Marilyn H. Duncan

Age‐linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the pediatric oncology group

Histologic sections (minimum of four sections per patient) from 211 patients with neuroblastoma were reviewed. The tumors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (≤ ten per ten high‐power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log‐rank tests (P < 0. 0001 and P = 0. 0065, respectively). Histologic Grades 1, 2, and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had absence of low MR, i.e., these tumors had high MR [> ten per ten high‐power fields]). Statistically significant differences in survival were observed in the grades after adjusting for age and stage (P < 0. 001). The degree of differentiation, although significant by itself, was no longer significant after adjusting for the grades, Age groups (≤ 1 versus > 1 year of age), which also emerged as an independent prognostic feature (P < 0. 001), were linked with the grades to define two risk groups as follows: (1) a low‐risk (LR) group consisting of patients in both age groups with Grade 1 tumors and patients 1 year of age or younger with Grade 2 tumors and (2) a high‐risk (HR) group consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statistically significant (P < 0. 001). Concordance between these LR and HR groups and the Shimada classification was observed in 84% of cases. The new histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested on a new data set with an appropriate histologic sample of similar size to confirm these results.

Assessment of Chemotherapy-Induced Emesis and Evaluation of a Reduced-Dose Intravenous Ondansetron Regimen in Pediatric Outpatients with Leukemia

Objective: To measure the severity of nausea and vomiting in pediatric patients receiving intravenous or intrathecal chemotherapy for acute lymphoblastic leukemia and to evaluate the effectiveness of 2 intravenous doses of ondansetron for this condition. Design: Patients were surveyed during repeated treatments of maintenance chemotherapy, given with or without ondansetron, using a repeated measures pretest/posttest design. Setting: Outpatient pediatric oncology clinic. Patient population: Sixteen pediatric patients (aged 2–15 years, mean 6.2) with acute lymphoblastic leukemia. Methods: Surveys to assess nausea and vomiting and the extent of interference with daily activities were administered following emetogenic chemotherapy with or without ondansetron. Results: A total of 255 surveys following emetogenic chemotherapy with daunorubicin, cyclophosphamide, carmustine, and etoposide and cytarabine combined, as well as intrathecal therapy with methotrexate, hydrocortisone, and cytarabine, were analyzed. Analysis was performed on surveys of 149 courses without antiemetic therapy and 106 courses after 2 doses of ondansetron 0.15 mg/kg iv. The most emetogenic chemotherapy treatment was the etoposide/cytarabine combination (p<0.05). Ondansetron completely protected patients (defined as no nausea or no vomiting) during most (>50%) of the chemotherapy treatments, except for those in which cyclophosphamide was used. Ondansetron provided greater control of nausea and vomiting, a higher percentage of complete protection, and decreased the daily activity interference rating for carmustine and etoposide/cytarabine compared with courses of chemotherapy without antiemetics (p<0.05). Two intravenous doses of ondansetron also provided durable antiemetic efficacy over time for the most emetogenic chemotherapy treatment (etoposide/cytarabine). Conclusions: Etoposide/cytarabine proved to be the most emetogenic of the chemotherapy treatments studied. A reduced-dose regimen of intravenous ondansetron was shown to be an effective antiemetic for the outpatient treatments with etoposide/cytarabine and carmustine, but not with cyclophosphamide.

Rhizopus osteomyelitis. A case report and review.

Mucormycosis osteomyelitis has previously been described exclusively in association with contiguous infections of rhinocerebral mucormycosis. In a patient with corticosteroid-dependent neutropenia and anemia osteomyelitis of the femur developed caused by the Mucoraceae Rhizopus. Although a primary focus was not identified, we believe this infection was hematogenous in origin. Mitogen stimulation to phytohemagglutinin (PHA) of the patients lymphocytes revealed depressed cellullar immunity; however, there was specific response to Rhizopus extract. Treatment with systemic amphotericin B prevented further progression of the infection. A review of mucormycosis osteomyelitis is presented.

Continuous Midazolam Infusion for the Management of Morphine-Induced Myoclonus

Objective: To describe a patient with morphine-induced myoclonus treated with a continuous infusion of midazolam and continued morphine dose escalation. Design: Single case report. Setting: Delivery, monitoring, and titration of morphine and midazolam in the patients home by a homecare agency. Results: The use of high dosages of morphine (i.e., 500 mg/h) produced myoclonic spasms in this patient, which in turn resulted in increasing pain. To allow for continuation of effective analgesia and to control the myoclonic spasms, an infusion of midazolam was initiated and titrated. The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation. As morphine dosages were further escalated, it was also necessary to increase the midazolam infusion to control additional myoclonic spasms. Conclusions: Use of a concomitant midazolam infusion with high doses of morphine appears to be safe and is an effective means of controlling morphine-induced myoclonus. If further dosage increases of morphine are necessary in this setting, increases in the midazolam infusion also may be required.

