Central nervous system involvement in children with sarcoma.

OBJECTIVES: To summarize and analyze the experience in CNS involvement (CNSI) in children with sarcomas treated in the above-mentioned institutions. PATIENTS AND METHODS: From 1990 to 2001, all medical charts were retrospectively reviewed: 19 sarcoma patients (12 boys and 7 girls) were diagnosed with CNSI (4 osteogenic sarcomas, 11 Ewing sarcomas, 2 rhabdomyosarcomas, 1 alveolar soft part sarcoma and 1 mesenchymal chondrosarcoma). Mean age of all patients at the time of initial diagnosis was 14.9 years (range: 4-24 years), mean age at the time when CNSI was diagnosed was 16.9 years (range: 5.5-27 years). RESULTS: The frequency of CNSI among our patients was 6.17%. The following symptoms and signs (sometimes combined) presented: headache (10 patients), nausea and vomiting (6 patients), seizures (11 patients) and focal neurological signs (9 patients). The mean duration of time elapsed since diagnosis of CNSI till death or last follow-up was 5.2 months (SD: +/-5.7 months). Four patients received chemotherapy (CT) alone, 8 CT and radiotherapy (RT), 2 RT alone, 3 supportive treatment only, 1 CT and surgery and 1 surgery alone. Sixteen patients died; there was no significant difference in the duration of survival between those who were treated with RT or surgery (mean +/- SD: 6.77 +/- 6.56 months) and those who received only CT or supportive treatment (mean +/- SD: 2.60 +/- 2.94 months) (p = 0.07). Brain disease was the main cause of death in all but 1 patient who died 4 days after autologous bone marrow transplantation from uncontrolled sepsis. In 16 patients, CNSI was part of a metastatic disease. CONCLUSIONS: Among children with sarcoma, CNSI is encountered in 6.17% of cases. More effective therapy has to be developed in order to improve their outcome.

Unusual presentation of mastoid eosinophilic granuloma in a young patient.

Eosinophilic granuloma is a well-recognized form of Langerhans cell histiocytosis, most commonly involving the skull bones, usually with an excellent prognosis. Recurrent and difficult to recognize osteolytic lesions of the skull are encountered only rarely. A patient with recurrent eosinophilic granuloma of the skull is reported. In spite of appropriate multimodality treatment, there were several recurrences, most recently with involvement of the mastoid process. Imaging studies revealed extensive involvement of surrounding structures with expansion of the tumor into the middle cranial fossa and slight pressure on the antero-medial portion of the temporal lobe of the brain. Despite extensive involvement, the patient had no complaints. Because of the rarity of such silent and unpredictable lesions, a systematic approach with regular CT and MRI follow-up is suggested.

Detection of isolated distant metastasis in soft tissue sarcoma by fluorodeoxyglucose positron emission tomography: case report.

Fluorodeoxyglucose (FDG), labeled with F-18, is a glucose analog that accumulates in cells in proportion to the rate of glucose metabolism, and increased carbohydrate metabolism has been recognized as a feature of malignant cells versus normal cells. In addition, it permits the detection of metastases not discovered by bone scan. Although detection of the primary site of disease is usually accomplished well with conventional techniques, the performance of FDG positron emission tomography (PET) may be useful to determine metastases that are not clinically evident. The authors describe a case of early detection of distant metastases by FDG-PET in a young patient diagnosed with rhabdomyosarcoma of the hand.

Late recurrence of combined hepatocellular carcinoma and hepatoblastoma in a child: case report and review of the literature.

We report on a case of late relapse of hepatocellular carcinoma in a child suffering from combined hepatoblastoma and hepatocellular carcinoma, stage IV. This is a rare event, as it has been accepted that a 5-year period free of any signs of disease in children suffering from malignant hepatic tumors is sufficient to classify such patients as survivors. In our patient, recurrence of the hepatocellular carcinoma component was diagnosed more than five years after the initial diagnosis. This case illustrates the need for more prolonged follow-ups for such children.

