Subacute central nervous system degeneration in a child: an unusual manifestation of ifosfamide intoxication.

A 5-year-old child with desmoplastic small round-cell tumor was treated with a protocol of very-high-dose, short-term chemotherapy, containing HD-CAV (cyclophosphamide, doxorubicin, vincristine, and mesna), ifosfamide, and etoposide. Two days after the initiation of ifosfamide, he exhibited new-onset lethal encephalopathy manifested by subacutely progressive cerebellar and then temporal and frontocortical degeneration leading to a vegetative state and eventually to death. A full work-up, including brain biopsy, was negative, excluding infections and metabolic or vascular causes. Ifosfamide is known to be capable of causing acute encephalopathy that can be severe but is generally reversible. This child showed a very atypical progressive, lethal course of ifosfamide toxicity. The possibility of this complication should be considered when high-dose ifosfamide treatment is planned for children.

The pattern of bone disease in transfusion-dependent thalassemia major patients.

Twenty-eight patients with thalassemia major were treated with frequent blood transfusions for 10-25 years. Eleven (39%) had radiographic signs of osteoporosis, and four (14%) presented with fractures. Keeping hemoglobin level above 9.0 g/dl reduced osteoporosis and the incidence of fractures but did not prevent them. Osteonecrosis of the femoral head and distal femur, not previously reported, was noted in two patients.

Peripheral blood stem cells as a source for hemopoietic recovery following autologous bone marrow transplantation in childhood malignancy.

In an attempt to improve hemopoietic recovery after autologous bone marrow transplantation (ABMT), a project of peripheral blood stem cells (PBSC) harvest was initiated. Thirty-six children awaiting ABMT underwent 126 PBSC harvests primed by a conventional scheduled chemotherapy course and rGMCSF 5 micrograms/kg per day/s.c. Ages ranged from 12 months to 19 years and weight from 9 to 84 kg. PBSC harvest was carried out using the Fenwall CS 3000 Plus with the small volume collection chamber at a maximum whole blood flow rate of 15-45 ml/min; total volume processed was 1,700-10,000 ml. Total nucleated cells per collection was 0.35-5.62 x 10(8) cells per kg, and the number of CD34+ cells, 0.23-1.1 x 10(6)/kg. The number of colony forming units-granulocyte macrophages (CFU-GM) varied in these heavily pretreated patients from 0 to 5.3 CFU-GM x 10(4)/kg per collection. Immunophenotyping of the cells collected was performed by double staining for CD34, CD33, CD15, CD71, Ia and CD56. Most of the CD34+ cells were found to be CD38+; some were CD33+ and some CD33-. Low coexpression of CD34+ CD71+ cells may correlate with the low proliferating capacity of PBSC as compared to the BM cells. To date 22 children have undergone transplantation using combined autologous PBSC and bone marrow. We conclude that PBSC harvest is a feasible and safe procedure even in small children, and can be successfully performed following scheduled chemotherapy and administration of growth factors, resulting in substantial yield, also in heavily pretreated patients. This procedure is recommended in responding high risk patients at the stage of minimal residual disease and may replace ABMT in the future.

Ambulatory treatment with ceftriaxone in febrile neutropenic children.

We conducted a prospective nonrandomized study of outpatient therapy with ceftriaxone as a single agent in 50 episodes of fever and neutropenia in children treated with various myelosuppressive regimens for different malignancies. All patients underwent clinical and radiological evaluation and blood/urine cultures taken before starting therapy. Patients with dehydration, hypotension, rigor and clinical exit-site infection of indwelling right-sided catheters were excluded. Forty-one patients completed an antibiotic course of 7 days: in 12 patients fever returned to normal on day 2, in 10 patients on day 3, and in 8 patients on day 4. The duration of neutropenia following the initial febrile episode was 3-10 days. In some patients fever returned to normal after 2 days, but neutropenia persisted up to 10 days. Two patients were bacteremic--Escherichia coli in one, and Acinetobacter/Staphylococcus coagulase negative in another; all isolates were sensitive to ceftriaxone. In nine episodes, antimicrobial therapy was modified because of persistent fever > 39 degrees C in five patients, bacteremia in two, enterocolitis in one, breakthrough fever in two, and bronchopneumonia in one. The low incidence of bacterial isolation is probably attributed to the selection of patients with low risk features. Patients and parents complied with and favored outpatient therapy to hospitalization.

Long-term intravenous deferoxamine treatment for noncompliant transfusion-dependent beta-thalassemia patients.

With the introduction of long-term subcutaneous administration of deferoxamine (DFO), there has been a decline in the morbidity and mortality of transfusion-dependent beta-thalassemia patients. However, since the use of subcutaneous DFO is hindered by poor compliance, long-term i.v. DFO therapy has been attempted in order to improve compliance, prevent excessive iron accumulation and extend survival. Thirteen patients (aged 5.4-18.4 years) were started on i.v. home administration of DFO (100 mg/kg per day) via an exteriorized, tunneled right atrial catheter (Hickman type). After a median follow-up of 36 months, the mean ferritin levels had dropped significantly (5,117 +/- 1,737 to 1,816 +/- 1,062 micrograms/l. P = 0.0001). None of the patients developed new endocrine or cardiac diseases due to iron overload. Patients beginning therapy at an early age (< or = 11 years) showed a tendency for improved growth parameters at the end of the treatment period. Two patients developed moderately high frequency sensorineural hearing loss. One patient developed a right atrial thrombus. The line infection rate was low (1.7 episodes per 1,000 patients days). In view of the grave prognosis for iron overloaded patients and the fact that oral chelators are not yet readily available, we recommend this form of therapy for the young, noncompliant beta-thalassemia patient, despite the occasional complications observed.

Genetic alterations involving chromosome 1p in children with neuroblastoma.

Neuroblastoma is a common childhood tumor of the sympathetic nervous system, characterized by N-myc amplification and loss of heterozygosity (LOH) for sequences on chromosomes 1p, 11q and 14q. Using restriction fragment length polymorphism analysis, the constitutional and tumor genotypes were compared for LOH on 1p in 25 children with neuroblastoma at diagnosis: 19 in stages III-IV, 5 in stages I-II and one in IVs. The genetic alterations observed on chromosome 1p were frequent in the early and advanced stages. Thirty-three percent of the alterations were found in patients under the age of 1 year, and in one patient with IVs. It is concluded that 1p alterations were identified in children with neuroblastoma in early stages and infants and thus of no prognostic relevance. 1p genetic alterations may be early events in neuroblastoma.

The use of two alpha blocking agents, phenoxybenzamine and phentolamine, in ointment and injection form to improve skin flap survival in rats.

Two alpha blocking agents, phenoxybenzamine and phentolamine, were tested to see if their use improved skin flap survival in rats. The agents were used in two ways: in local injections and topical applications. The results showed an increased duration of flap viability with both modalities, but the topical application was the most effective.