Acute polyosteal osteomyelitis in a patient with congenital ichthyosis and acute lymphoblastic leukemia.

Osteomyelitis can develop after bacteremia in children and is a rare complication of chemotherapy for acute lymphoblastic leukemia. A child with congenital ichthyosis, acute lymphoblastic leukemia and multifocal hematogenous osteomyelitis is described herein. A breached skin barrier secondary to ichthyosis during induction chemotherapy, coupled with impaired immunity, likely provided the opportunity for bacterial seeding, leading to an extensive multifocal osteomyelitis.

Eosinophil-associated inflammation and elaboration of eosinophil-derived proteins in 2 children with raccoon roundworm (Baylisascaris procyonis) encephalitis.

OBJECTIVE: Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection. METHODS: Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophil-derived neurotoxin and major basic protein, were assayed in the CSF. RESULTS: Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophil-derived neurotoxin, and major basic protein were markedly elevated over controls. CONCLUSIONS: This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.

Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: report of effective therapy.

Lymphomatoid granulomatosis, a rare condition in children, affects the lungs primarily but may have significant extrapulmonary manifestations, especially in the central nervous system. We report a case of lymphomatoid granulomatosis with onset after the completion of chemotherapy for childhood acute lymphoblastic leukemia. Two months after treatment ended, the 7-year-old girl developed splenomegaly, cervical adenopathy, and bilateral interstitial pulmonary infiltrates. She improved on cefotaxime but experienced a seizure 1 month later. A computed tomography scan of the head was normal, but her pulmonary infiltrates had become nodular. A computed tomography-guided biopsy of 1 of the nodules revealed cellular interstitial pneumonitis. One month later, she had persistent pulmonary infiltrates, marked splenomegaly, and new seizures. Magnetic resonance imaging of the head revealed cerebral nodules. Itraconazole was begun, and the pulmonary infiltrates resolved. Five months after her initial symptoms, she developed tonic pupil and a decreased level of consciousness. Dexamethasone was initiated. Needle biopsies of the brain were carried out, yielding the diagnosis of severe chronic inflammatory changes focally consistent with granuloma. The child redeveloped splenomegaly and fever, and then suffered an acute decompensation with hypoxemia, tachypnea, splenomegaly, and cardiac gallop. Open-lung biopsy revealed lymphomatoid granulomatosis. Lymphoma-directed therapy was initiated, and the patient had complete resolution of pulmonary and cerebral nodules 5 months later. No intrathecal chemotherapy was administered, and radiation therapy was not necessary. Neuropsychological testing obtained after completion of therapy revealed an improvement in attention, coordination, and fine motor speed over time. She is now in good health and attending school.

Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide.

Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.

Central nervous system atypical teratoid tumor/rhabdoid tumor: response to intensive therapy and review of the literature.

Central nervous system atypical teratoid/rhabdoid tumor (ATT/RT) of infancy and childhood is a unique histologic entity with an extremely aggressive natural history. Standard therapy for infant and childhood medulloblastoma, for which this entity is often mistaken, has been ineffective; most children survive less than 12 months after diagnosis. Intensified therapy has been recently used for children with this disease, with promising results [1,2]. We report four cases of ATT/RT in young children; all had subtotal resections and localized disease at diagnosis. One child treated prior to bone marrow transplant availability died of progressive disease 9 months after diagnosis. Another child, treated with high-dose chemotherapy and radiotherapy in preparation for bone marrow transplant, had a recurrence and died 20 months after diagnosis, without undergoing the transplant. Two children received high-dose chemotherapy and autologous bone-marrow transplant and had a good response to treatment; one survived 19 months, the other child is free of disease 46 months from diagnosis. Intensified therapy has altered the natural history of central nervous system ATT/RT.

The use of implantable venous access devices (IVADs) in children with hemophilia.

