Elevated myelin basic protein levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia.

Cerebrospinal fluid was examined from 70 children with acute lymphoblastic leukemia for evidence of active myelin breakdown based on the release of myelin basic protein (MBP). Fifty-three asymptomatic children were followed from diagnosis with serial MBP determinations. Eight (15.1%) of 53 children had abnormal elevations of MBP, six of eight before receiving presymptomatic central nervous system therapy. Long-term observations are in progress. For comparison, six children with clinical and radiologic findings of leukoencephalopathy had abnormal MBP determinations, whereas no abnormalities were detected in 11 children with meningeal leukemia.

The treatment of Wilms' tumor patients with pulmonary metastases detected only with computed tomography: a report from the National Wilms' Tumor Study.

To evaluate the prognosis of patients with Wilms' tumor who have pulmonary densities identified on a computed tomographic (CT) scan of the chest, but have a negative plain chest radiograph, we reviewed the treatments and outcome of 32 patients randomized or followed on National Wilms' Tumor Study (NWTS)-3. The 4-year event-free and overall survival percentages of 18 of these patients who had a favorable histology tumor and were treated as stage IV tumors with three or four drugs plus whole-lung irradiation were 88.1% and 94.0%, respectively. The 4-year event-free and overall survival percentages for nine favorable histology patients treated less aggressively based on the extent of locoregional disease with two or three drugs and without whole-lung irradiation were 88.9% and 88.0%, respectively. There were no statistically significant differences in the 4-year event-free or overall survival percentages between the two groups. The current data do not demonstrate improved survival for favorable histology patients treated with whole-lung irradiation for pulmonary metastases identified only on chest CT scan. However, due to the small number of patients included, no statistically valid conclusions regarding the roles of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and/or whole-lung irradiation in the treatment of these patients can be drawn from the present analysis. Additional patients need to be systematically studied to determine if these preliminary observations can be confirmed.

Circulating immune complexes in childhood malignancies: a Pediatric Oncology Group study.

Pretreatment serum samples obtained at diagnosis from 89 children with various pediatric malignancies were examined for circulating immune complexes (CIC) using the [125I]Clq binding assay. The study population consisted of 35 children with acute lymphocytic leukemia (ALL), 22 children with acute non-lymphocytic leukemia (ALL), 24 with neuroblastoma (NB), and eight with osteosarcoma (OS). Concomitant quantitation of immunoglobulins was performed in 55 patients, revealing normal values for age. Increased levels of CIC at diagnosis were found in 9%, 22%, 42%, and 50% of children with ALL, AML, NB, and OS, respectively. Except for a higher proportion of CIC-positive patients observed in stage IV NB (nine of 17) compared to stage I-III NB (one of seven), no correlation was observed between initial CIC level and presenting clinical features, response to treatment, prognosis, or presence of infection. Longitudinal sampling of six NB and two OS patients did not reveal a clear relationship between disease activity and quantity of CIC. For the pediatric malignancies studied, these data demonstrate minimal value in quantitating CIC as a means of assessing disease activity or predicting response to treatment and are in contrast to the apparently adverse effect of elevated pretreatment CIC on response to therapy and survival observed in adults with ALL, AML, and OS.

Prognosis for Wilms' tumor patients with nonmetastatic disease at diagnosis--results of the second National Wilms' Tumor Study.

Multivariate statistical methods were used to study prognosis for 632 patients entered on the second National Wilms' Tumor Study who had nonmetastatic, unilateral disease at diagnosis. Separate analyses were conducted for each of four endpoints: abdominal recurrence, distant metastasis, relapse without regard to site, and death. The two most important predictors for metastasis and general relapse were an unfavorable (anaplastic or sarcomatous) histology and the presence of microscopically confirmed disease in the regional lymph nodes. Operative spillage of tumor increased the rates of abdominal recurrence and death, even after accounting for histology and lymph node effects. The presence of a tumor thrombus in the renal vein or IVC increased the risk of metastasis, and intrarenal vascular invasion was associated with general relapse after accounting for histology, lymph nodes, and spillage. However, these latter associations were weaker, and some uncertainty remains regarding the true prognostic import of such findings due to a high degree of collinearity among variables. By contrast to the results of a similar data analysis for the first National Wilms' Tumor Study, specimen weight had no bearing on outcome, and the effects of age at diagnosis were entirely explained by the association of age with other more critical factors.

Immunologic chimerism as evidence of bone marrow graft acceptance in an identical twin with acute lymphocytic leukemia.

Bone marrow from a well child was infused into her identical twin who had acute lymphocytic leukemia. In an attempt to provide an immunologic tag for use in twin transplantation, the donor twin was immunized to Keyhole limpet hemocyanin (KLH) and yellow fever virus prior to the marrow infusion. Subsequent immunological chimerism in the recipient twin gave evidence for graft acceptance.

Peripheral blood T and B cell characteristics in a patient with severe combined immune deficiency (SCID) maintained in a gnotobiotic environment.

Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct immunofluorescence. A receptor for the activated C3 complement component was detected on 27-47 percent of his lymphocytes. Only 4-12 percent of the peripheral blood lymphocytes formed spontaneous rosettes with sheep erythrocytes (E-R). In general, no blastogenesis was detected in lymphocyte cultures stimulated with pokeweed mitogen or phytohemagglutinin although transient slightly positive responses to both mitogens were occasionally observed. Incubation of lymphocytes with bovine thymosin Fraction V did not increase the percentage of E-R nor induce lymphocyte blastogenesis in the presence of phytohemagglutinin.

