Raymond Tannous

Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children's Cancer Group protocol 9942: A report from the Children's Oncology Group†

Standard therapy for childhood intracranial ependymoma is maximal tumor resection followed by involved‐field irradiation. Although not used routinely, chemotherapy has produced objective responses in ependymoma, both at recurrence and in infants. Because the presence of residual tumor following surgery is consistently associated with inferior outcome, the potential impact of pre‐irradiation chemotherapy was investigated.

Immune Thrombocytopenia and Elemental Mercury Poisoning

Three cases of severe mercury toxicity occurring within a family are reported. Two cases of thrombocytopenia occurred in this family and represent the second such report in the literature of an association between elemental mercury toxicity and thrombocytopenia. Three of the children presented with a combination of dermatologic and neurologic manifestations reminiscent of acrodynia or pink disease. Each of the four children in this family were treated with dimercaptosuccinic acid. The hazard of vacuuming spilled mercury and appropriate clean-up procedures are described.

Acute monoblastic leukemia: a unique subtype--a review from the Childrens Cancer Study Group.

The acute non-lymphocytic leukemias (ANLL) are generally treated as a homogeneous group. However, the literature is replete with articles alluding to distinctive features of acute monoblastic leukemia (AMoL). This review addresses the unique clinical, laboratory, epidemiological, and therapeutic features of AMoL. Leukemic monoblasts are distinguished from other cells in the myelocytic series by physical properties such as greater adhesiveness, deformability, and motility. Patients with AMoL often exhibit hyperleukocytosis, disseminated intravascular coagulation, and extramedullary involvement, particularly in the skin, gingiva, and central nervous system (CNS). AMoL occurs predominantly in adults over 40 and children under 10, fifty percent of whom are under 2 years of age at diagnosis. Its relatively common occurrence in infants parallels the high rate of proliferation of monocytes in that age group. Additionally, its occurrence in young children appears to be associated with in utero exposure to marijuana and parental exposure to pesticides and solvents. Therapeutic results are generally poor due to high rates of fatal complications during induction, induction failures, and frequent extramedullary and medullary relapses. This poor outcome is particularly noted in infants. Higher remission induction rates attained with epipodophyllotoxins and incorporation of bone marrow transplantation have not yet resulted in substantial improvement of long-term outcome. Recurrence of disease in the CNS is minimized by the use of intensive CNS presymptomatic treatment, usually incorporating irradiation. Our review suggests that unique and innovative treatment strategies are needed to improve outcome for patients with AMoL.

Protracted radiotherapy treatment duration in medulloblastoma

From 1970 to 1997, 63 patients with medulloblastoma were treated with craniospinal irradiation followed by a posterior fossa boost. There were 38 males and 25 females with a median age of 9 years (range, 8 months to 53 years). Stage was T1-T3a in 50 (79%) and M0 in 38 patients (60%) according to the Chang staging system. Gross total resection of the primary tumor was achieved in 33 (52%) and median posterior fossa dose was 54 Gy, with 55 (87%) receiving ≥50 Gy. Median radiotherapy treatment duration was 49 days (range, 30–104 days) with 35 patients (56%) completing radiotherapy in <50 days. The most common reasons for a protracted radiotherapy treatment duration ≥50 days were hematologic toxicity (46%) and use of <1.6 Gy fraction size per day (29%). Chemotherapy was used in 22 (35%). Median follow-up time was 10.8 years (range, 2–28.5 years). The 5- and 10-year freedom from progression rates were 58% ± 13% and 50% ± 13%, respectively, whereas the 5- and 10-year posterior fossa control rates were 61% ± 12% and 54% ± 13%, respectively. On multivariate analysis, age ≥3 years, M0 status, ≥50 Gy PFB dose, radiotherapy treatment duration <50 days, and use of chemotherapy correlated with better freedom from progression and posterior fossa control rates. The 5- and 10-year freedom from progression rates were 67% ± 15% and 64% ± 16%, respectively, for patients with radiotherapy treatment duration <50 days and were 42% ± 20% and 29% ± 18%, respectively, for duration ≥50 days (p = 0.0026, log-rank test). The 5- and 10-year posterior fossa control rates were 70% ± 15% and 70% ± 15%, respectively, for radiotherapy treatment duration <50 days and 46% ± 20% and 33% ± 19%, respectively, for duration ≥50 days (p = 0.0037, log-rank test). In addition to age ≥3 years, M0 stage, use of adjuvant chemotherapy, and posterior fossa dose ≥50 Gy, our findings also reveal that radiotherapy treatment duration <50 days has a favorable prognostic outcome in patients with medulloblastoma.