Large cell lymphoma of bone presented by limp.

We present a rare case of anaplastic large cell lymphoma of the bone in the leg of a child. The patient initially presented with suspected osteomyelitis of the fibula and was treated by antibiotics without apparent success. Thereafter, an open biopsy of the lesion was performed and the correct diagnosis was established. This rare case demonstrates the difficulties that a treating physician meets in establishing the correct diagnosis in a child presenting with limping. A review of the pertinent literature is introduced.

Guidelines for the recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer: report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This is the eighth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. It deals with a topic discussed and approved by the SIOP Committee; namely, "Recognition, prevention, and remediation of burnout in health care professionals participating in the care of children with cancer." It is addressed to the Pediatric Oncology community and outlines: 1) the general definition of burnout as mental and physical exhaustion, indifference, sense of failure as a professional, and sense of failure as a person; 2) the causes of burnout from the nature of the work itself, the work environment, and the characteristics of the individual; 3) the prevention of burnout, changing the detrimental aspects of one's work environment and modifying one's own behavior; and accepting methods to remediate burnout when it occurs.

Immune and hematopoietic reconstitution after transplantation of cord blood progenitor cells: case report and review of the literature.

Transplantation using umbilical cord progenitor cells as the source of the stem cells is increasingly recognized as another form of allogeneic transplantation with curative intent. However, the different patterns of hematopoietic and immunological reconstruction have been described in very few patients. A 20-month-old boy presented with acute leukemia. He received standard AML induction and consolidation therapy, after which he underwent allogeneic transplantation using HLA-matched sibling stem cells obtained from the umbilical cord. The preparative regimen consisted of busulfan and cyclophosphamide. White cell recovery, despite concomitant use of G-CSF, was slow, reminiscent of the engraftment pattern without the use of growth factor. Erythroid recovery was best recorded using fetal cell HbF level. Platelet transfusion independence occurred on day +31. Immunologic reconstitution revealed an early NK cell recovery by 6 weeks and progressive T cell recovery until 3 months, with continued increase in counts thereafter. However, the CD4/CD8 ratio remained low even at 14 months post-transplantation. Recovery of B cells was slower until day +120. Proliferative response was within normal range on day +120. This report describes the unique engraftment pattern following umbilical cord blood transplant and emphasizes the pattern of immunological and hematological reconstitution.

Male gonadal function in survivors of childhood Hodgkin and non-Hodgkin lymphoma.

The aim of this study was to investigate the impact of therapy on long-term gonadal function of young people cured of childhood lymphomas and to assess whether a prepubertal state during the treatment protects the gonads from chemotherapy and/or radiotherapy late effects. Clinical evaluation, semen analysis, and endocrine status were studied in 20 survivors of childhood lymphomas. Five patients received Inverted Y radiotherapy, 2320 cGy (1550-4000); all 20 received chemotherapy as follows: MOPP/ABVD protocol, 9 patients; COMP protocol, 5 patients; MOPP protocol, 3 patients; other protocols, 3 patients. Semen analysis results were as follows: normal values, 4/20 patients; oligospermia, 8/20 patients; azoospermia, 8/20 patients; FSH above normal level, 10/20 patients; 4/5 who received Inverted Y irradiation were azoospermic and 1 was severely oligospermic. Treatment damage to the testis involves tubular germinal elements. Radiotherapy and chemotherapy combinations that included nitrogen mustard or cyclophosphamide were associated with high rates of oligospermia and azoospermia. MOPP/ABVD combination did not have a significant better outcome of sperm counts compared to MOPP alone. Age at chemotherapy did not correlate with the sperm count; hence a prepubertal state did not protect the gonad from the late effects of treatment.

Changes in the policies of the department of hematology, 1982-1998, designed to promote the mental health of children with leukemia and enhance their quality of life.

