Streptozotocin (NSC-85998) in children with acute lymphocytic leukemia. A Southwest Oncology Group study.

Streptozotocin (NSC-85998), a nitrosourea antibiotic, was given to 18 children with acute lymphocytic leukemia in relapse in a dose of 500 mg/m2/day intravenously every day for five days. There were no responses in 14 fully evaluable patients. The principal toxicity consisted of gastrointestinal disturbances. Based on our findings and those of others in adults, steptozotocin appears to play no role in the management of acute lymphocytic leukemia.

Cranial hemophilic pseudotumor. Case report.

Hemophilic pseudotumor is a rare complication of hemophilia occurring in 1% to 2% of individuals with a severe factor VIII or IX deficiency. This pseudotumor has been defined as a progressive cystic swelling involving muscle that is produced by recurrent hemorrhage and may be accompanied by roentgenographic evidence of bone involvement. The case is presented of a 12-month-old child with mild factor VIII deficiency (10% of normal factor VIII activity), who developed a pseudotumor of the skull.

Anemia of chronic renal failure.

Anemia is one of the most characteristic and visable manifestations of chronic renal failure. Investigators in the past decade have provided a better understanding of this anemia. The etiology of the anemia of chronic renal failure has three facets: first is reduced erythropoietin production by damaged kidneys; second is the presence of inhibitors to red blood cell (RBC) production in uremic serum; and third is red blood cell hemolysis. Unfortunately, transfusion therapy with its expense and risk of transmissable viral disease remains the mainstay of management for symptomatic anemia. Other modalities include dialysis, androgens, histidine supplementation, and erythropoietin replacement.

Comprehensive care for patients with hemophilia: an expanded role in reducing risk for human immunodeficiency virus.

Hemophilia is an inherited coagulation disease that affects approximately 1 in 5,000 to 10,000 males worldwide. Chronic joint disease and other long-term complications of recurrent bleeding persist in patients with hemophilia despite improved and more available clotting protein concentrates. The best care can be provided to patients who are followed regularly in specialized treatment centers. Services of every "comprehensive" hemophilia treatment center (HTC) have expanded since previous treatment with clotting factor concentrates infected many hemophilics with the human immunodeficiency virus (HIV). Each HTC offers therapeutic, educational, and counseling expertise in care for the complications of HIV. A nationwide network of specialists now provides care for patients with hemophilia and related congenital abnormalities. In Region VI (Texas, Oklahoma, and Arkansas), the treatment centers and their affiliates provide medical, psychosocial, orthopedic/physical therapy, dental, and case management services. Extramural funded research programs provide care and laboratory testing at no cost to individual subjects.

Noninvasive evaluation of hemophilic pseudotumor of the pelvis.

Hemophilic pseudotumors are a rare complication of chronic bleeding disorders. Invasive diagnostic procedures such as angiography, needle biopsy, or laparotomy carry a high risk in this group. Computerized tomography (CT) and ultrasound are safe alternative methods of evaluation. We report the computerized tomography and ultrasound characteristics of one such pelvic lesions.

Combination chemotherapy study for remission maintenance in ALL: an evaluation of vincristine, cyclophosphamide and vincristine, cyclophosphamide, and BCNU: a Southwest Oncology Group Phase II Study.

Vincristine (VCR), cyclophosphamide (CP), and BCNU have antineoplastic activity in acute lymphocytic leukemia. In animal tumor systems, and in a clinical controlled study, vincristine and cyclophosphamide have been demonstrated to be more effective when given sequentially. In animal models, cyclophosphamide and BCNU have a synergistic effect if given simultaneously. In order to evaluate this potentially synergistic schedule in man, children with ALL in their second or greater remission were randomized to receive either a standard vincristine cyclophosphamide regimen (VCR 2 mg/m2 on day 1 and CP 450 mg/m2 on days 2 and 3) or this same regimen with the addition of 50 mg of BCNU given with the CP given on days 2 and 3. The standard two-drug regimen was given every 3 weeks and the potentially synergistic combination was given on a 4-week schedule. The median duration of remission (MDR) for the 18 children receiving the two-drug combination was 13.5 weeks, and for the 20 children receiving the potentially synergistic three-drug regimen combination, 15 weeks. With 95% confidence, the population MDR for the two-drug combination is from 63% to 125% of the population with the three-drug regimen. The toxicities of both regimens was tolerable. No statistically significant synergistic benefit was demonstrated in these patients with the addition of BCNU to cyclophosphamide.

