Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children's Oncology Group.

Mucositis can be a serious complication of hematopoietic SCT (HSCT). A previous phase II trial in 32 children undergoing HSCT reported a beneficial effect of the homeopathic remedy Traumeel S. The Children's Oncology Group sought to replicate the results in a multi-institutional trial. The study was an international multi-center, double-blind, randomized trial comparing Traumeel with placebo in patients aged 3-25 years undergoing myeloablative HSCT. Traumeel/placebo was started on Day -1 as a five-time daily mouth rinse. Efficacy of the treatment was assessed using the modified Walsh scale for mucositis, scored daily from Day -1 to 20 days after HCST. The main outcome was the sum of Walsh scale scores (area-under-the-curve (AUC)) over this period. Other outcomes included narcotic use, days of total parenteral feeding, days of nasogastric feeding and adverse events. In 181 evaluable patients, there was no statistical difference in mucositis (AUC) in the Traumeel group (76.7) compared with placebo (67.3) (P=0.13). There was a trend towards less narcotic usage in the Traumeel patients. No statistically beneficial effect from Traumeel was demonstrated for mucositis. We could not confirm that Traumeel is an effective treatment for mucositis in children undergoing HSCT.

A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study.

Severe mucositis is a common cause of morbidity in hematopoietic stem cell transplant (HSCT) recipients. Glutamine has been shown to reduce mucositis in children receiving chemotherapy. Patients were randomized in a double-blind manner to receive glutamine or glycine at a dose of 2 g/m(2)/dose (maximum dose 4 g) twice daily until 28 days post transplant or discharge if sooner. Mucositis was graded by use of a modified Walsh scale. A total of 120 children were evaluable: 57 children received glutamine and 63 received glycine. The mean mucositis score was 3.0+/-0.3 vs 3.9+/-0.4 (P=0.07) in the glutamine and glycine groups, respectively. The glutamine group demonstrated a reduction in mean number of days of intravenous narcotics use (12.1+/-1.5 vs 19.3+/-2.8 in the glycine group, P=0.03) and total parenteral nutrition (17.3+/-1.7 vs 27.3+/-3.6 in glycine group, P=0.01). There was no statistically significant difference in toxicity between the two groups. Glutamine appears to be safe and beneficial in reducing the severity of mucositis. Strong consideration should be given to include oral glutamine supplementation as a routine part of supportive care of SCT patients.

Psychosocial supportive care for children receiving stem cell transplantation: practice patterns across centers.

Although pediatric stem cell transplantation is associated with elevated risks for quality-of-life (QOL) deficits, morbidity, and late effects, little is known about how supportive care needs are addressed across different pediatric centers. This study examined practice patterns among centers enrolled in the Pediatric Blood and Marrow Transplant Consortium. In all, 65 centers (response rate=82.2%) were surveyed regarding QOL screening, psychosocial intervention services, and long-term follow-up care. Approximately 80% of centers provided routine screening for psychological difficulties and pain. A smaller number screened for fatigue (69.2%), cognitive deficits (52.3%), sleep difficulties (60.0%) or spiritual concerns (38.5%). Screening was conducted predominantly via interview; little use was made of standardized measures. Community-based centers screened some deficits more frequently than did academic ones (all P's

Infections in children with cancer: a continued need for the comprehensive physical examination.

Few studies have addressed the influence of profound myelosuppressive therapy in contemporary protocols on infectious morbidity in pediatric oncology patients. This study evaluates the types of infections and the methods used to diagnose infection in patients enrolled in current Children's Cancer Group (CCG) protocols. Data were collected on patients enrolled in CCG protocols from January 1, 1992, through December 31, 1995. Of the 155 protocol patients, 102 were completely evaluated and had data collected through August 1, 1996. Patients were divided into two diagnosis groups: leukemia/lymphoma (N = 51) and solid tumor (N = 51). Eighty-five (83%) patients had documented infections and 17 (17%) did not. Overall, 96 (94%) patients had in-dwelling central venous catheters. Twelve categories of infection were identified. Data were analyzed for age, gender, diagnosis, neutropenia, organism, and disease state (primary active, recurrent active, primary remission, and secondary remission). Statistical comparisons were made only on rates, whereas descriptive comparisons were given for numbers of infections and organisms. The infection rates for patients with active disease were 1.01 and 1.15 per 100 patient days (primary versus recurrent) and 0.59 and 0.38 per 100 patient days for patients with disease in remission (primary versus secondary). Diagnosis-group infection rates were 0.66 and 0.68 per 100 patient days for patients with solid tumors and leukemia/lymphoma, respectively. Three hundred thirty infections, including 19 polymicrobial infections, were recorded. The three most common types of infection were otitis media, septicemia, and urinary tract infection. More infections were associated with an age at diagnosis of less than 3 years, a leukemia/lymphoma diagnosis in remission, and an absolute neutrophil count >500 cells/microL. One hundred ninety-four organisms were isolated from 330 infections. Gram-positive organisms (n = 74) such as coagulase-negative Staphylococci (n = 38) predominated over gram-negative organisms (n = 63) for all infectious categories. Specifically, gram-positive organisms (n = 39) were isolated more often from blood cultures than were gram-negative organisms (n = 27). The overall mortality for patients was 36%. Seven of the 37 (19%) patient deaths were attributed to infection. These patients predominantly were girls with neutropenia and leukemia/ lymphoma in active disease who died of gram-negative sepsis. Infections with gram-positive organisms continue to be major causes of morbidity in pediatric oncology patients receiving contemporary CCG protocols. However, infection-related mortality, especially with gram-negative organisms, occurs less frequently than does malignancy-related mortality. Common childhood infections (such as otitis media) seem equally as prevalent as bacteremia in pediatric oncology patients. Thus, a comprehensive physical examination is as imperative as the microbiologic evaluation in diagnosing infection in this patient population.

Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients.

PURPOSE: To compare the efficacy, characteristics of onset/recovery, and safety of ketamine/atropine/midazolam with meperidine/midazolam used as premedication for painful procedures in children with cancer. METHODS: A randomized, double-blind crossover trial for two successive painful procedures (bone marrow aspiration or biopsy, lumbar puncture, or combined procedures) was performed at a referral-based pediatric hematology-oncology clinic and associated inpatient service of a university teaching hospital. Twenty-two children, aged 24 to 178 months, were enrolled and 18 (81.8%) completed the double-blind, crossover trial. Each child received intravenous premedication with either meperidine 2 mg/kg and midazolam 0.1 mg/kg (MM) or atropine 0.01 mg/kg, midazolam 0.05 mg/kg, and ketamine 1.5 mg/kg (KM) on one occasion followed by the alternative regimen on a second occasion. The initial premedication regimen was chosen by random assignment. RESULTS: Efficacy was assessed by a trained observer using the Observational Scale of Behavioral Distress-Revised (OSBD-R). Operator, nurse, parent, and patient opinions of efficacy were recorded on a visual analog scale (VAS). Side effects were monitored by pulse oximetry, nasal end-tidal capnography, and serial blood pressure measurements. Use of KM resulted in significantly less procedural distress than MM (1.37 +/- 2.20 v 7.04 +/- 8.06 OSBD-R units; P < .05). Both operators and nurses rated KM more effective than MM. KM use was associated with earlier readiness for the procedure (19.2 v 24.0 minutes) and more rapid recovery (39.3 v 74.6 minutes for removal of monitoring devices and 58.5 v 87.1 minutes for discharge). Procedures undertaken after ketamine sedation were associated with fewer side effects than observed with MM sedation (hypoxia, 17.7% v 82.4%; hypotension, 16.6% v 55.6%; reduced respiratory rate, 0% v 38.9%). The incidence of emergence reactions or behavioral abnormalities within 24 hours postprocedure was similar in both treatment groups. At 7 days postprocedure, no child had persistent behavioral abnormalities and all children had amnesia for the procedure. Parents and children expressed a preference for KM over MM in 12 of 18 cases (P < .05). CONCLUSION: A premedication regimen of KM produced superior sedation with a faster onset and recovery and fewer side effects than a MM combination.

Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine.

PURPOSE: We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. PATIENTS AND METHODS: Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles. Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF. A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. RESULTS: SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients. There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and an independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. CONCLUSION: Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine -- the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose.

Recent developments in the management of neuroblastoma.

Neuroblastoma was first described in 1864 by Virchow. For the next 100 years, the primary approach to these patients was predominantly surgical resection. With the advent of multimodal adjuvant treatments using chemotherapy and irradiation in the 1950s and 1960s, coordination of multispecialty therapeutic interventions became important. By the late 1970s, effective neoadjuvant chemotherapeutic regimens enabled some inoperable tumors to be completely removed at the time of "second look" procedures. In the 1980s, advances in tumor biology and imaging gave new insight and novel prognostic indicators which helped determine the course of therapy. In the 1990s, treating poor risk patients with extremely high dose chemotherapy, irradiation, and allogeneic or autologous bone marrow rescue with or without surgical resection may finally improve the survival of these children.

Single copies of the N-myc oncogene in neuroblastomas from children presenting with the syndrome of opsoclonus-myoclonus.

Patients with neuroblastoma who present with the syndrome of opsoclonus and myoclonus enjoy a remarkably good prognosis independent of their stage of disease or their age at diagnosis. The presence of N-myc amplification also has been found to be an independent prognostic factor in neuroblastoma. Patients with multicopy N-myc tumors have rapid tumor progression whereas those with single-copy tumors have a significantly better progression-free survival. The authors examined four primary, untreated neuroblastomas for the N-myc copy number from patients who presented with opsoclonus and myoclonus. All four tumors had single copies of N-myc, and all four patients are alive with no evidence of recurrent disease with 6+ to 54+ months' follow-up. This appears to be the only report of N-myc analysis in this group of children. It would be interesting to analyze more neuroblastomas from patients who present with opsoclonus and myoclonus to determine how many of these patients have single N-myc copy tumors.

The effect of aging on sister chromatid exchange.

The advent of the bromodeoxyuridine(BrdU)-differential staining techniques has greatly facilitated the detection of sister chromatid exchanges (SCE). These SCE have been demonstrated to be an accurate reflection of DNA damage both in vitro in cultured cells and in vivo in mouse and rate bone marrow and spleen cells. In this review, we examine the effect of cellular aging on both baseline and mutagen-induced SCE levels. In all systems examined, aging did not appear to significantly affect the baseline levels of SCE. However, in human fibroblast cultures we have found a significant decrease in the levels of mutagen-induced SCE as a function of both in vitro passage level (in vitro aging) and the age of the cell culture donor (in vivo aging). In addition we have found a similar decrease in mutagen-induced SCE levels in both mouse and rat bone marrow cells and mouse spleen cells where examinations were performed entirely in vivo. Diminished mutagen-induced SCE levels were obtained with a wide variety of agents including mitomycin-C, cyclophosphamide, adriamycin, ethyl methanesulfonate and N-acetyl-2-acetoxyamino-fluorene. These decreased SCE levels were accompanied by increased frequencies of chromosomal aberrations in the older cell populations. If SCE represents a form of DNA repair as has been suggested by several investigators, our finding would indicate impaired DNA repair occurring in old cells.