Head trauma in children with congenital coagulation disorders.

Bleeding is the most frequent cause of death in children with congenital coagulation disorders, and intracranial (IC) hemorrhage accounts for the majority of mortality in all age groups. Even minor head trauma may produce significant IC pathology. Immediate diagnosis and rapid medical management are mandatory if morbidity and mortality are to be minimized. Although computed tomographic (CT) scans provide accurate diagnostic information, reliable criteria for the use of this expensive technology in children with hemophilia and von Willebrand's disease have not been defined. In this study the clinical symptoms and the time of initial assessment and therapy of head-injured children with congenital coagulopathies were evaluated and correlated with CT findings. Between 1985 and 1992, 123 patients with hemophilia A, hemophilia B, or von Willebrand's's disease received follow-up at this institution. One hundred nine episodes of head injury were recorded in 43 patients, and 66 CT scans were obtained. The most frequent mechanism of injury was a simple fall at play (62%). Only 5 patients had an IC injury demonstrable with CT (4.5% of 110 episodes). Vomiting was reported in 4 of 5 patients with IC hemorrhage (ICH), and all 5 presented with an altered mental status (Glasgow coma scale [GCS] (mean) = 10) and focal neurological deficit. These findings were infrequently observed (vomiting, 5 of 105; GCS (mean) = 15; neurological deficits 0 of 105) in children who either did not undergo CT or whose CT scan results were normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Disseminated nonlymphoblastic lymphoma of childhood: a Childrens Cancer Group study, CCG-552.

PURPOSE: To assess the efficacy of a chemotherapy-only regimen in pediatric patients with disseminated non-lymphoblastic lymphoma and acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: Sixty-eight eligible patients with previously untreated disseminated non-lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty-five patients had small non-cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty-seven were stage III, six were stage IV, and 15 had B-ALL; 13 had central nervous system (CNS) involvement. RESULTS: Four year event-free survival (EFS) was 53% (SE +/- 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki-1-positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients. CONCLUSIONS: Advanced stage SNCCL requires better CNS-directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease-free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy-only strategies. DLCL patients do not need intensive CNS-directed chemotherapy.

Inadvertent intrathecal injection of daunorubicin with fatal outcome.

We report the first known case of daunorubicin administered directly into the human central nervous system. A 3 1/2-year-old female with pneumonia and otitis media was diagnosed with acute lymphoblastic leukemia and was admitted for antibiotics and chemotherapy. On the first day she inadvertently received a 17 mg intrathecal (IT) injection of daunorubicin. When the error was recognized about 1 hour later, her cerebrospinal fluid (CSF) was exchanged with sterile saline by barbotage, IT hydrocortisone was given, a subarachnoid catheter was inserted, and the CSF was allowed to drain for 36 hours. Only 5.6 mg (33%) of the dose was recovered from CSF, 2.7 mg as daunorubicin and 2.9 mg as the metabolite, daunorubicinol. Initially she was asymptomatic and induction therapy continued with vincristine, 1-asparaginase, prednisone, and IT methotrexate. One week after the daunorubicin injection she developed headache and irritability; CSF protein was 3.2 gm/dl. On the 12th day, she developed fungal sepsis and worsening pneumonia. On the 15th day, she became comatose with a flacid paraparesis, areflexia, and an ascending progressive bulbar palsy. A series of computerized tomography scans over 6 weeks showed increasing diffuse cerebral atrophy. Nerve conduction velocity studies were consistent with an axonal neuropathy. Despite her multiple concurrent medical problems, the timing and characteristics of neurologic damage suggest that IT daunorubicin caused progressive destruction of the nervous system.

The use of LIS for blood usage review. Experience in a children's hospital.

To comply with the requirements of the Joint Commission for the Accreditation of Healthcare Organizations (JCAHO) and to facilitate the review process, the authors designed a program to screen for the appropriateness of packed red cell (PRC) and platelet concentrate (PLT) transfusions. The purpose of this report is to describe the methodology of the review process. A quality assurance (QA) monitor was created in the Laboratory Information System (LIS) to screen indicators: hemoglobin for PRCs and platelet count for PLTs. Numerical value limits were defined to determine acceptable ranges. Each week, the LIS compiles a list of all patients who received transfusions and for whom the QA monitor determined that the values of the screened indicators were outside the defined appropriate limits. A detailed transfusion record is generated for each patient identified. During a six-month evaluation of this program, a total of 1,788 PRC and 3,109 PLT units were transfused. Of these, 582 PRC (32.5%) and 2,219 PLT (71.4%) units were within the acceptable guidelines. Lists for the remaining 1,206 PRCs and 890 PLTs were generated. Review of the transfusion record and other laboratory values from the LIS established the appropriateness of 1,052 PRC and 782 PLT transfusions. At the conclusion of the six-month period, the medical charts for 181 (11%) PRC and 108 (4.5%) PLT transfusions required chart review. This method provided major reduction in time of the transfusion review process. Similar guidelines may be used to monitor other transfusion products such as fresh frozen plasma.

