Enhanced Risk Stratification for Children and Young Adults with B-Cell Acute Lymphoblastic Leukemia: A Children's Oncology Group Report.

Current strategies to treat pediatric acute lymphoblastic leukemia rely on risk stratification algorithms using categorical data. We investigated whether using continuous variables assigned different weights would improve risk stratification. We developed and validated a multivariable Cox model for relapse-free survival (RFS) using information from 21199 patients. We constructed risk groups by identifying cutoffs of the COG Prognostic Index (PICOG) that maximized discrimination of the predictive model. Patients with higher PICOG have higher predicted relapse risk. The PICOG reliably discriminates patients with low vs. high relapse risk. For those with moderate relapse risk using current COG risk classification, the PICOG identifies subgroups with varying 5-year RFS. Among current COG standard-risk average patients, PICOG identifies low and intermediate risk groups with 96% and 90% RFS, respectively. Similarly, amongst current COG high-risk patients, PICOG identifies four groups ranging from 96% to 66% RFS, providing additional discrimination for future treatment stratification. When coupled with traditional algorithms, the novel PICOG can more accurately risk stratify patients, identifying groups with better outcomes who may benefit from less intensive therapy, and those who have high relapse risk needing innovative approaches for cure.

Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group.

PURPOSE: To determine the incidence, risk factors, and morbidity for osteonecrosis (ON) in children with acute lymphoblastic leukemia (ALL) treated with intensive chemotherapy including multiple, prolonged courses of corticosteroid. PATIENTS AND METHODS: The occurrence of symptomatic ON was investigated retrospectively in 1, 409 children ages 1 to 20 years old receiving therapy for high-risk ALL on Children's Cancer Group (CCG) protocol CCG-1882. RESULTS: ON was diagnosed in 111 patients (9.3% +/- 0.9%, 3-year life-table incidence). The incidence was higher for older children (> or = 10 years: 14.2% +/- 1.3% v < 10 years: 0.9% +/- 0.4%; P: <.0001), especially females 10 to 15 years old and males 16 to 20 years old (19.2% +/- 2.3% and 20.7% +/- 4.7%, respectively). In patients 10 to 20 years old, the incidence of ON was higher for females versus males (17.4% +/- 2.1% v 11.7% +/- 1.6%, respectively; P: =.03) and for patients randomized to receive two 21-day dexamethasone courses versus one course (23.2% +/- 4.8% v 16.4% +/- 4.3%, respectively; P: =.27). Among ethnic groups, whites had the highest incidence and blacks the lowest, with other groups intermediate (16.7% +/- 1.4% v 3.3% +/- 2.3% v 6.7% +/- 2.2%, respectively; P: =.003). There was no difference in event-free survival in patients with or without ON. ON was diagnosed within 3 years of starting ALL therapy in all but one patient, involved weight-bearing joint(s) in 94% of patients, and was multifocal in 74% of patients. Symptoms of pain and/or immobility were chronic in 84% of patients, with 24% having undergone an orthopedic procedure and an additional 15% considered candidates for surgery in the future. CONCLUSION: Children ages 10 to 20 years who receive intensive ALL therapy, including multiple courses of corticosteroid, are at significant risk for developing ON.

Aeromonas abscess in an immunocompromised child.

An 11-year-old immunocompromised child developed cellulitis and abscess due to Aeromonas hydrophila at the site of bone marrow aspiration after swimming in a freshwater lake. The patient required treatment with intravenous antibiotics and surgical debridement to eradicate the infection. Both common and unusual organisms may complicate infections at the sites of percutaneous procedures.

Risk of cross-patient infection with clinical use of a needleless injector device.

BACKGROUND: Needleless injection devices use multiple-dose vials for the administration of local anesthetics to patients. There is a theoretic risk of iatrogenic infection associated with use of these devices. METHODS: This study used in vitro models to investigate the potential for transferring microbial pathogens among patients by using the Syrijet (Keystone Industries, Inc, Cherry Hill, NJ). Staphylococcus aureus and coagulase-negative staphylococci were used to determine whether patient skin flora could contaminate the instrument internal canal by postejection reverse flow and whether the staphylococci could survive on the ejection surface, in the internal canal, or in the anesthetic vial. RESULTS: The ejection surface was contaminated by firing the device while it was in contact with a contaminated surface. Postejection reverse flow drew contaminants into the device, and increased with ejection volume. Reverse flow did not reach the multidose vial, and staphylococci did not grow in the commercial anesthetic solution typically administered with the device. Surface, but not internal, contamination could be removed by swabbing with disinfectant. CONCLUSION: Although autoclaving is the only way to ensure sterilization of this device, frequent cleaning of the ejection surface during clinical use minimizes the risk of cross-patient bacterial transfer.

Sensitive detection of rare circulating neuroblastoma cells by the reverse transcriptase-polymerase chain reaction.

The presence of circulating tumor cells in patients with localized or disseminated neuroblastoma may be a significant prognostic factor at diagnosis and may antedate the detection of relapse by other diagnostic studies. We report the development of a highly sensitive detection assay for circulating neuroblasts based on the reverse transcriptase-polymerase chain reaction (RT-PCR), using the neuroendocrine protein gene product 9.5 (PGP 9.5) as the tumor marker. Analysis of RT-PCR products by agarose gel electrophoresis demonstrated that neuroblastoma cell lines were uniformly positive, whereas peripheral blood mononuclear cells were negative. Alkaline Southern blotting with a PGP 9.5-specific probe revealed scant expression of PGP 9.5 in peripheral blood mononuclear cells, well below the limits of detection by electrophoresis alone. The system was able to detect a single neuroblastoma cell in 10(7) peripheral blood mononuclear cells. Eighteen patient samples were analyzed by PGP 9.5 RT-PCR and the results compared with immunocytology in 16. Ten of the 18 were negative by both studies. Eight of the 18 were positive by PGP 9.5 RT-PCR, 4 of which were also positive by immunocytology. PGP 9.5 RT-PCR was able to detect circulating neuroblasts in two patients with negative immunocytology, the first with progressive bone marrow disease and the second at high risk for relapse but no other evidence of disease. PGP 9.5 RT-PCR allows the detection of circulating neuroblastoma cells with a sensitivity greater than immunocytology. It will be useful in evaluating the clinical significance of circulating tumor cells with respect to prognosis and early detection of relapse, and in the screening of peripheral stem cell harvests prior to autologous infusion.