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Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-related morbidity, but is not fully representative of the spectrum of events experienced by pediatric and aging adult survivors of childhood cancer. Also, CTCAE characterization does not routinely integrate detailed patient-reported and medical outcomes data available from clinically assessed cohorts. To address these deficiencies, we standardized the severity grading of long-term and late-onset health events applicable to childhood cancer survivors across their lifespan by modifying the existing CTCAEv4.03 criteria and aligning grading rubrics from other sources for chronic conditions not included or optimally addressed in the CTCAEv4.03. This manuscript describes the methods of late toxicity assessment used in the St. Jude Lifetime Cohort (SJLIFE) Study, a clinically assessed cohort in which data from multiple diagnostic modalities and patient-reported outcomes are ascertained.

O ver the last 3 decades, therapeutic progress has resulted in a growing population of survivors of childhood cancer. In 2006, there were Ͼ 11 million cancer survivors in the United States, three times the number of survivors in 1971. 1 The 5-year survival rate for children diagnosed with cancer is approaching 85%, 2 and an estimated one in 570 individuals in the United States between the ages of 20 and 34 is a survivor of childhood cancer. 3 Unfortunately, increased survival rates are not without consequences. There is substantial evidence Background: The purpose of this article is to summarize the literature that documents the longterm impact of cancer treatment modalities on pulmonary function among survivors of cancer and to identify potential areas for further research. Methods: Systematic reviews of clinical trials, observational studies, case series, and review articles were conducted. Articles were limited to the studies that discussed pulmonary toxicity or late effects among pediatric cancer survivors and to follow-up investigations that were conducted a minimum of 2 years after completion of cancer-related treatment or 1 year after hematopoietic stem cell transplant. Results: Sixty publications (51 clinical studies/reports and nine reviews) published from January 1970 to June 2010 in PubMed met the inclusion criteria. Data showed an association between radiotherapy, alkylating agents, bleomycin, hematopoietic stem cell transplant, and thoracic surgery and pulmonary toxicity, as well as possible interactions among these modalities. Conclusions: Pulmonary toxicity is a common long-term complication of exposure to certain anticancer therapies in childhood and can vary from subclinical to life threatening. Pulmonary function and associated loss of optimal exercise capacity may have adverse effects on long-term quality of life in survivors. Lung function diminishes as a function of normal aging, and the effects of early lung injury from cancer therapy may compound these changes. The information presented in this review is designed to provide a stimulus to promote both observational and interventional research that expands our knowledge and aids in the design of interventions to prevent or ameliorate pulmonary late effects among survivors of childhood cancer. CHEST 2011; 140(4):881-901Abbreviations: ALL 5 acute lymphoblastic leukemia; BCNU 5 carmustine; CCNU 5 lomustine; D lco 5 diffusing capacity of the lung for carbon monoxide; GVHD 5 graft-vs-host disease; gy 5 gray; HL 5 Hodgkin's lymphoma; HSCT 5 hematopoietic stem cell transplant; NHL 5 non-Hodgkin's lymphoma; PFT 5 pulmonary function testing; TLC 5 total lung capacity

Relatively little is known about the antigenic structure of Pneumocystis carinii and the immunopathogenesis of pneumonitis caused by P. carinii. To begin to define the antigenic character of the surface of this organism, we have produced murine monoclonal antibodies that react with the surface of P. carinii (obtained from rats), as detected by immunofluorescence and immunoelectron microscopy. Immunoblot analysis revealed that the six antibodies described in this report bound an antigen with an apparent molecular mass of 90,000-95,000 daltons. Although all six monoclonal antibodies bound P. carinii obtained from rats, only one (5E12) was also able to bind P. carinii obtained from rabbits, ferrets, and a human; this result demonstrated that isolates of P. carinii obtained from different species are not antigenically identical.

We prospectively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period (median follow-up, 376 days). Externalized catheters (91 Hickman [H], 113 Broviac [B]) and implantable ports (n = 82) were compared for complications, including infection and thrombosis. The most frequent major complication of all catheters was infection, although the rates of infection varied with the duration of catheter use and were generally lower than reported by others. Overall, when catheter failures (removal) for infection, obstruction, or dislodgement were considered, ports had a significantly longer failure-free duration of use (P = .0024) than did externalized catheters. Likewise, ports had a significantly longer infection-free (P less than .01) duration of use than H and B catheters. However, differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome. In analysis of pairs matched for diagnosis, therapy, and age, ports had lower infection rates than did B catheters after 100 days (P = .053). This difference became significant at 400 days of catheter use (P = .029). Although there was a trend toward lower rates of infections for ports v H catheters, this difference was not significant. In view of our results in matched pairs, selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports. The superiority of ports for long-term use (greater than 100 days) needs to be confirmed in a large randomized clinical trial.

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BACKGROUND:The number of long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasing; however, few studies have addressed their long-term pulmonary function. METHODS: The authors examined 660 baseline and follow-up pulmonary function tests in 89 long-term survivors of pediatric hematologic malignancies and allo-HSCT. RESULTS: At least 1 abnormal lung parameter was seen in 40.4% of baseline tests and developed in 64% of post-allo-HSCT tests (median follow-up: 8.9 years). Abnormal baseline values in ratio of forced expiratory volume in 1 second and forced vital capacity (FEV 1 /FVC), FEV 1 , residual volume (RV), functional residual capacity (FRC), and FVC were associated with abnormal post-allo-HSCT values. The following pulmonary function values declined significantly with time: FEV 1 /FVC, forced mid-expiratory flow (FEF 25%-75% ), total lung capacity (TLC), diffusion capacity corrected for hemoglobin (DLCO corr ), RV, FRC, and RV/TLC. Older age at the time of allo-HSCT was associated with lower FEV 1 /FVC, FEF 25%-75% , and DLCO corr and higher RV/TLC. Patients who experienced respiratory events within 1 year post-allo-HSCT had lower FEV 1 and FVC values and higher RV/TLC from their baseline pulmonary function tests. Female patients had reduced FVC, TLC, and RV values but higher FEV 1 /FVC. Pulmonary dysfunction was also associated with high-risk hematological malignancies and peripheral blood HSC product. CONCLUSIONS: Abnormal pulmonary functions in allo-HSCT survivors are prevalent, which underscore the need for risk-adapted continual monitoring and improved preventive and management strategies.

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