Rectosigmoidal colitis in common variable immunodeficiency disease

SummaryA patient with common variable immuno-deficiency disease is described with severe colitis confined to the rectosigmoid region. Inflammation was extensive in the regions involved and exhibited a character that we believe is most unusual. Inflammation was transmural in the regions involved. Macrophages were the major inflammatory cells, and no granulomas or giant cells were seen. Although the disorder seemed distinct from either ulcerative colitis or Crohns disease, the colitis responded favorably to oral azulfidine, prednisone, and to steroid enemas.

SHARED MANAGEMENT OF CHILDREN WITH CANCER: A 15 YEAR REASSESSMENT. 928

Background: In 1976, to provide access to modern treatment for children with cancer in a rural setting, a system was designed to divide treatment responsibilities between university-based pediatric oncologists and community-based primary care physicians. Under this system, the diagnosis and assignment to a treatment regimen is carried out at the university while community-based physicians delivery over 75% of the chemotherapy. Because managed care limits access to subspecialists and reduces the flexibility for collaboration between subspecialists and primary care physicians, assessment of the shared management system was undertaken.

Development of chemotactic factor inactivation - a fetal lamb model.

Summary: To study the developmental pattern of chemotactic factor in-activator (CFI) activity, although avoiding the effects of labor and delivery, serial blood samples were obtained from eight chronically catheterized lamb fetuses, 13 pregnant, and 13 nonpregnant ewes. The biologic profiles of adult sheep neutrophils in response to sheep C5-derived chemotactic fractions (C5-fr) were determined by the chemotactic and lysosomal enzyme release assays. CFI activity in sheep plasma was characterized and measured by the % inhibition of C5-fr-induced neutrophil lysosomal enzyme release.The chemotactic and enzyme release profiles of sheep neutrophils paralleled those of human neutrophils. Sheep plasma was shown to contain a CFI-like activity similar to that in human plasma.Mean CFI activity was higher in the plasma of pregnant ewes as compare to nonpregnant ewes (7.60 versus 5.15%, P < 0.001). Higher CFI levels (39.5%) were shown in the plasma of chronically catheterized fetuses early in the third trimester of pregnancy (109 days gestational age). These fetal levels decreased progressively to attain normal adult levels at fetal maturity (147 days gestational age) and no significant changes were noted at or after birth. Because identical changes occurred in all chronically catheterized fetuses, a developmental pattern was defined for CFI. Control CFI levels from six acutely catheterized fetuses did not differ from those predicted by the developmental pattern. Thus, the changes in CFI activity were not related to the chronic catheterization or to events surrounding labor and delivery; rather CFI levels correlated best with fetal immaturity.CFI levels correlated inversely with ability of zymosan activated plasma to induce neutrophil chemotaxis (r = —0.96, P < 0.01), suggesting that CFI plays a major role in the regulation of leukocytes chemotaxis.These data confirm previous findings in human neonates and provide a model for future studies. Further studies into the biology of the changes in CFI activity in the fetus and the influence of such high risk factors as prematurity, fetal distress or premature rupture of membranes should enhance our understanding of the immunocompromised neonate.

883 DECREASED CHEMOTACTIC ACTIVITY IN NEONATAL PLASMA: ROLE OF CHEMOTACTIC FACTOR INACTIVATOR AND COMPLEMENT LEVELS

Compared to adult plasma, the chemotactic activity of neonatal zymosan activated plasma (ZAP) is decreased. Consequently, we evaluated the role of chemotactic factor inactivator (CFI) and complement levels in this defect. Plasma of 15 neonates and 15 adults were studied. The chemotactic activity of ZAP was measured under agarose, using adult neutrophils as target cells. CFI levels were determined by incubating 0.1 μl plasma with 50 μl C5-derived chemotactic fractions and then measuring the percent decrease in glucosaminidase release from cytochalasin B-treated neutrophils. C3, C5, factor B, properdin and properdin convertase were determined immunochemically; and Cl, C2, C4, C3-9 and CH50 by hemolytic assays in 10 of these infants and adults.Compared to adult plasma, the chemotactic activity induced by infant plasma was decreased (80 ± 7% of control [mean ± SD], vs. 95 ± 3%, p < 0.001), CFI levels were increased (19 ± 6 vs. 7.5 ± 3, p < 0.001), and complement component levels were decreased (p < 0.05), except for C2. The chemotactic activity correlated inversely with CFI levels (r = -0.958, p < 0.001). After adjusting for the effects of CFI, there was no significant correlation between the chemotactic activity and any of the complement components tested. Thus, differences in CFI, rather than in complement levels, accounted for the differences in chemotactic activity between infant and adult plasma.