A perceived personal control (PPC) preventive intervention model that had earlier received empirical and theoretical verification was applied to a population of pediatric leukemia patients to promote their mental health and enhance their quality of life. The PPC model entails intervention on two complementary levels. On the personal interaction level, preventive intervention is administered by a network of natural and organized support systems, while the social action level leads to the introduction of changes in policies, structures, allocation of resources, and services. Preventive intervention in both domains is discussed with respect to changes in policies introduced between 1982 and 1998 in the hematology department of Rambam Medical Center in Haifa, Israel, as well as in other relevant departments catering to children with leukemia, to foster the positive mental health of these children.

Pediatric thyroid carcinoma: 22 years of experience at the Northern Israel Oncology Center (1973-1995).

Over the past 22 years, 16 children with thyroid carcinoma were referred to the Northern Israel Oncology Center. All patients had undergone surgical procedures, either total or subtotal thyroidectomy, and 7 patients had undergone cervical lymph node dissections. Postoperatively, 5 patients underwent thyroid ablation with radioactive 131I as first treatment. Two patients received postoperative external radiation therapy to a field encompassing the cervical region, superior mediastinum, and both supraclavicular grooves. After a median follow-up of 60 months (range, 5-169 months), all patients are alive with no evidence of recurrent disease. Two patients who had recurrences, one in the submaxillary lymph nodes and one in the lungs, were salvaged successfully with retreatment with 131I therapy. No severe acute or long-term side effects were exhibited. The long-term results of treatment of pediatric thyroid carcinoma are excellent, but there remains disagreement over the extent of surgical and postsurgical treatment required.

Successful haploidentical bone marrow transplantation in Fanconi anemia.

A 10-year-old girl with Fanconi anemia and severe aplastic anemia underwent a haploidentical BMT from her mother due to lack of a matched family donor. T cell depletion was done by positive selection of CD34 cells with immunomagnetic beads. Due to graft rejection a second haploidentical BMT from the father was successfully undertaken. No immunosuppression was given after the transplant. Immunological reconstitution took approximately 6 months, with no GVHD or severe infections. Such a transplant, containing a large purified CD34 cell fraction with a minimal number of added T cells, should be considered as the treatment of choice for patients with Fanconi anemia if no HLA matched donor is available.

The role of chemotherapy in childhood soft tissue sarcomas other than rhabdomyosarcomas: experience of the Northern Israel Oncology Center.

Forty-three children with nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) were treated at the Northern Israel Oncology Center in Haifa, Israel, from 1971 to 1996. The male:female ratio was 1.5:1 and the median age of patient was 10 years (range, 3 months-18 years). The most common histopathologic diagnoses were fibrosarcoma (32.5%) and synovial sarcoma (16%). The sites of primary tumor were lower limb (35%), trunk (18%), upper limb (16%), head and neck (16%), and retroperitoneum (11%). By Intergroup Rhabdomyosarcoma Study classifications, 13 patients presented as group I, 15 patients as group II, 10 patients as group III, and 5 patients as group IV. Median follow-up time was 63 months (range, 6 months-18 years). The estimated survival after a 5-year period is 72% (SE +/- 17) for patients in group I, 75 +/- 15% in group II, 90 +/- 9% for patients in group III, and 40 +/- 21% for patients in group IV. Eleven patients relapsed; 4/6 who developed local relapse were cured and are alive with disease, while 4/5 who developed distant metastases are dead. For the 28 patients who underwent complete resection at diagnosis, the estimated survival after a 5-year period is 87 +/- 5% vs. 60 +/- 17% for the 15 patients who underwent partial excision or biopsy. Local radiotherapy was delivered after surgery to group III patients. Preoperative and postoperative chemotherapy was delivered to the patients of groups III and IV, and postoperative chemotherapy only to group II patients. Chemotherapy produced demonstrable gain in survival for group II and III patients but not for patients with metastases. The authors conclude that an aggressive surgical approach is needed in patients with NRSTS. Chemotherapy may help as a preoperative treatment in bulky disease or as a postoperative treatment for microscopic residual disease.

