Lawrence S. Frankel

Treatment of Hepatosplenic Candidiasis With Liposomal-Amphotericin B

Nine patients with hematologic malignancies developed fungal infections, predominantly involving the liver and spleen. Eight patients had biopsy-documented progressive candidiasis and one had an unclassified fungus. The patients were treated with liposomal-amphotericin B (L-AmpB) after their fungal infection progressed during treatment with standard intravenous (IV) AmpB (Fungizone; E. R. Squibb & Son, Princeton, NJ) and/or other antifungals. Eight patients (88.8%) were cured of their fungal infection, and one showed improvement after treatment. Minor acute toxicity and no chronic toxicity were associated with the administration of L-AmpB. L-AmpB is a safe and effective therapeutic method for treating fungal infections that have invaded the liver and spleen even when they are refractory to conventional anti-fungal therapy.

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 lymphocytic 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 had 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.

Alprazolam in the Treatment of Anticipatory and Acute Situational Anxiety in Children with Cancer

Abstract A population of childhood cancer patients who undergo scheduled, periodic, stressful events such as bone marrow aspirations and spinal taps was chosen as a model for the investigation of the use of alprazolam in the treatment of anticipatory and acute situational anxiety in children. An open-label dose-ranging study was completed on 13 children. Because this was an early trial of a drug not approved for use in children, doses were low. Nonetheless, safe efficacious use of alprazolam was demonstrated and indicates that antianxiety agents may have a useful purpose for brief intervention situations in children.

Ethnicity and cure rates of Texas children with acute lymphoid leukemia

Ethnic differences in the survival of children treated for acute lymphoid leukemia (ALL) have been described in several locations. Children of African, Polynesian, Native American, and Mexican ancestry had a less favorable outcome than children of European ancestry when treated in a similar manner by the same physicians and nurses.

Evaluation of AMSA in children with acute leukemia. A pediatric oncology group study

One hundred four children with advanced leukemia in relapse (74 with acute lymphocytic leukemia [ALL] and 30 with acute nonlymphocytic leukemia [ANLL]) received AMSA (4′‐(9‐Acridinylamino)methanesulfon‐m‐anisidide) at a dose of 120 mg/m2/day for 5 days (Regimen I) or 60 mg/m2/day for 10 days (Regimen II). Children with ALL were randomized between Regimens I and II (31 and 36 evaluable patients, respectively). All 29 evaluable patients with ANLL were treated on Regimen I. Eighty‐eight percent of evaluable patients experienced severe or life‐threatening toxicity, with no statistical differences between Regimens I and II. Bacterial or fungal infections (considered life‐threatening or fatal) occurred in 17 children with ALL and in 7 with ANLL. Fatal cardiac toxicity occurred in one patient. Complete or partial response occurred in 25.0% (SE = 8.8%), 28.1% (SE = 8.0%), and 25.9% (SE = 8.4%) of evaluable patients on ALL Regimen I, ALL Regimen II, and ANLL, respectively. However, responses were of short duration (16–91 days). There was no significant difference in the duration of survival from treatment start for the two ALL regimens (P = 0.46). The median duration of survival for ANLL patients was significantly longer (P = 0.004) than that of ALL patients treated on Regimens I and II combined. Eighty‐two percent of the complete or partial responses (18 of 22) occurred after the first course of AMSA. At the dose schedules investigated, and in a heavily pretreated patient population, AMSA had activity in childhood leukemia. However, the high incidence of severe, life‐threatening, or fatal infections meant that the quality and quantity of responses and survival was not commensurate with the toxicity, and that it would be difficult to incorporate this drug into combination chemotherapy with other myelosuppressive agents.

Antimicrobial therapy of febrile children with malignancies and possible sepsis

A prospective study of 100 pediatric patients (2 months to 17 years of age) who had malignancies and fever was conducted. Gentamicin or netilmicin and a beta-lactam antibiotic were administered as initial empiric treatment. Be-fore therapy profound granulocytopenia (fewer than 500 polymorphonuclear leukocytes/μl) was present in 66% of children and persisted to the end of therapy in 42% of children. Of the 40 children with microbiologically documented infections, 38 (95%) responded to therapy. The aminoglycoside dosing regimen of 2 mg/kg/dose intravenously over 60 minutes every 6 hours produced antibiotic concentrations in serum of 5.8 ± 0.3 μg/ml at the end of the infusion in the netilmicin group and 1.5 ± 0.1 μg/ml 6 hours after the infusion and of 6.2 ± 0.2 and 0.9 1 0.1 μg/ml for the two time periods in the gentamicin group. The serum half-lives, volumes of distribution and the total body clearance rates were comparable for netilmicin and gentamicin. No accumulation of netilmicin or gentamicin was noted. Seven patients had renal compromise, five before institution of antibiotic therapy and two while on therapy. Four episodes of ototoxicity were not related to antibiotic therapy. Superinfection occurred in five children. The combination of either gentamicin or netilmicin with a beta-lactam antibiotic produced excellent results for episodes of fever in neutropenic children with cancer. In children with severe underlying disease and/or granulocytopenia, anti-biotic combinations have achieved an optimal efficacy. Future emphasis should be placed on prevention, immunoregulation and nonbacterial pathogens.

Rubidazone in the treatment of recurrent acute leukemia in children: a pediatric oncology group study

This study tested the efficacy of rubidazone in the treatment of recurrent acute leukemia in children. In the first phase of this study, rubidazone was administered in a dose of 450 mg/m2 to 26 children with acute lymphocyte leukemia (ALL) and to 8 children with acute nonlymphocytic leukemia (ANLL) in relapse. In children with ALL, 6 patients (23%) achieved a complete remission (CR) and an additional 4 patients (15%) achieved a partial remission (PR). Of 8 children with ANLL, 2 (25%) achieved a CR, and an additional patient achieved a PR. Because of the moderate to severe toxicity of rubidazone, the next phase of the study consisted of randomizing patients between a dose of 450mg/m2 and 300 mg/m2 of rubidazone. In children with ALL in their first relapse who were not resistant to Adriamycin (doxorubicin), 7 of 10 patients (70%) achieved a CR with 450 mg/m2 of rubidazone, whereas 2 of 12 patients (17%), achieved a CR with 300 mg/m2 (P < 0.04). In children with ALL in their first relapse but resistant to Adriamycin, 3 of 17 patients (18%) achieved a CR with 450 mg/m2, and 2 of 17 patients (12%), achieved a CR with 300 mg/m2. This study suggests that rubidazone is capable of inducing remission in children with ALL in relapse. The main toxicity of rubidazone consisted of severe and prolonged myelosuppression resulting in fever and infection. This toxicity was not significantly decreased by reducing the dose of rubidazone from 450 mg/m2 to 300 mg/m2. Fatal cardiac toxicity was observed in 3 children. Cancer 57:1461–1463, 1986.