A test for abnormal hemoglobins in umbilical cord blood.

This article describes a rapid, simple, and inexpensive method for testing the cord blood of infants for the common hemoglobinopathies by electrophoresis using cellulose polyacetate strips. In a study of 7,500 umbilical cord blood specimens, 11% were found to contain an abnormal hemoglobin. While the importance of evaluating cord blood in a screening program for hemoglobinopathies is evident, the procedure must be accurate, verified, and followed by proper counseling.

Serologic response to hepatitis B vaccine in children receiving multiple blood transfusions.

Three doses of the commercially available hepatitis B vaccine were administered to each of 43 anti-hepatitis B surface antigen antibody-negative children (including 32 hemophiliacs) who were regularly receiving blood product transfusions. Forty-two (98%) of them had demonstrable anti-hepatitis B surface antigen antibody in their serum, indicating that this group of patients responds favorably to the vaccine.

Therapeutic choices made by patients with end-stage cancer.

The Oklahoma Children's Memorial Hospital Oncology Service has developed a new approach for its patients with end-stage cancer. The emphasis is on the patients' acknowledgement of the progression of the disease and the imminence of death, and informed choice between the use of research drugs and no further chemotherapy. Forty-three patients between 6 and 20 years of age participated in a conference of this type. The results demonstrated that they understood that their health was declining. They decided about further therapy autonomously or together with their family. The majority of children who chose supportive care without chemotherapy and lived for a period of time, participated in activities at home as far as their state of health permitted. Severe depression and severe behavioral problems occurred rarely. There was evidence that this open approach enabled patients and family members to communicate openly with each other.

Neuroblastoma: therapy for infants with good prognosis.

Therapy was designed to achieve a high cure rate and to prevent serious therapeutic side effects for 11 infants younger than one year old with neuroblastoma who had a favorable prognosis (Evans Stages I, II, III, and IV-S). It consisted of surgery alone if the tumor was totally removed (one infant) and of surgery and low doses of cytoxan and vincristine for a period of 1 year if the tumor was incompletely removed (seven infants). In addition, radiation therapy was applied to unresected dumbbell tumors (three infants). All infants are alive without evidence of disease with the exception of one who died in an accident. The follow-up time varies from 2-8 years. The drug combination prevented recurrences in two infants whose tumor was reduced by surgery to less than 10% of the original size. In five infants, chemotherapy reduced the size of large residual tumor masses. Two of these masses were subsequently removed. The tumors of the three other infants recurred while on chemotherapy and were successfully eradicated by surgery or radiation therapy. Two infants were not treated according to this therapeutic plan. Although they had small residual masses after surgery, no chemotherapy was given. They are alive without recurrence of the disease 2 years or more after diagnosis. In summary, cure was achieved in these infants without intensive chemotherapy.

Serial sonograms to detect pancreatitis in children receiving L-asparaginase.

The clinical, laboratory, and ultrasonographic findings in children receiving L-asparaginase therapy were retrospectively reviewed and correlated to determine the diagnostic reliability and clinical usefulness of serial pancreatic sonograms in detecting L-asparaginase-induced pancreatitis. A total of 217 sonograms were obtained in 92 patients. Six of the 92 (6.5%) had L-asparaginase-induced pancreatitis. The diagnosis of pancreatitis was based solely on clinical symptoms in three patients, on clinical and laboratory findings in two, and on sonographic and laboratory findings in one. No confirmed cases of pancreatitis were detected solely by ultrasonography before clinical or laboratory evidence was obtained. Sonograms were useful only in confirming clinical and/or laboratory evidence of pancreatitis, but were of no value in making the early or preclinical diagnosis of drug-induced pancreatitis. We have discontinued the practice of obtaining routine serial pancreatic sonograms in children receiving L-asparaginase at our institution.

