genetics , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphoproliferative Disorders/diagnosis , Mutation/genetics , X-Linked Inhibitor of Apoptosis Protein/genetics , Adolescent , Adult , Blotting, Western , Child , Child, Preschool , Diagnosis, Differential , Flow Cytometry , Humans , Infant , Killer Cells, Natural/metabolism , Lymphohistiocytosis, Hemophagocytic/genetics , Lymphohistiocytosis, Hemophagocytic/metabolism , Lymphoproliferative Disorders/genetics , Lymphoproliferative Disorders/metabolism , Polymerase Chain Reaction , Prognosis , Retrospective Studies , T-Lymphocytes/metabolism , Young AdultABSTRACT
We describe a female with a history of autosomal recessive hyper-IgM (HIGM) syndrome along with a history of autoimmune hemolytic anemia and intermittent lymphadenopathy. She subsequently developed neutropenia, lymphocyostosis and mild thrombocytopenia. Flow cytometry of the peripheral blood revealed the presence of a marked predominance of cytotoxic T lymphocytes, shown to be clonal, with concomitant natural killer (NK) antigen expression. She responded to weekly methotrexate therapy.
