Prophylaxis and therapy with factor VII concentrate (human) immuno, vapor heated in patients with congenital factor VII deficiency: a summary of case reports.

Hereditary factor VII deficiency is a rare autosomal recessive condition, usually associated with normal or reduced levels of a functionally defective molecule. The available means of treating this condition in North America presents serious health risks to the patient. Transfusion with fresh frozen plasma carries a risk of volume overload and a significant risk for viral transmission. Sustained prothrombin complex therapy is associated with a high risk for thrombogenic complications. This communication describes the use of Factor VII Concentrate (Human) Immuno, Vapor Heated--an intermediate purity factor VII concentrate from Immuno A.G.--for the treatment of 13 patients with factor VII deficiency. Treatment regimens described include those for long-term prophylaxis (three children), acute hemorrhages (two children, one adult), peripartum prophylaxis (one patient), and surgical coverage (two children, four adults). Prophylaxis and therapy were successful in all cases, the medication was well-tolerated, and there were no complications. In the three cases of long-term prophylaxis in children, doses of 10-50 IU/kg were given one to three times a week; one patient has undergone long-term prophylaxis for approximately 8 years, one patient for 1 year, and one patient for 1 1/2 years. Three cases in which Factor VII Concentrate was principally used for treatment of acute episodes of bleeding are described. One infant received Factor VII Concentrate on about 50 occasions for treatment of mucosal bleeding; a correction to 40-100% resulted in cessation of bleeding within 15 min in all cases. For treatment of an episode of intracranial bleeding, an 8-year-old boy received a dose of 37 IU/kg Factor VII Concentrate every 6 hr for peak factor VII levels of approximately 100% and troughs as low as 4% over the 11-day treatment period. A 37-year-old adult male with intracranial bleeding received alternating doses of 16 IU/kg and 8 IU/kg every 6 hr for 10 days with peak factor VII levels in the upper thirties (%). The peak favor VII level during surgical coverage with Factor VII Concentrate (neurosurgery, open reduction of ankle bones, dental surgery, pituitary adenoma surgery, closed liver biopsy) was approximately 100% in all cases, with trough levels ranging from 8 to 65% over treatment periods of 24 hr to 16 days using treatment intervals of 6-12 hr.

Cyclophosphamide/doxorubicin vs. cisplatin/teniposide in the treatment of children older than 12 months of age with disseminated neuroblastoma: a Pediatric Oncology Group Randomized Phase II study.

This prospective study was designed to estimate the response rates and to compare two drug pairs, cyclophosphamide/doxorubicin (Cy/A) and cisplatin/teniposide (P1/VM) in previously untreated patients with disseminated neuroblastoma > 12 months of age at diagnosis. Estimated complete clinical response rates after five courses of therapy were 13% (70 patients) and 22% (64 patients) for Cy/A and P1/VM, respectively (P = 0.17). After surgical removal of residual tumors in patients with partial response, the complete response rates were 27% and 34% (P = 0.50), respectively. The overall CR/PR rates after induction and surgery were 59% and 73% (P = 0.077). There was no significant difference in event free survival (P = 0.48) or survival (P = 0.40). Five year survival on the two arms were 14% (SE = 5%) and 12% (SE = 4%), respectively. Toxicity was significant but manageable. The Cy/A arm had significantly higher hematopoietic toxicity but significantly lower GI toxicity. Significant allergic reactions were seen with the P1/VM arm, none in the Cy/A arm. Given the activity of these two regimens, further therapy with a combination of these regimens is suggested.

Serum lactate dehydrogenase in childhood neuroblastoma. A Pediatric Oncology Group recursive partitioning study.

On the basis of an extensive recursive partitioning analysis of 668 patients with newly diagnosed neuroblastoma registered on Pediatric Oncology Group (POG) studies between October 1981 and May 1987, four major subsets of patients were created. Important prognostic factors included the patient's stage of disease, age, and level of serum lactate dehydrogenase (LDH). After adjusting for these factors, no other clinical prognostic factors were significant. The implications for protocol design are that (a) fine tuning of current therapy should be sought for the two favorable disease patient subsets, while (b) novel aggressive therapies are needed for the two unfavorable disease patient subsets where the overwhelming majority are dying. This article may serve as a model for others investigating prognostic factors. The data were divided into two subsets: one was used for an exploratory analysis; the other was used to confirm the exploratory findings. Despite spite the large number of statistical tests performed, the likelihood that the findings can be attributed to chance can be dismissed as virtually zero.

Primary extrarenal Wilms' tumor in children.

We report three additional cases of primary extrarenal Wilms' tumor and review those cases previously documented. Analysis of the location, histopathology, treatment, and survival of these cases supports the following conclusions: Wilms' tumor may occur in an extrarenal location without primary renal involvement and must be included in the differential diagnosis of abdominal, pelvic, and inguinal masses; an extrarenal location supports a more frequent occurrence of ectopic metanephric blastema than was previously recognized or origin of Wilms' tumor from a more primitive mesodermal tissue; and the natural history and prognosis of extrarenal and renal Wilms' tumors appears similar.

Epstein-Barr virus-associated lymphoproliferative disorder. Applications of immunoperoxidase and molecular biologic techniques.

A 17-year-old boy with fever and cervical lymphadenopathy developed multiple-organ failure and died three weeks after hospital admission. A lymph node biopsy specimen demonstrated a florid immunoblastic infiltrate that was suspicious for a malignant lymphoma. By using immunoperoxidase and molecular biologic techniques, evidence was presented for an Epstein-Barr virus-associated lymphoproliferative disorder.

