Successful combination therapy of a proximal haemophilic pseudotumour with surgery, radiation and embolization in a child with mild haemophilia A.

We describe the management of a young boy with mild haemophilia A and a massive iliac pseudotumour with a multi modality approach involving factor replacement, radiation therapy, embolization and surgery. The patient was initially treated with recombinant factor VIII and radiation therapy. Because of inadequate response and worsening of bony erosion, the patient had a preoperative embolization followed by surgical excision. The surgical procedure was associated with minimal blood loss and the patient had a relatively smooth postoperative course with no physical morbidity. This case illustrates successful aggressive management of a large, proximally located pelvic pseudotumour, which resulted in an excellent outcome despite the need for a normally morbid operation.

Oral contraceptives: a cause of hyperbilirubinemia in stem cell transplant patients.

Conjugated hyperbilirubinemia in the clinical setting of hematopoietic stem cell transplantation can have multiple etiologies that may prompt various therapeutic interventions. Two patients who received short courses of a high-dose estrogen-progesterone combination to treat breakthrough menstrual bleeding during transplant are reported. Conjugated hyperbilirubinemia developed in both patients within days of beginning therapy and resolved after the ethinyl estradiol and norgestrel (Ovral; Pharmacia and Upjohn, Kalamazoo, MI, U.S.A.) was discontinued. In one of the patients, this occurred on three separate occasions during the course of transplantation. Recognizing the cholestatic effect of estrogens during transplantation may prevent unnecessary alterations in therapy beyond the simple discontinuation of these medications.

Treatment of childhood acute immune thrombocytopenic purpura with anti-D immune globulin or pooled immune globulin.

OBJECTIVE: To evaluate the effectiveness of initial treatment of children with acute immune thrombocytopenic purpura (ITP) with anti-D immune globulin (anti-D) or pooled IgG immune globulin (IVIg). STUDY DESIGN: The medical charts of 33 children diagnosed with acute ITP from May 1995 to October 1997 were reviewed. Patient data were eligible for analysis if, for the new diagnosis of acute ITP, the patient had received either anti-D at 45 to 50 microg/kg (WinRho SD, NABI) or IVIg at 0.8 to 1 g/kg (Gammagard SD, Baxter-Highland). The platelet response time for each treatment group was compared by the Mann-Whitney U test. RESULTS: Time to achieve a platelet count >/=20 x 10(9 )/L (20,000/mm3 ) was 1.54 +/- 0.51 days in the IVIg group (n = 13) and 1.26 +/- 0.82 days in the anti-D group (n = 14) (P =.34). Time to achieve a platelet count >/=40 x 10(9 )/L (40,000/mm3 ) was 1.77 +/- 0.74 and 1.49 +/- 1.01 days for the IVIg and anti-D groups, respectively (P =.32). Children given IVIg were hospitalized for 2.1 +/- 0.87 days, whereas those given anti-D were hospitalized for 1.94 +/- 1.08 days. A net decrease in hemoglobin concentration was observed after receipt of IVIg (9.1 +/- 7.3 g/L [0.91 +/- 0.73 g/dL]) and after anti-D therapy (4.5 +/- 10.3 g/L [0.45 +/- 1.03 g/dL], P =.23). No patient required intervention for hemolysis. CONCLUSIONS: In this retrospective analysis anti-D was as effective as IVIg for the treatment of acute ITP in children. However, randomized, controlled trials are needed to establish the role of anti-D in the treatment of acute ITP in children.

Rhabdomyosarcoma in children--a ten year review.