A longitudinal study of T and B lymphocytes from a three-year-old patient with severe combined immunodeficiency (SCID) in 'gnotobiotic protection'.

Fluctuations in the percentages and absolute numbers of T and B lymphocytes were observed in the peripheral blood of a patient with severe combined immunodeficiency maintained in a gnotobiotic environment. Up to 24 months of age, 72-86% of the lymphocytes had surface membrane immunoglobulin (SMIg), 37-47% bore a receptor for C3(EAC-RFC), and 3-12.5% formed spontaneous rosettes with sheep erythrocytes (E-RFC). These values persisted until 30 months, after which shifts in the percentages and absolute numbers of T and B cells were observed. A significant decrease in the proportion of SMIg-bearing cells to 20-40% (169-405 mm3), and EAC-RFC to 10.5-39% (114-259 mm3), was accompanied by a general increase in the proportion of T cells to 19-60% (141-1026 mm3), representing a lymphoid subpopulation approach to normal levels.

Wilm's Tumor: An Update.

Major advances have been made against Wilms' tumor as a result of treatment methods developed by single institutions that then have been confirmed and extended by national cooperating groups. Better survival rates have been achieved, and therapy has been refined so that treatment can be reduced in early stage disease without jeopardizing tumor control. This results in fewer short- and long-term complications, an especially important consideration in children. Their organs and tissues are vulnerable to anti-mitotic treatments such as chemo- and radiotherapy, that can produce disabling if not lethal dysfunctions. This progress has been the result of the cooperative efforts by multiple specialists, and provides evidence of the value of such integrated studies. They have changed the outlook from a 90% death rate in the early years of this century to the 90% survival rate now possible with modern management.

Degenerative changes in neutrophils: an indicator of bacterial infection.

A review was made of 195 peripheral blood smears of 157 neonates who required sepsis work-up in the first month of life. Degenerative changes of neutrophils including vacuolization and toxic granulation were observed frequently in infants with culture-proven bacterial sepsis. Of 21 peripheral blood smears from 20 neonates subsequently proven to have bacterial infection, 17 had vacuolization present in the neutrophils for a sensitivity of 81%, a specificity of 93%, and a positive predictive accuracy of 59%. Toxic granulation changes in neutrophils showed similar results. This simple test can be performed easily in all hospitals; it does not require special laboratory facilities. The test appears to provide a valuable adjunct in the early detection of neonatal bacterial infection.

Early detection of bacteremia in an outpatient clinic.

A total of 570 patients, aged less than 24 months, who were seen in the emergency room at Texas Children's Hospital for evaluation of acute febrile illness had a WBC count, differential count, and a blood culture obtained. Bacteremia occurred in 7.7% (n = 44) (22 Haemophilus influenzae; 17 Streptococcus pneumoniae; three Escherichia coli; one group B Streptococcus; one Staphylococcus aureus). The sensitivity, specificity, and positive predictive value of morphologic changes (vacuolization and toxic granulation) of polymorphonuclear neutrophils (segmented neutrophils plus band cells), WBC count greater than or equal to 15,000/microL and band cells greater than or equal to 500/microL were examined. Additionally, abnormalities in three of four tests (WBC count greater than or equal to 15,000/microL, band cells greater than or equal to 500/microL, segmented neutrophils greater than or equal to 10,000/microL, and/or total polymorphonuclear neutrophils greater than or equal to 10,500/microL) were evaluated. Morphologic changes of polymorphonuclear neutrophils were noted frequently in patients with culture-proven bacteremia (63% and 51% positive predictive value for vacuolization and toxic granulation, respectively) and were more predictive of bacterial infection than traditional tests. If both vacuolization and toxic granulation were present, the positive predictive value increased to 76%. Examination of the peripheral blood smear may provide important adjunctive information for the presence of bacteremia prior to bacteriologic confirmation.

Head and neck malignancies in children: an age-incidence study.

One hundred forty-seven (147) children under 18 years have been treated for head and neck malignancies at Texas Children's Hospital from 1970 to 1985 and form the data base for this study. In order of frequency, the most common tumors were lymphoma, Langerhans' histiocytosis (LH), rhabdomyosarcoma, neuroblastoma, and other soft-tissue sarcoma. Children under 2 were most likely to have LH; those from 3 to 5, LH or lymphoma; and those over 5, lymphoma.

Bilateral Wilms' tumor.

Recent studies indicate a favorable outcome with bilateral Wilms' tumor. From 1971 to 1985, ten children between the ages of 6 months and 5 years were treated for this disease. During the early part of the series, five patients had nephrectomy on one side and partial nephrectomy on the other side, and one patient had bilateral partial nephrectomies at the same operation. More recently four patients initially had a biopsy of both tumors and lymph node sampling followed by chemotherapy. At the second-look procedure two patients had multiple biopsies because there was no obvious tumor. Histologically there was no tumor on the third-look procedure in these two patients. Nine patients had a favorable histology of the Wilms' tumor. One patient had a favorable histology on one side and an unfavorable type of histology on the other side. Eight patients are surviving between 6 months and 13 years. Two died of extensive disease within 16 months of diagnosis. One patient had an unfavorable histology. The good results following partial nephrectomies have led us to attempt to conserve additional tissue, as has been done in the last four patients. Our early results suggest biopsy of the tumor followed by chemotherapy, then a second look, and if necessary, third-look procedures may result in preservation of functioning renal tissue.