Cytogenetic findings in congenital leukemia: case report and review of the literature.

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.

Pelvic and ovarian extramedullary leukemic relapse in young girls: a report of four cases and review of the literature.

Currently attention is focused on the testicle as a site of leukemic relapse. Leukemic involvement of the ovary has been described in several autopsy series with an incidence of 11-50% in patients with bone marrow relapse, but has rarely been reported during the clinical course of leukemia. In this report, four girls with childhood acute lymphocyte leukemia (ALL) who relapsed with a pelvic mass are presented. Three had marked ovarian infiltrates and the fourth had a presacral mass without ovarian disease. Involvement was also present in abdominal and pelvic lymph nodes, mesentery, omentum, and serosal surfaces. Two patients had infiltrates of the fallopian tubes and one had uterine involvement. Two patients had central nervous system disease and one patient has renal involvement at the time of relapse. Relapse occurred late in the course of disease. All patients had been in complete continuous remission prior to relapse. Retreatment was instituted in all patients and follow-up ranges from 18-135 months from the time of pelvic relapse. All patients have maintained continuous bone marrow remission from the time of initial diagnosis, and one patient died 18 months after ovarian relapse with significant extramedullary disease but no marrow involvement. This represents the first series of pelvic extramedullary leukemic relapse in females, an area of involvement that may be encountered more frequently in the future.

Stimulation of rat graft-versus-host reactions by polyinosinic-polycytidylic acid.

The effect of polyinosinic-polycytidylic acid (poly I:C) treatment on the rat graft-versus-host reaction (GVHR) initiated in parental to F1 hybrid strain combinations differing at either major or minor histocompatibility determinants were studied in three different protocols. 1 A GVHR initiated in juvenile (LBN)F1 recipients and treated concurrently with poly I:C alone produced neither splenomegaly nor dermatitis in these juvenile rats. (2) Pretreatment of L donors with a single injection of poly I:C 3 days before initiation of the GVHR enhanced resultant splenomegaly in the newborn (LBN)F1 recipients. A high poly I:C dose was inhibitory. (3) Newborn recipients which received lymphocytes from L donors and which were concurrently treated with poly I:C developed dermatitis at an accelerated rate. However, poly I:C alone given to newborns mimicked the GVHR by induction of a syndrome characterized by splenomegaly, dermatitis, thymic involution, and body growth retardation. The parental L and (LF)F1 hybrid strain combination differing only at a minor histocompatibility determinant or in an isogenic hybrid combination (LBN)F1 leads to (LBN)F(1) developed no GVHR when recipients were treated with poly I:C. We conclude that poly I:C can stimulate a rat GVHR initiated with unsensitized donor cells differing at a major histocompatibility locus.

Runt syndrome induced in the rat by polyinosinic-polycytidylic acid.

Polyinosinic with polycytidylic acid (poly l with poly C), a double-stranded synthetic RNA, produced in newborn rats a runt syndrome characterized by mortality and retarded growth rates of the total body, thymus, and kidneys. In contrast, it induced a hyperplasia in the epidermis and in the spleen. Within 10 days of treatment, the epidermis became 2 or 3 times thicker and the spleen mass was increased by 50%. The epidermal hyperplasia involved all layers, but hair follicles were excluded. Splenic hyperplasia did not result from accelerated erythropoiesis. Double-stranded RNA was required; single-stranded homopolymers were ineffective. Theophylline, a phosphodiesterase inhibitor, did not potentiate the effects. The uptake of iododeoxyuridine-125 was not enhanced in the hyperplastic epidermis or spleen. Thus we concluded that poly l with poly C can retard the growth of some organs in newborn rats, but that it causes epidermis and spleen to accumulate cells. The cytokinetic mechanisms involved in these contrasting effects were not clear.