Economic impact with home delivery of chemotherapy to pediatric oncology patients

Objective To examine the economic impact of a home chemotherapy program (HCP) for pediatric oncology patients. Rationale Factors that led to initiation of an HCP included availability of specially trained nurses and programmable ambulatory infusion devices at local home care agencies, routine central venous catheter placement, inpatient bed space shortages, and the availability of ondansetron. Setting Chemotherapy delivery in the home setting from June 1991 through June 1994. Design Charge data and nausea and vomiting severity data were collected for patients treated through the HCP. Methods Economic impact was calculated by incorporating and summing all charge categories associated with hospital admission for chemotherapy (HAC) versus delivery by the HCP. All data were adjusted for 1993 dollars, and reflect charges for the average patient size (1 m2). Charge data for each chemotherapy protocol delivered in the home were analyzed by calculating the differences between HAC and HCP charges using the following formula: charge difference (HAC - HCP) per protocol times the number of courses. Total economic impact was calculated by summing the differences in charges for each protocol. Results A total of 262 chemotherapy courses were given to 44 patients (mean age 9.5 ± 5.1 y) through the HCP, which represented 1012 patient care days and 24 different chemotherapy protocols. Monetary savings from the HCP ranged from

Do random (non-clonal) chromosome abnormalities in bone marrow predict a clone to come ?

5180 per course of ifosfamide plus etoposide to

Differences among raters evaluating the success of EMLA cream in alleviating procedure-related pain in children with cancer.

367 per course for high-dose methotrexate. Total monetary savings from the HCP during the 3-year period was

Evaluation of a Skin Test for Chicken Pox

640 793. Successful control of nausea and vomiting with a combination of ondansetron plus methylprednisolone was achieved in approximately 80% of the patients receiving highly emetogenic chemotherapy protocols. Conclusions HCP for pediatric oncology patients results in substantial monetary savings to payors. Effective control of nausea and vomiting can be accomplished at home in the majority of patients with an ondansetron-based antiemetic regimen.

Childhood Ki-1 lymphoma : presentation as a buttock mass

The biologic significance of clonal karyotypic abnormalities in human neoplasms is becoming better understood, but the significance of rare chromosomal aberrations is uncertain. Useful, yet arbitrary, cytogenetic definitions of a clone have been established and cases with a frequency of chromosome aberrations less than the accepted convention are explained by random loss, karyotypic instability/evolution, or other technical artifact. Are non-clonal chromosomal abnormalities that may predict future clinically significant clones being ignored? A brief case report is presented raising two such issues in the same myelodysplastic patient. This child had monosomy 7 and, later, trisomy 8, as well as increased numerical/structural aberrations seeming to predict relapse. Preliminary data from the Southwestern Oncology group is also presented. Non-clonal data should be included, when appropriate, in the clinical report.

Visual and Verbal Short-Term Memory Deficits in Childhood Leukemia Survivors After Intrathecal Chemotheraphy

We evaluated the analgesic efficacy of EMLA cream after repeated bone marrow aspirations or lumbar punctures (LPs) in children with cancer, and compared the ratings among patients, their parents, physicians, and nurses. Data from LPs were analyzed at the last procedure without EMLA (T1) and the first and last procedures with EMLA (T2 and T3). Friedmans nonparametric analysis of variance was used for statistical analysis. A total of 272 procedures in 29 children were analyzed. For 179 procedures without EMLA, physicians rated pain lower than other raters, and for the 93 with EMLA physicians rated pain less than the children. Children rated pain at T2 lower than at T1 or T3. Physicians rated pain at T2 less than at T3. Both children and physicians rated pain at T3 as not different from that at T1. No differences were noted at these time points for other raters in LP distress ratings, or in bone marrow aspiration pain or distress ratings. Thus EMLA was associated with decreased pain ratings for LPs, but this effect was not sustainable with repeated procedures. The cream alone should not be relied on to control pain of bone marrow aspiration or repeated LPs in children. Physicians underestimated pain, which may have implications for undertreatment in this patient population.