Transient white matter changes on MR images in children undergoing chemotherapy for acute lymphocytic leukemia: correlation with neuropsychologic deficiencies.

The cranial magnetic resonance (MR) images of 25 children with acute lymphocytic leukemia (ALL) who were undergoing chemotherapy were retrospectively studied to determine the frequency of white matter changes and to analyze the significance of these observed changes in predicting subsequent neuropsychologic deficiencies. MR images showed transient white matter abnormalities in 17 of the 25 patients during consolidation therapy. Twelve of 20 children showed neuropsychologic deficits. There was no correlation between white matter changes and neuropsychologic deficits. In the subgroup of children under age 5 years at the time of diagnosis, 10 of 11 showed neuropsychologic deficits, and eight of 11 had white matter changes. Children under age 5 who undergo chemotherapy for ALL are at high risk to develop neuropsychologic deficiencies. Age at diagnosis is a reliable predictor of subsequent neuropsychologic deficits.

ICRF-159 (razoxane) in the treatment of pediatric solid tumors: a Southwest Oncology Group study.

ICRF-159 is active in several animal tumor model systems and human adult malignancies. In this phase II study, ICRF-159 was given on a weekly schedule, 3000 mg/m2/day, orally in three divided doses at 6-hour intervals to 78 children with a variety of malignant neoplasms. Fifty-three patients were evaluable for tumor response. Toxicity was primarily hematopoietic and gastrointestinal. There were no responses in any of the eight patients with osteogenic sarcoma, four with lymphoma, five with Ewing's sarcoma, ten with neuroblastoma, or six with rhabdomyosarcoma. There was a transient partial response in one of four children with Wilms' tumor. Further trials with this drug using this schedule are not indicated for the common childhood solid tumors.

Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation.

Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, we report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by us, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, transitions at the dinucleotide CpG show the largest male predominance (11-fold). In contrast to single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males.

Cisplatin in recurrent pediatric brain tumors. A POG Phase II study. A Pediatric Oncology Group Study.

Forty-six evaluable pediatric patients with primary recurrent brain tumors resistant to standard therapy were treated with cisplatin, 60 mg/m2/day, X2 days every 3 to 4 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses, documented by computed tomography (CT) scan, were demonstrated in 4 of 10 patients with medulloblastoma and 3 of 15 patients with ependymoma. No activity was documented in astrocytic tumors. Dose limiting major toxicities were renal and auditory. It is recommended that the new analogues of cisplatin with less toxicity be studied in these tumors.

Risk factors for infection with HBV and HCV in a largecohort of hemophiliac males.

BACKGROUND: Before the implementation of donor screening and the development of effective virus-inactivation procedures, persons with hemophilia (PWHs) were at risk of infection with HBV and HCV transmitted through clotting factor concentrates. STUDY DESIGN AND METHODS: Data collected from the medical records of a cohort of 2,772 males with hemophilia who resided in six states of the United States were used to examine relations between demographic and clinical characteristics and laboratory markers of past or present infection with HBV and HCV using logistic regression. RESULTS: Test results were available for 60 percent of the cohort. Among those tested, 30 percent were positive for markers of HBV infection and 64 percent for HCV infection. Factors associated with increased odds of positive HBV markers and HCV infection were greater severity of hemophilia, larger amounts of factor use, and HIV infection. Markers of HBV infection persisted in birth cohorts as late as 1992 and those of HCV infections in birth cohorts through 1991. Compared to same-age US males, PWHs born between 1987 and 1989 were more likely to have markers of HBV and HCV infection. CONCLUSION: PWHs who received clotting factor concentrates before 1990 may be at risk for infection with hepatitis B or hepatitis C and should be tested.