Background Bone marrow aspirations and biopsies are standard staging procedures for neuroblastoma because the tumor frequently metastasizes to the bone marrow. The presence of bone marrow metastases indicates stage 4 or 4S neuroblastoma by International Neuroblastoma Staging System (INSS) criteria; these stages are also associated with other metastatic sites of disease. We questioned whether bone marrow studies changed the staging or treatment of children with localized, completely resected tumors if there was no other evidence of metastatic spread. If stage of disease rarely changed with bone marrow results, it might be possible to avoid this procedure in a subset of patients with neuroblastoma.Procedure. The staging studies of patients with I NSS stage 1 (n = 29), 4 (n = 60), and 4S (n = 13) neuroblastoma from two institutions were reviewed.Results. There were no patients upstaged from stage 1 to 4 or 4S by bone marrow metastases alone. Fifty-nine of 60 stage 4 patients had other sites of metastases on imaging studies, the remaining patient had an unresectable primary tumor and marrow disease. All subjects with stage 4S disease had liver metastases.Conclusions. Bone marrow studies did not contribute data that changed the stage of patients who had surgically resectable tumors and no evidence of metastatic spread on imaging studies. When present, metastatic spread to the marrow was associated with advanced local tumors or other sites of metastatic disease. Given the relatively small size of our study population, further studies are warranted that investigate the utility of hone marrow studies for patients who otherwise have INSS stage 1 neuroblastoma.

Vigorous host immune reactivity to neuroblastoma may correlate with better prognosis, but identification of human cytotoxic T-lymphocyte (CTL) responses has been relatively unsuccessful. We generated neuroblastoma-reactive CTL lines from two human leukocyte antigen (HLA) A2(+) neuroblastoma patients by stimulation of peripheral blood lymphocytes (PBLs) with irradiated autologous tumor cells pretreated with interferon-gamma in the presence of low concentrations of interleukin-2 (5 U/mL). These lines lyse autologous tumor cells but do not kill HLA mismatched allogeneic tumor cells, Epstein-Barr virus-transformed autologous B cells, or standard natural killer cell targets. Cytotoxic T lymphocytes generated from one patient recognize tumor cells from several HLA-A2 matched children, although the other patient's CTLs do not kill tumor cells from other HLA-A2(+) individuals. Pretreatment of CTLs or target cells with appropriate standard monoclonal antibodies demonstrates that these CTLs are major histocompatibility complex class I (HLA-A2) restricted and that the effector cell population is CD8(+). Our findings suggest that these tumor cells express at least one common HLA-A2 restricted antigen and at least one unique private epitope. Autologous tumor-specific CTLs can be readily generated front patients' PBLs and maintained in long-term culture using standard techniques.

The monoclonal antibody 5.1 H11 recognizes an antigen on human fetal muscle and on rhabdomyosarcoma cell lines and xenografts that has been shown to be homologous to the neural cell adhesion molecule. To evaluate its range of expression, we used immunoperoxidase staining of fresh frozen-tissue sections to determine monoclonal antibody 5.1 H11 reactivity in normal and neoplastic tissue. Among normal tissue specimens, intense antibody staining was seen in brain and peripheral nerve, and weaker staining in ganglionic elements of colon. In addition to 26 of 29 rhabdomyosarcoma specimens, 5.1 H11 antibody showed reactivity to 9 of 10 Wilms' tumors, 6 of 6 neural tumors, and 4 of 4 gliomas, and with single specimens of ectomesenchymoma, clear-cell sarcoma of kidney, undifferentiated sarcoma of liver, ovarian fibroma, and neurofibroma. We conclude that the monoclonal antibody 5.1 H11 recognizes an antigen present not only on fetal muscle but on normal brain and nerve as well. In addition to rhabdomyosarcoma, a variety of other tumors, most of which have been previously shown to express neural cell adhesion molecule, also appear to express the antigen recognized by 5.1 H11. Our results thus offer additional confirmatory evidence that an epitope of neural cell adhesion molecule is the antigen for 5.1 H11.

Aggressive therapeutic maneuvers to reduce the risk for acute renal failure are routine in the management of children receiving therapy for advanced stage Burkitt lymphoma and B cell acute lymphoblastic leukemia. The case histories of 40 children entered into a prospective treatment protocol for high-risk disease revealed that ten of 40 patients (25%) had acute renal failure, two at the time of hospital admission and eight in whom renal insufficiency developed 12 to 132 hours following initiation of cytotoxic chemotherapy. Admission values for serum lactic dehydrogenase and serum uric acid were not statistically different between patients with and without subsequent renal failure. Urine output in the 12 hours prior to antineoplastic therapy was 2.9 +/- 0.8 mL/kg/h in the eight children in whom renal failure developed and 5.3 +/- 0.4 mL/kg/h in the patients who did not (P less than .01). The urinary flow rate in the 24 hours following initiation of chemotherapy was significantly lower in children in whom renal impairment developed (1.0 +/- 0.2 mL/kg/h, mean +/- SE) compared with those who did not (3.7 +/- 0.3 mL/kg/h, P less than .001). Renal failure could not be attributed to hyperuricemia or hyperphosphatemia in the majority of patients with renal failure. One to four hemodialysis treatments (2.5 +/- 0.3) were required for the ten patients. Serum creatinine concentrations returned to normal in the nine survivors. Response to initial antineoplastic therapy was not affected by the presence of renal failure. Renal failure continues to be a major clinical problem in children with Burkitt lymphoma and B cell lymphoblastic leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Despite the clinical experience with Ommaya reservoir-facilitated intraventricular methotrexate (MTX) therapy, established age-related dosage guidelines do not exist. In an attempt to design such a schedule, 49 courses of intra-Ommaya MTX (median dose, 6 mg) administered to 12 patients were studied. Using a fluorescence polarized immunoassay (TDx; Abbott, Dallas, TX), the median peak intraventricular CSF MTX concentration (CSF [MTX]) was 423 mumol/L. Median CSF [MTX] at 24 hours was 4.6 mumol/L, and at 48 hours was 1.05 mumol/L. Median MTX half-life (t1/2) was 5.7 hours. A CSF [MTX] greater than 1 mumol/L was maintained for 24 hours in all but one course and for 48 hours in half of the courses. No correlations were found between MTX dose, patient age, [MTX], t1/2 or prior therapy. Considerable intra- and interpatient variability was seen in MTX disposition, emphasizing the need to monitor [MTX] with each course. A schedule for intraventricular MTX with an initial dose of 6 mg and supplemental doses of 6, 4, or 2 mg at 24 and 48 hours according to serial measurements of intraventricular [MTX] should be initiated to provide a minimum CSF [MTX] of 1 mumol/L for 72 hours.