PURPOSE: Implantable venous access devices (IVADs), either centrally or peripherally implanted, have become increasingly popular in children with hemophilia to assist in the early treatment of bleeding episodes and in the prevention of arthropathy. Their use has been associated with complications including thrombosis, thrombophlebitis, and infection. We attempted to better define whether the benefits associated with IVADs in this population outweight the associated risks. PATIENTS AND METHODS: We studied the medical records of 35 children from the University of Minnesota's Comprehensive Hemophilia Center who received IVADs between 1992 and 1996. RESULTS: There was no bleeding or thrombophlebitis associated with IVADs in our population. One patient required removal of a central IVAD due to thrombosis. The central IVADs were associated with local infection and bacteremia rates of 3% and 33%, respectively. The rates of local infection and bacteremia associated with peripheral IVADs were both 25%. The majority of infections were cleared with antibiotics, and ports remained intact. Both types of IVADs were associated with a high patient/parent satisfaction. CONCLUSION: Despite being associated with a significant incidence of infection, we believe the benefits of IVADs for children with hemophilia and their families outweigh the risks. Possible explanations for the observed infection rates are discussed.

Retinal toxicity associated with cisplatin and etoposide in pediatric patients.

Cisplatin is an effective chemotherapeutic agent used in the treatment of many pediatric solid tumors. Retinal toxicity is a side effect of the drug reported in adults, but is not well described in pediatric patients. We present the cases of two children treated with cisplatin and etoposide who experienced retinal toxicity documented by visual evoked response (VER) and electroretinogram (ERG). significantly, both patients had abnormal renal function. The mechanism of visual toxicity induced by cisplatin is unknown but may result from central nervous system (CNS) accumulation of drug after repeated doses, especially with high-dose platinum (HDP) containing regimens. Because clearance of platinum is related to adequate renal-function, patients with any decrease in glomerular filtration rate (GFR) may have delayed platinum excretion. We propose that the patients at greatest risk of cisplatin-induced toxicity are those pretreated with nephrotoxic therapy or those with impairment of renal function from other causes. These patients should have prospective ophthalmologic evaluation especially when treated with HDP containing regimens.

One course versus two courses of antithymocyte globulin for the treatment of severe aplastic anemia in children.

PURPOSE: The aim of the therapeutic trials was to optimize the treatment of severe aplastic anemia (SAA) and moderate aplastic anemia in children who lack a suitable bone marrow donor, using immunosuppressive therapy in the most effective combination and dose. PATIENTS AND METHODS: Two sequential therapeutic trials for the treatment of severe and moderate aplastic anemia in children were conducted by 10 institutions. The treatment protocols included antithymocyte globulin (ATG), prednisone, and cyclosporine A (CSA); patients entered on the first protocol, 0190 (ATG X 2), were given two courses of ATG, and those enrolled on the second protocol, 0190B (ATG X 1), were given only one course of ATG. Ten patients were evaluable on ATG X 2. All patients had SAA; three had hepatitis-induced severe aplastic anemia (HI-SAA). Twelve patients were evaluable on ATG X 1; all had SAA, one of whom had HI-SAA. RESULTS: Seven of 10 patients on ATG X 2 responded, and eight of 12 patients treated on ATG X 1 responded. CONCLUSION: Treatment with immunosuppressive therapy using ATG, CSA, and prednisone was very well tolerated. The response rates in both protocols were similar, and results compare favorably with those of previous therapeutic trials, suggesting that a second course of ATG is not necessary.

Serologic evidence that factor IX inhibitor in the plasma of hemophilia B patients detects factor IX on normal red cells.