Prognostic significance of DNA ploidy in childhood astrocytomas.

The ability to divide subsets of children with astrocytoma into prognostic groups is limited because only a few clinical and pathologic variables are available. This study evaluated DNA ploidy as a potential prognostic factor in 30 children with diagnosed gliomas and examined the correlation of flow cytometric analysis to other parameters such as sex, age at diagnosis, histologic grading, localization of tumor, and completeness of surgical resection. Seventeen children with low-grade glioma and 13 with high-grade glioma were retrospectively reviewed; mean age of the patients was 8.2 years, and mean follow-up of the population was 7.6 years. The tumor was localized to the cerebrum in 19 patients, the cerebellum in 7 patients, the brain stem in 3 patients, and the spine in 1 patient. Fourteen patients underwent complete excision and 16 patients underwent partial excision. DNA diploidy was demonstrated in 21 patients and aneuploidy in 9 patients. Twenty children had no evidence of disease and 10 died of disease. Of the patients with diploid tumors, 81% survived, compared to only 33% survival among patients with aneuploid tumors (p < .011). By Cox regression analysis with age, gender, type of excision, grade, location of tumor, and ploidy as independent variables, ploidy was a statistically significant predictor of survival (p = .043). This investigation provides further evidence that flow cytometry may have prognostic value in children with gliomas. Thus, a larger number of tumors can be studied to extend and validate these observations.

Clinical and radiographic response in three children with recurrent malignant cerebral tumors with high-dose tamoxifen.

The purpose of this study was to deliver tamoxifen as antiangiogenic therapy to children with recurrent progressive malignant brain tumors. Tamoxifen was administered orally in very high dosage to one child as monotherapy and to two children in combination with oral etoposide and dexamethasone. One boy was diagnosed with high-grade astrocytoma in the brain stem, one girl with anaplastic ependymoma of the fourth ventricule, and one girl with high-grade astrocytoma in the midbrain. Conventional treatment with multiple surgeries, first- and second-line chemotherapy, and external beam therapy had failed. Tumor reduction was seen in radiographic images together with clinical improvement in 2 children, and clinical and radiographic halting of tumor progression was demonstrated in the patient with anaplastic ependymoma. None of the patients developed complications from the treatment. Follow up of the patients ranged from 15 to 30 months with a mean of 17 months. These encouraging preliminary results suggest a potential for this type of therapy. More studies are needed to start clinical trials and prove that angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.

Pharmacokinetic analysis of amikacin twice and single daily dosage in immunocompromised pediatric patients.

Ten children received amikacin twice daily and 13 were treated using the single daily protocol. All had fever and neutropenia on admission, and received a total daily dose of 20 mg/kg when included in the study. Individual pharmacokinetic parameters were calculated using a one-compartment model for two blood amikacin samples. The mean (+/- SD) of elimination half-life (h), amikacin clearance (l/h/kg), volume of distribution (l/kg), peak concentration (microgram/ml) and trough concentration (microgram/ml) were: 2.51 (0.74) and 2.85 (0.32) h; 0.26 (0.16) and 0.115 (0.02) l/h/kg; 0.74 (0.44) and 0.47 (0.11) l/kg; 19.1 (12.3) and 42.6 (12.6) micrograms/ml; 0.85 (0.74) and 0.18 (0.24) microgram/ml with twice and single daily dosage schedules, respectively. A single daily dose of amikacin had a significantly longer elimination half-life, lower clearance, higher peak concentration and lower trough concentration in comparison to the twice-daily schedule. The use of amikacin 20 mg/kg daily delivered in a single daily dose is recommended for immunocompromised pediatric patients with fever and neutropenia, in spite of the measured pharmacokinetic differences.