Severe acquired vitamin K deficiency: a hypothesis for rapid response to therapy.

The potential mechanism underlying the rapid response to vitamin K replacement in acquired deficiency states is incompletely understood. To examine vitamin K metabolism, a 10-year-old boy with autoimmune enteropathy on oral vitamin K supplementation, who presented with profuse nosebleeds and calf tenderness, was evaluated. Laboratory analyses were consistent with severe vitamin K deficiency: vitamin K dependent protein (VKDP) levels < 5%, normal vitamin K epoxide level and depressed total prothrombin antigen (carboxylated and undercarboxyated forms). Intramuscular vitamin K (10 mg) was administered. Nine hours following therapy, VKDP levels corrected completely. Total prothrombin antigen increased indicating new prothrombin synthesis. However, the increase in the prothrombin-clotting assay far exceeded the increase in total prothrombin, supporting storage of undercarboxylated prothrombin in vitamin K deficiency states, with carboxylation and secretion after vitamin K replacement. Although this mechanism is known to occur in rodents, it has not been reported in humans. Our findings suggest a new potential mechanism of prothrombin metabolism in humans.

Extrarenal Wilms' tumor: an ultrastructural and immunoelectron microscopic case report.

Wilms' tumor is the most common malignancy of the genitourinary tract in children but the occurrence of extrarenal Wilms' tumor is extremely rare. Extrarenal Wilms' tumor, which by definition excludes a primary tumor in the kidney, has been reported less than fifty times. The ultrastructural appearance of renal Wilms' tumor has been well documented, but the present report is believed to be the first description of the ultrastructural appearance of extrarenal Wilms' tumor. The authors report, for the first time, localization of intermediate filament proteins (vimentin and cytokeratin) and epithelial membrane antigen (EMA) by immunoelectron microscopy in this neoplasm. Demonstration of the coexpression of vimentin and cytokeratin within the same blastemal cell, as well as the identification of desmosomes in a cell with vimentin intermediate filaments, suggests a relationship between stroma, blastema, and epithelia similar to that proposed in renal Wilms' tumor.

Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of childhood: a Pediatric Oncology Group Phase I/II study.

PURPOSE: The combination of ifosfamide (I) and etoposide (E) was useful in salvaging patients with recurrent/resistant malignant solid tumors of childhood. Carboplatin (C), active against a number of pediatric cancers, was added to I and E to form a three-drug combination called ICE to improve the response rate. PATIENTS AND METHODS: ICE, consisting of I 1.5 g/m2 plus E 100 mg/m2 i.v.q.d. x 3 plus C i.v. on day 3 only, was given in 21-28-day intervals. C was started at 300 mg/m2, and the dose was escalated in 25% increments, with three evaluable patients treated at each level. RESULTS: Ninety-two patients were enrolled in this phase I/II study between July 1990 and April 1993. A total of 331 courses of ICE was administered. Median courses of ICE received were three (range, 1-16). The maximum tolerated dose (MTD) for C when used in combination was found to be 635 mg/m2. The response rate for ICE at the MTD for C was complete response (CR) 26% and CR + partial response (PR) 53%. The response was even better in those who received C at the MTD: 32% achieving a CR and 63% a CR + PR. Pancytopenia was the dose-limiting toxicity. Thirteen episodes of bacterial infection were reported, none fatal. Only one patient developed a Fanconi-like syndrome. CONCLUSION: The MTD of C when used with I and E was found to be 635 mg/m2. The overall CR + PR rate for all patients treated at all C dose levels was 53%. Best responses were seen in non-Hodgkin's lymphoma, neuroblastoma, soft tissue sarcomas, and Wilms' tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Extraskeletal Ewing's sarcoma of primary cardiac origin.

A 13-year-old boy presented with cardiac tamponade. Echocardiography revealed a large mass extending from the right and left ventricles into a large pericardial effusion. Pathology confirmed the first reported case of a primary cardiac extraskeletal Ewing's sarcoma.

Rebound thymic hyperplasia five years after chemotherapy for Wilms' tumor.