BACKGROUND: Patients with hemophilia B lack factor IX (F IX). These patients may become alloimmunized after the transfusion of F IX concentrates and may develop F IX inhibitors, which have been characterized as polyclonal IgG4 alloantibodies. Two cases in which F IX inhibitors caused difficulty in compatibility testing and antibody identification were encountered. It was hypothesized that, because F IX is present in normal plasma, it might be adsorbed by red cells in vivo and then be detected during antibody screening tests with serum containing F IX inhibitors. CASE REPORT: Sera from two African American half-brothers with hemophilia B were incompatible with all common and rare red cell phenotypes tested in the anti-human globulin test, but did not react with each other's red cells. The brothers' red cell antibodies were neutralized with both normal plasma and a commercially available F IX concentrate, which indicated that the red cell incompatibility was most probably caused by their F IX inhibitors. Red cells from an unrelated patient with hemophilia B and a very low titer of F IX inhibitor were tested against the half-brothers' sera and did not react. The compatible red cells from one of the half-brothers and the unrelated patient with hemophilia B adsorbed F IX from normal plasma or F IX concentrate after 37 degrees C incubation; this rendered them incompatible with the plasma containing F IX inhibitor from the other half-brother. CONCLUSION: F IX appears to be present on normal red cells and may be detected during compatibility and antibody identification procedures when serum or plasma containing F IX inhibitors is tested.

Follicular large cell lymphoma of the testis in a child.

BACKGROUND: A unique case of primary testicular lymphoma in a child is reported. METHODS: Tumor tissue was studied using immunohistochemical techniques and southern blot hybridization to detect immunoglobulin and bcl-2 gene rearrangement and in situ hybridization for the Epstein-Barr virus (EBV) genome. RESULTS: Light microscopy revealed a lymphocytic infiltrate with a follicular pattern. Immunohistochemical staining revealed lambda light chain restriction and gene rearrangement studies revealed a clonal rearrangement of the immunoglobulin heavy chain, confirming a clonal neoplastic process. Immunostaining failed to detect bcl-2 protein expression, and no evidence of bcl-2 gene rearrangement was noted on southern blot analysis. In situ hybridization for EBV nucleic acid in tumor tissue was negative. CONCLUSIONS: To the authors' knowledge, this is the first report of a case of a primary testicular lymphoma with follicular histology in a child. Despite the follicular histology, no evidence of bcl-2 expression or gene rearrangement was detected.

Use of intracavitary cisplatin for the treatment of childhood solid tumors in the chest or abdominal cavity.

PURPOSE: Intracavitary (IC) delivery of cisplatin (CDDP) has been used in the treatment of a variety of adult malignancies based on the favorable pharmacokinetics obtained locally. Since IC CDDP has not been reported in children, we studied its use in a group of pediatric patients with regard to safety, toxicity, pharmacokinetics, and responses. PATIENTS AND METHODS: Eleven patients with an age range of 8 months to 21 years with diagnoses of rhabdomyosarcoma (n = 5), pleuropulmonary blastoma (n = 2), osteosarcoma (n = 2), Ewing's sarcoma (n = 1), and malignant rhabdoid tumor of the kidney (n = 1) were studied. Eight patients received intrapleural (IPL) CDDP and three received intraperitoneal (IP) CDDP, either at diagnosis (n = 3) or relapse (n = 8), for malignant pleural effusion (n = 3), malignant ascites (n = 2), pleural-based tumor (n = 4), pulmonary metastases (n = 1), or abdominal tumor spillage (n = 1). RESULTS: IC CDDP was well tolerated by pediatric patients. Two patients experienced a transient increase in serum creatinine levels (> two times baseline) and two patients experienced severe neutropenia (absolute neutrophil count < 500/microL). Pharmacokinectic measurements showed a 40-fold advantage for the pleural cavity versus serum after IPL CDDP and serum levels comparable to those achieved with systemic administration of CDDP. Four of five patients who received IC CDDP for malignant ascites or pleural effusion had at least a temporary response. Only three of 11 patients studied had local recurrences following IC CDDP. There are currently four survivors in the study group, including two long-term survivors at greater than 8 years since IPL CDDP treatment. CONCLUSION: The safety, toxicity, and pharmacokinetics of IC CDDP in pediatric patients are similar to that reported in adult patients. The low incidence of local recurrence following IC CDDP in this group of largely relapsed patients suggests that further study of IC CDDP for pediatric patients is warranted.

Expression of somatostatin receptors in childhood neuroblastoma.