PURPOSE: The purpose of this study is to retrospectively analyze all pediatric patients with Rhabdomyosarcoma (RMS) of various anatomic sites, treated in our department over a 10-year period, for treatment results. Anatomical site, group, and gender are individually analyzed as prognostic indicators of overall survival. MATERIALS AND METHODS: Sixteen rhabdomyosarcoma patients diagnosed by biopsy or surgical resection were reviewed. All patients were treated according to assigned IRS protocols except one. Age ranged from 1 to 19 years with a median age of 4 years. Ten patients were male and 6 were female, 14 were white and 2 black. Anatomic sites included six from the head and neck region, seven in the trunk and three in the extremities. Embryonal RMS was present in all but one which was classified as undifferentiated. All patients had surgery (biopsy-5, partial-1 or complete resection-10) and chemotherapy (VA, VAC, VAC plus Adriamycin, or VAC plus Adriamycin, CIS Platinum and VP-16). Ten patients received irradiation consisting of 3060 cGy to 5850 cGy using shrinking fields with 1.8 to 2.0 Gy/day/5 day/wk. RESULTS: Patients tolerated the treatment well and there were no late complications. Only one patient had a recurrence in the primary site with a median follow-up of 61 months (range 5-118 months) for the whole group. The 5-year disease free survival and actuarial survival for all patients treated were 73% and 87% respectively, with four patients developing metastasis and three of those dead of disease. CONCLUSION: This study represents a heterogeneous group of patients with RMS treated over a 10-year-period. The results correlate with those found in the most recent published IRS data for embryonal histology. From experience gained from earlier studies, newer IRS protocols have tailored treatment protocols to specific site with more intense therapy used for difficult treatment sites.

Umbilical cord blood transplantation: providing a donor for everyone needing a bone marrow transplant?

BACKGROUND: Bone marrow transplantation (BMT) has been limited in the past by the availability of matched donors for patients. Over the past decade, the use of umbilical cord blood (UCB) as a source of hematopoietic stem cells has revolutionized the field of BMT, providing a source of hematopoietic stem cells for an increasing number of patients in need of a transplant. RESULTS: Umbilical cord blood transplantation (UCBT) appears to result in sustained engraftment of donor hematopoiesis similar to results achieved with marrow and peripheral blood hematopoietic stem cells. Early results indicate that UCBT is associated with a lower incidence and less severity of graft-versus-host disease than other sources of stem cells, potentially decreasing the morbidity and mortality of BMT. As the potential of UCBT has been realized, cord blood storage facilities have been established to provide UCB. The rapid emergence of UCBT has transformed a waste product of birth into a life-saving resource. Its use, however; has raised numerous ethical and medical concerns unique to this alternative source of stem cells. CONCLUSIONS: Umbilical cord blood transplantation represents a major advance in providing another stem cell source to patients in need of allogeneic hematopoietic stem cell transplantation. As with all new technologies, UCBT will have to be carefully studied over the next several years to determine its safety, efficacy, and precise indications in comparison with other sources of hematopoietic stem cells. The ethics of UCBT must properly respect the rights and needs of both donors and recipients.

A detailed analysis of charges for hematopoietic stem cell transplantation at a children's hospital.

We analyzed hospital charges for pediatric hematopoietic stem cell transplantation (HSCT) to understand better the medical origin of these charges. Forty-nine patients undergoing HSCT at Kosair Children's Hospital between January 1992 and August 1995 had hospital charges analyzed by cost center, donor type and clinical outcome. Thirty-three autologous, two syngeneic and 14 allogeneic transplants were performed. Twenty-four transplants were performed for hematological malignancies, 22 for solid tumors, and three for non-malignant diseases. Pharmaceutical charges comprised the largest single component of total hospital charges (THC), accounting for 38.9%. Room charges were the next largest group at 33.7% of THC. Other cost centers, in order of magnitude, were central supply (7.9%), transfusion services (7.5%), laboratory (5.8%), microbiology (3.6%), miscellaneous (1.9%), and radiology (1.4%). Within the pharmaceutical cost center, colony-stimulating factors comprised the largest single item, making up 18% of total pharmacy charges and 7% of THC. Antibiotics were the second largest component, at 16% of pharmacy charges and 6% of THC. Patients transferred to the intensive care unit (ICU) had charges 68% greater than non-ICU patients. Allogeneic transplant patients had THC 35% greater than autologous transplant patients, but also a four-fold greater chance of becoming an ICU patient. THC for non-ICU allogeneic transplant patients were 18% greater than for autologous non-ICU patients. THC for allogeneic ICU patients were 21% greater than for autologous ICU patients. Patients who died of transplant-related toxicity prior to day 100 had THC 83% greater than those who survived beyond day 100. This is the first published comprehensive and detailed analysis of charges associated with hematopoietic stem cell transplantation. With increased emphasis on the provision of cost-effective care in both Europe and the USA, medical practices must be examined with the goal of reducing inefficiencies while preserving quality of care. Understanding the genesis of charges in expensive procedures such as stem cell transplantation is an initial step in cost containment.

Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group.

PURPOSE: In a previous randomized trial, the addition of adjuvant chemotherapy to postoperative radiotherapy proved beneficial in the treatment of childhood high-grade astrocytomas. The present study tests the hypothesis that an eight-drug adjuvant chemotherapy regimen would improve survival in such children compared with the three-drug regimen of the prior study. PATIENTS AND METHODS: Between April 1985 and May 1990, patients between the ages of 18 months and 21 years with newly diagnosed high-grade astrocytomas were eligible for this study, as determined by the treating institution's histopathologic diagnosis. Treatment consisted of postoperative local-field radiotherapy and adjuvant chemotherapy, either lomustine (CCNU), vincristine, and prednisone (control regimen) or eight-drugs-in-1-day chemotherapy (experimental regimen). Two cycles of postoperative preirradiation chemotherapy were administered in the experimental regimen. Patients were evaluated radiographically every 3 months after irradiation. RESULTS: Eighty-five eligible patients were randomized to the control regimen and 87 to the experimental regimen. The progression-free survival (PFS) and overall survival (OS) at 5 years were 33% (SE = 5%) and 36% (SE = 6%), respectively. There was no statistical difference in outcome between the two chemotherapy regimens. In patients with confirmed diagnoses of anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM), anaplastic astrocytoma, greater than 90% resection, and nonmidline tumor location were characteristics predictive of an improved PFS. There was a difference in toxicity between the two chemotherapeutic regimens, with greater myelosuppression and hearing loss in the experimental regimen. Tumor recurrence occurred primarily within the primary tumor site. CONCLUSIONS: There is no benefit to the treatment of high-grade astrocytomas in children with eight-drugs-in-1-day chemotherapy compared with CCNU, vincristine, and prednisone. Extent of tumor resection and histopathologic diagnosis are significant prognostic variables. The overall outcome for children with high-grade astrocytomas remains poor.

Neonatal immune neutropenia following the administration of intravenous immune globulin.

BACKGROUND: In adults--but not neonates--neutropenia has been reported to complicate treatment with intravenous immunoglobulin, but the mechanism is unknown. PURPOSE: To describe for the first time the case of a newborn infant who, after intravenous immunoglobulin, demonstrated serum antineutrophil antibodies and neutropenia. PATIENTS AND METHODS: The 1,425-g, 36-week-gestation boy was healthy except for intrauterine growth retardation. Intravenous immunoglobulin (1g/dose x 3) was administered to treat alloimmune thrombocytopenia. Neutrophil-specific antibodies were detected by a granulocyte immunofluorescence assay. RESULTS: After the intravenous immunoglobulin, the platelet count normalized but the neutrophil count declined to 450/mm3. Neutrophil-specific antibodies were detected in the serum of the infant but not in the maternal serum. Furthermore, cross-matching revealed that the maternal serum did not react with the infant's granulocytes. Two of three random lots of intravenous immunoglobulin contained detectible anti-neutrophil antibodies. CONCLUSIONS: After intravenous immunoglobulin, the infant's serum contained one or more anti-neutrophil antibodies that were not maternal in origin. We speculate that the neutropenia resulted from the administration of intravenous immunoglobulin containing antineutrophil antibodies.

Risk of malignancy in Sotos syndrome.

A questionnaire survey identified a possibly increased risk of malignancy for patients with Sotos syndrome. Because the sites and types of neoplasm found in these patients vary, no routine screening except for periodic clinical evaluation seems feasible.

Hb Mizuho or alpha 2 beta (2)68(E12)Leu----Pro in a Caucasian boy with high levels of Hb F; identification by sequencing of amplified DNA.

Hb Mizuho, an unstable beta chain variant with a Leu----Pro substitution at position beta 68, was observed in a young Caucasian boy from Kentucky. Identification was made by sequence analyses of amplified DNA and by hybridization of amplified DNA with specific probes. The patient had high Hb F levels up to the present age of nearly 5 years; this high Hb F might in part be responsible for his condition which was considerably milder than that seen in the two patients described in earlier reports. The increased gamma chain synthesis may be due to special characteristics of the beta-globin gene cistron which are comparable to those observed in sickle cell anemia patients with a relatively mild disease.