Rebound thymic hyperplasia following chemotherapy is well documented, usually occurring within the first year. A delayed presentation makes distinction from an anterior mediastinal mass problematic in view of the increased risk of a second primary malignancy in pediatric cancer survivors. An unusual case of rebound thymic hyperplasia is described, presenting five years after completion of chemotherapy for Wilms' tumors.

Immunophenotypic characteristics of cerebrospinal fluid cells in children with acute lymphoblastic leukemia at diagnosis.

The presence of meningeal involvement in children with acute lymphoblastic leukemia (ALL) may have important prognostic and therapeutic implications. Conventional methods of diagnosing central nervous system (CNS) leukemia rely on the interpretation of cerebrospinal fluid (CSF) cell morphology, which may produce ambiguous results in the presence of minimal leukemic involvement. A methodology has been developed for immunophenotyping small numbers of CSF cells while preserving cell morphology. CSF samples from 33 children with CD10 (common ALL antigen [CALLA]) positive ALL were examined at initial presentation using both conventional morphology and this combined immunohistopathologic technique. Six (18%) of the samples contained lymphoblasts or cells considered morphologically suspicious for leukemic involvement. Nine additional samples (27% of the total) had normal CSF morphology, but contained increased numbers of CALLA positive cells. Twelve of the 33 samples were also examined for the simultaneous presence of nuclear terminal deoxynucleotidyl transferase (TdT) and demonstrated increased numbers of cells positive for both TdT and CD10. These data suggest that a large proportion of children with ALL may have abnormalities of CSF cells at initial diagnosis consistent with the presence of occult leukemic involvement.

The clinical spectrum of heterozygous protein C deficiency in a large New England kindred.

A family with a high incidence of venous thromboembolism was investigated. We performed medical evaluations on 184 of the 411 surviving members of the pedigree, which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their clinical histories of thrombosis. Subjects with antigenic levels of protein C less than 66% of a normal plasma pool were classified as having protein C deficiency. Positive thrombotic histories were found in 13 of the 46 family members determined to be protein-C deficient and in only five of their 138 biochemically unaffected relatives. Statistical analysis of the association between thromboembolic disease and protein-C deficiency was strongly positive chi 2 = 24.95, P less than .0001 with n = 184), indicating that heterozygous protein-C deficiency is an important independent risk factor for the development of thrombotic manifestations in this pedigree. However, the absence of thromboembolic manifestations in many of the protein-C deficient family members to date indicates that other, as yet undefined, factors must play an important role in the clinical expression of this disorder.

Fragile X syndrome and acute lymphoblastic leukemia.

Fragile X [Fra(X)] syndrome is an example of a heritable fragility syndrome associated with mental retardation. It is characterized by a fragile site on the X chromosome at Xq27-28. There have recently been three reports of malignant solid tumors associated with Fra(X) syndrome. We describe the first case of a hematologic malignancy [T-cell acute lymphocytic leukemia (ALL)] in a patient with Fra(X) syndrome. The possibility of a predisposition to malignancy in Fra(X) is discussed.

Parental attitudes about confidentiality in a pediatric oncology clinic.

Children and parents who attend pediatric oncology clinics often develop close relationships with other patients and may question clinic staff about another child's disease, therapy, or status. To assess parental attitudes concerning the dissemination of information by the clinic staff, questionnaires were mailed to the parents of all 154 patients who have attended pediatric oncology clinic since 1972. There were 100 (65%) responses including 77 from 99 living (78%) and 23 from 55 deceased patients (42%). Parents were asked whether clinic staff should respond completely to questions from other clinic parents regarding six aspects of their child's cancer. Percentages of parents who favored complete information sharing without their explicit consent about each of the aspects were as follows: diagnosis, 83%; medication/side effects, 85%; laboratory results, 66%; general status, 87%; occurrence of relapse, 77%; development of terminal phase, 67%. Neither the survival status (living v deceased) nor whether the patient was receiving therapy or not affected responses significantly. Benefit from receiving information about other children from clinic staff was reported by 82% of parents.

Haploidentical bone marrow transplantation for osteopetrosis.