Somatostatin receptors are expressed on certain neural crest-derived tumors, including pancreatic islet cell and carcinoid tumors, medullary thyroid carcinomas, pheochromocytomas, and paragangliomas. The authors evaluated the expression of high affinity somatostatin receptors in childhood neuroblastoma using autoradiography techniques with the somatostatin analogue 125I-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28 as the radioligand. Thirty tumors from 30 children with neuroblastoma were analyzed. Twenty-three of 30 tumors that were tested expressed somatostatin receptors. Correlation of somatostatin receptor expression with survival was statistically significant. The survival of those patients whose tumors expressed somatostatin receptors was of longer duration than that of patients whose tumors did not. This was an independent prognostic factor. Somatostatin receptors were expressed more frequently in tumor tissue from patients with lower stages of disease and in those with no evidence of N-myc amplification. Tumoral somatostatin receptors are expressed in a subgroup of patients with childhood neuroblastoma. Survival analysis in this group of patients indicates that somatostatin receptor expression is a favorable prognostic factor. This finding may have important implications for the therapy of children with this malignancy.

Excessive spinal cord toxicity from intensive central nervous system-directed therapies.

BACKGROUND: Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty-three cases of myelopathy that occurred in patients who received intensive CNS-directed therapy were evaluated to identify the determinants of this severe CNS toxicity. METHODS: Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS-directed therapies, including intrathecal cytosine arabinoside (ara-C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara-C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. RESULTS: Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara-C before toxicity occurred; other received intrathecal ara-C and varying combinations of intrathecal MTX, HD ara-C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy-proven cord necrosis; 3 were ventilator-dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. CONCLUSION: Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara-C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara-C and systemic HD ara-C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara-C does not protect against myelopathy. Multiple, frequently spaced courses of CNS-directed therapies must be avoided, especially in patients who have received prior CNS radiation.

A complete ileo-tumor-colic fistula in a child with Burkitt's lymphoma.

A boy with abdominal Burkitt's lymphoma developed rectal bleeding, abdominal distension, pain, and fever three weeks after diagnosis. Imaging studies revealed a necrotic tumor mass allowing a fistulous pathway from the ileum to the proximal colon. A laparotomy was performed, with resection of the large necrotic tumor. The child recovered, and has had no further evidence of Burkitt's disease. The radiological evaluation performed in this case ensured proper medical management and surgical intervention during a life-threatening event. The possibility of bowel perforation as a complication of therapy for abdominal lymphoma must be recognized.

Wilms' tumor: a new cause for urinary extravasation.

We report a case of Wilms' tumor associated with urinary extravasation due to tumor invasion through the renal pelvis and anterior renal capsule. Extravasation of urine exposed to tumor may lead to upstaging of the tumor and the requirement for more intensive therapy.

Carcinoid tumor of the appendix in the first two decades of life.

Carcinoid tumor of the appendix is the most common neoplasm of the gastrointestinal tract in childhood and adolescence. Sufficient long-term follow-up data after surgical treatment are not currently available for patients diagnosed during the first two decades of life. From 1936 to 1988, 23 patients were observed at this institution with histologically confirmed carcinoid tumors involving the vermiform appendix. In contrast to the adult experience, in which the tumor is most commonly encountered as the result of an incidental appendectomy, 18 of these patients presented with signs and symptoms of an acute abdomen directing the surgeon to the appendix. In the other five cases, surgery was performed for other reasons. Median age at presentation was 13.0 years (range, 6 to 20 years). Fourteen patients were female, nine were male. Simple appendectomy was the initial procedure for all patients. Tumor size ranged from "microscopic" to 2.5 cm in largest dimension. Three patients subsequently underwent right hemicolectomy, and one patient had removal of a residual appendiceal stump, but no residual or metastatic tumor tissue was found in any of the resected specimens. Nineteen patients underwent simple appendectomy alone. Eighteen available specimens were reviewed at the time of this study for confirmation of histology and degree of invasion. The tumor invaded to the serosa in nine of 23 (39%). The mesoappendix or periappendiceal fat was involved in seven of 23 (30%). Vessel invasion was not noted in any specimen. Our median follow-up time was very long, being 26 years (range, 9 months to 51 years). No patient has had evidence of recurrent or metastatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)