Multifocal ganglioneuroblastoma coexistent with total colonic aganglionosis.

Neuroblastoma and Hirschsprung's disease are considered aberrations of neural crest cell growth, migration, or differentiation. Their coexistence, however, is rare. We present the case of an only child with total colon Hirschsprung's disease diagnosed shortly after birth, who was found to have noncontiguous ganglioneuroblastomas without metastases at age 16 months. The spectrum of neural crest anomalies, long segment Hirschsprung's disease and multifocal neuroblastoma, in this child is unique and previously unreported.

Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma.

We studied the relation between the DNA content of neuroblastoma cells and the response to therapy in 35 infants under one year of age with a diagnosis of neuroblastoma. Using flow cytometric techniques, we found that in 27 cases the primary malignant stem line consisted of neuroblasts with hyperdiploid DNA content, ranging from 1.07 to 2.42 times the finding in normal diploid cells. All remaining cases had diploid stem lines. Diploidy was more common in infants with clinical Stage D neuroblastoma (metastases beyond regional lymph nodes) than in those with other, less advanced stages: 6 of 10 as compared with 2 of 25 (P = 0.003). Of 17 evaluable patients with unresectable hyperdiploid tumors, 15 had complete responses and two had partial responses to cyclophosphamide and doxorubicin; six others with diploid tumors did not respond (P = 0.00001). We also found that each of the four infants with Evans' Stage IV-S neuroblastoma, an unusual form of disseminated neuroblastoma with a relatively good prognosis, had hyperdiploid tumor cells of clonal origin. We conclude that in neuroblastoma of infants, hyperdiploidy of tumor cells is associated with a better response to chemotherapy than is diploidy.

Clinical and immunological correlates of leukemia cutis in childhood.

Clinical features of three children with acute lymphoblastic leukemia complicated by leukemia cutis are described. All three patients appeared to have null cell disease, in contrast to adult cutaneous lymphoproliferative diseases which are generally T-cell disorders. Morphologically normal bone marrow specimens from one of these patients plus an additional four patients with isolated extramedullary relapses were also studied and found to be reactive to antisera defining leukemia associated antigens and/or human Ia-like antigens during six of eight relapse episodes. Such data may imply the need for systemic as well as local therapy when "isolated" extramedullary relapse occurs.

Receptors for peanut agglutinin (Arachus hypogea) in childhood acute lymphoblastic leukemia: possible clinical significance.

The presence of lymphocyte receptors for peanut agglutinin in significant numbers (greater than 15%) was identified on leukemic cells from T-cell acute lymphoblastic leukemia (T-ALL) (3/4), B-cell ALL (B-ALL) (2/4), null cell ALL (8/17), and on normal fetal thymic lymphocytes but not on normal human peripheral blood lymphocytes. Peanut agglutinin (PNA) binding was blocked specifically on leukemia lymphoblasts and thymic lymphocytes by the addition of galactose to the medium. When all immunologic subgroups of ALL are combined, preliminary data suggest that of the 13 ALL patients having greater than 15% PNA-positive lymphoblasts, 8 had relapsed, whereas none of the 12 ALL patients with less than 15% PNA-positive cells have recurrent disease at this time. It is likely that analysis of PNA receptors on ALL lymphoblasts may be a useful adjunct to the existing clinical and immunologic prognostic indicators.

Human acute myelogenous leukemia antigens defined by simian antisera: evidence for leukemia-associated antigens distinct from immune response-associated alloantigens.

Leukemic blasts from a patient with acute myelogenous leukemia (AML) and peripheral blood T- and B-lymphocyte subpopulations from his genetically identical normal twin were analyzed with the use of the simian antiserum-defining AML antigens and a rabbit antiserum to immune response-associated (la)-like antigens. Blast cells from the patient consistently reacted with both reagents, whereas the B-lymphocyte populations from the patient's normal identical twin reacted only with the rabbit anti-la serum and in no instances reacted with the antiserum to AML cell antigens. Blast cells from the AML patient significantly stimulated the lymphocytes of his normal twin and his own remission leukocytes, whereas the cells from the normal twin failed to stimulate the cells of the patient. These results suggested the existence on AML cells of tumor-associated antigens that are distinct from various other well-characterized normal human alloantigens and differentiation antigens including B-cell antigens. Changes were reported in the expression of leukemia-associated antigens and Ia-like antigens on the cells of an AML patient undergoing chemotherapy as well as in the ability of the simian antisera to distinguish antigens specific for myeloid leukemias from lymphocytic types of leukemias.

Acute idiopathic thrombocytopenic purpura in children.

Acute idiopathic thrombocytopenic purpura (ITP) characteristically follows a viral illness in preschool children. The exact role of viruses in the pathogenesis of this disorder remains uncertain, but the finding of markedly elevated levels of platelet-associated IgG serves to distinguish it from the chronic form of the disease and permits speculation on the mechanisms of platelet destruction. Although the spleen is important in both antibody production and platelet destruction, bone marrow synthesis of IgG has also been shown to be increased. The clinical course may be alarming, but mortality is low and prognosis excellent. Controversy has surrounded the role of steroids in the management of acute childhood ITP in retrospective studies. Controlled studies, however, indicate that thrombocytopenia is reversed sooner in treated patients. New assays for platelet-associated IgG offer new insights into this disorder and will allow delineation of acute and chronic disease at the time of diagnosis.