A phase II study of cisplatin therapy in recurrent childhood brain tumors. A report from the Childrens Cancer Study Group.

Thirty-six children with brain tumors were treated with surgery, radiation and/or adjuvant chemotherapy. After tumor recurrence, cisplatin (60 mg/m2/day IV X 2) was given every three to four weeks. CT scans were used to measure drug response prior to the first, third and fifth courses. Complete and partial responses were demonstrated in nine of 31 evaluable patients. Dose limiting toxicities were renal and auditory. Seven patients developed the syndrome of inappropriate antidiuretic hormone secretion. This study confirms that cisplatin is active in a spectrum of brain tumors.

Budd-Chiari syndrome secondary to hepatic vein thrombus from Wilm's tumor. Case report and literature review.

We describe a case of Budd-Chiari Syndrome in a 6-year-old boy secondary to Wilm's tumor. The patient had a right nephrectomy and mediastinotomy with removal of the tumor from the right atrium, inferior vena cava, and hepatic vein. Postoperatively, the patient had chemotherapy consisting of Actinomycin-D to be followed by radiation to the tumor bed to a total dose of 2000 rads in 10 fractions by using AP/PA field on 6 MeV Linear Accelerator. Currently, the child is receiving combination chemotherapy.

Intracardiac extension of Wilms' tumor.

Three cases of right-sided Wilms' tumor with direct intracardiac extension are described. Wilms' tumor is one of the most common intraabdominal tumors of childhood. Primary cardiac tumors that arise from myocardium are extremely rare. Metastasis to the heart or pericardium is usually a late complication in the course of a malignancy. In Wilms' tumor cardiac manifestations may be the presenting symptoms at the time of diagnosis. The prognosis for Wilms' tumor with intracardiac extension of the tumor is poor. A thorough cardiovascular examination and a metastatic workup should be done for abdominal masses presumptive of Wilms' tumor. Two-dimensional echocardiography is a noninvasive diagnostic tool, and the information obtained by its use not only allows planning of surgical intervention, chemotherapy, or local radiation therapy, but also is beneficial for long-term follow-up. Aggressive surgery, chemotherapy, and radiation therapy has increased the survival figures of these children.

Hemoglobin E: another cause of microcytic anemia in North America.

The influx of Southeast Asians has expanded the differential diagnosis of microcytic, hypochromic anemia in this country. We describe four patients with hemoglobin E, all of whom had microcytic, hypochromic anemia. Hemoglobin E is benign in both the heterozygous and homozygous states. On routine hemoglobin electrophoresis at pH 8.4, hemoglobin E will migrate near the hemoglobin C and hemoglobin A2 regions. If hemoglobin E is suspected, the laboratory should be advised to do electrophoresis on citrate agar at pH 6.3.

Acute psychosis complicating induction therapy for acute lymphoblastic leukemia.

Two adolescents with acute lymphoblastic leukemia developed acute psychotic episodes shortly after induction therapy, which included prednisone, was begun. Symptoms included regressive behavior, incontinence, fluctuating levels of activity, and delusions. Both patients regained normal mental status after a number of weeks. Treatment included tapering of steroid dosage, introduction of a highly structured environment, and early use of chlorpromazine. Psychosis persisted beyond discontinuation of steroid therapy, but both patients subsequently received steroids after return of normal mentation, and in neither did psychosis recur.

Delayed pancreatic pseudocyst formations. Long-term complication of L-asparaginase treatment.

L-asparaginase-induced pancreatitis has been reported during or closely following administration of the drug. Three cases of pseudocyst of the pancreas in two women and one man have previously been reported with the use of intravenous L-asparaginase. An adolescent male developed acute pancreatitis and pseudocyst of the pancreas 16 weeks after cessation of intramuscular L-asparaginase. Delayed pseudocyst of the pancreas can be a complication of intramuscular L-asparaginase.

Plasma phenylalanine: tyrosine ratios during high-dose methotrexate-citrovorum "rescue".

We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CV. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.