HLA-matched bone marrow transplantation is an effective form of treatment for some patients with malignant osteopetrosis, a defect of osteoclast function. Following transplant, normal osteoclasts differentiate from donor-derived marrow stem cells and can function normally in some of these patients. For patients without an HLA-matched marrow donor, pharmacologic treatments have not yet proved effective. This article demonstrates that normal osteoclast function can be obtained following the transplantation of HLA-nonidentical marrow that has been purged of T lymphocytes in vitro.

Evaluation of the capillary microhematocrit as a screening test for anemia in pediatric office practice.

The capillary microhematocrit test is widely used to screen pediatric patients for anemia. Recently, it has been suggested that this method produces spuriously elevated values compared with venous hematocrits measured by a Coulter electronic counter and might consequently fail to detect children who are truly anemic. To address this issue we studied 66 white children 9 months to 14 years of age whose capillary hematocrits were either below, equal to, or one or two points above the lower limit of normal for age. Venous specimens were obtained simultaneously with the capillary sample; hemoglobin, hematocrit, and mean corpuscular volume results were obtained using a Coulter electronic counter. Using published standards of venous hemoglobin, we determined the sensitivity, specificity, and predictive values of the capillary microhematocrit in this population of patients with low or borderline values. Twenty of the 66 patients had venous hemoglobin values less than the lower limit of normal. The sensitivity of the microhematocrit was 90.0%; the specificity was 43.5%. The predictive values for a normal (negative) hematocrit was 90.1%; the predictive value for a low (positive) hematocrit was 40.9%. We conclude that the microhematocrit method using capillary blood will miss very few patients with significantly low venous hemoglobin values and is thus an acceptable screening test for anemia. Because it does not require expensive equipment or special skill to obtain the specimen or perform the test, it is ideal for physicians' offices or nonhospital-based clinics.

Gastric outlet obstruction in chronic granulomatous disease of childhood.

A patient was diagnosed with gastric outlet obstruction (GOO) 17 months after the neonatal diagnosis of chronic granulomatous disease (CGD). Gastric outlet obstruction was the first clinical manifestation of CGD in this patient. Twenty-three percent of the 17 patients with GOO complicating CGD described in the literature were found to present with GOO before any other clinical manifestations of CGD. The diagnosis of GOO can be established by ultrasound and, if necessary, upper gastrointestinal roentgenogram or gastroscopy. A nonsurgical approach to management is suggested. The diagnosis of CGD should be considered in an infant or child who has GOO.

Second or subsequent remission with a disease-free survival of 5 years or longer in acute lymphocytic leukemia of childhood: results of a national survey.

A national survey was conducted to determine the number of children with acute lymphocytic leukemia who have survived 5 years or longer in their second or subsequent remission. Seventy-two such patients were identified. The clinical and laboratory characteristics of these patients as well as their therapy are described. It is concluded that long-term second or subsequent remission may occur more frequently than previously appreciated.

8;14 chromosome translocation in a negative bone marrow aspirate from a patient with Burkitt's lymphoma.

A patient with Burkitt's lymphoma is described who, on presentation, had a bone marrow aspirate which did not show abnormal cells. Cells from the bone marrow were cultured and an 8;14 chromosome translocation was identified. This finding allowed us to upgrade the stage of disease from III to IV with therapeutic as well as prognostic implications.

Infantile lymphoblastic leukemia with t(4;11) and septate uterus, double cervix, and double vagina: case report and review of the literature.

Translocation between chromosomes 4 and 11 has been associated with an aggressive subtype of acute lymphoblastic leukemia. To date, 32 cases have been reported, 12 of which have been in infants. We report the 13th infantile case and the first associated with a somatic abnormality (septate uterus with double cervix and double vagina).

Depletion of T cells from human bone marrow with monoclonal antibody CT-2 and complement.

CT-2 mouse monoclonal antibody to the E-rosette receptor was used with complement to deplete bone marrow of E-rosette-positive cells (T cells). Depletion of E-rosette-positive cells was complete and nontoxic to hematopoietic progenitor cells. Depletion of E-rosette-positive cells with CT-2 may decrease the severity of graft-versus-host disease following bone marrow transplantation and extend the application of bone marrow transplantation to those without HLA-identical donors.