Susan Lindemulder

Fever and neutropenia in pediatric patients with cancer.

Aggressive treatment of childhood cancers including systemic antineoplastic and radiation therapy has secondary effects on a variety of normal cells including hematopoietic elements of the bone marrow, often causing neutropenia. Neutropenia increases the risk for serious infection and is associated with significant morbidity and mortality. The approach to the treatment of the febrile neutropenic pediatric patient has evolved considerably because high- and low-risk criteria have been defined and broad-spectrum antibiotics developed. This article reviews the concepts involved in the evaluation and management of febrile, neutropenic, pediatric cancer patients.

Successful Intermittent Prophylaxis With Trimethoprim/Sulfamethoxazole 2 Days per Week for Pneumocystis carinii (jiroveci) Pneumonia in Pediatric Oncology Patients

OBJECTIVE. This study was conducted to determine the efficacy of dosing trimethoprim/sulfamethoxazole on 2 consecutive days per week for the prevention of Pneumocystis carinii (jiroveci) pneumonia in a pediatric leukemia and lymphoma population and to determine whether trimethoprim/sulfamethoxazole contributes to neutropenia during maintenance therapy. METHODS. Charts were reviewed for all pediatric patients with leukemia and lymphoma diagnosed between January 1, 1993, and December 31, 2002. Data were collected through April 1, 2004. RESULTS. A total of 575 charts were reviewed; 529 patients were included in the analysis. A total of 482 (345 leukemia, 137 lymphoma) patients were evaluated on trimethoprim/sulfamethoxazole dosed 2 consecutive days per week for 268074 patient-days. No breakthrough cases were documented in compliant patients; 2 noncompliant patients developed P carinii pneumonia. A total of 238 patients who were on trimethoprim/sulfamethoxazole prophylaxis and 13 patients who were receiving an alternative medication prophylaxis were evaluated for neutropenia during maintenance therapy. The median number of maintenance days on trimethoprim/sulfamethoxazole was 605.5 days and on alternative drug was 617 days. The median number of neutropenic maintenance days on trimethoprim/sulfamethoxazole was 15.5 days and on the alternative drug was 16 days. The median proportion of neutropenic days per patient was 0.029 on trimethoprim/sulfamethoxazole and 0.022 on the alternative drug. CONCLUSIONS. Intermittent dosing of trimethoprim/sulfamethoxazole on 2 consecutive days per week is an effective alternative prophylactic regimen for P carinii pneumonia in pediatric patients with leukemia and lymphoma. This analysis does not support a difference in neutropenia during maintenance therapy between patients who are treated with trimethoprim/sulfamethoxazole versus an alternative drug.

Survivors of standard risk acute lymphoblastic leukemia do not have increased risk for overweight and obesity compared to non-cancer peers: A report from the Children's Oncology Group

We sought to determine whether survivors of standard risk ALL (SR‐ALL) treated without cranial radiation have increased risk for obesity by assessing changes in body mass index (BMI) during and after treatment; identifying contributing patient and treatment factors; comparing rates of overweight/obese to national health data.

Survivors of standard risk acute lymphoblastic leukemia do not have increased risk for overweight and obesity compared to non-cancer peers

We sought to determine whether survivors of standard risk ALL (SR‐ALL) treated without cranial radiation have increased risk for obesity by assessing changes in body mass index (BMI) during and after treatment; identifying contributing patient and treatment factors; comparing rates of overweight/obese to national health data.

Preventive antibiotics in pediatric patients with acute myeloid leukemia (AML)

Treatment of acute myeloid leukemia (AML) comes with a significant risk of life‐threatening infection during periods of prolonged severe neutropenia. We studied the impact of preventive intravenous (IV) antibiotic administration at onset of absolute neutropenia on the incidence and outcome of life‐threatening infections during treatment of childhood AML.

Reply to: Obesity is an important health problem in survivors of pediatric acute lymphoblastic leukemia

To the Editor:We appreciate the letter by Zhang.While there is a childhood obesity epidemic worldwide,[1] we found that survivors of standard risk acute lymphoblastic leukemia (SR-ALL) treated without cranial radiation (CRT)were not at increased long-term risk for obesity beyond that observed in a valid non-cancer comparison group.[2] Several differences between our manuscript and meta-analyses by Zhang likely contribute to our different conclusions.[3,4] We studied a homogeneous group of SR-ALL patients treated with regimens similar to contemporary Children’s Oncology Group therapies without CRT. The meta-analyses by Zhang include heterogeneous studies of patients with high-risk features, CRT, and treatment regimens dating back to 1967 from different countries, which may not be generalizable to current SR-ALL patients. Body mass index percentile (BMI%) and z-score are established measures of obesity, but require valid reference and comparison populations.[5] We analyzed BMI% as it is readily understood by clinicians, with established ranges for overweight (BMI% 85) and obese (BMI% 95). A comparison group of healthy children was obtained from National Health and Nutrition Examination Survey (NHANES) 2005–2006 data (the evaluation years for our patients) adjusted for age, race, and gender. BMI% for both ALL cases and the healthy comparison population were calculated based on the Centers for Disease Control and Prevention’s Growth Charts most recently revised in 2000 based on data from the 1960s through 1990s.[5] In Zhang’s meta-analyses, different reference populations were used to calculate z-scores for ALL cases. Z-scores were calculated from the reference population for many studies due to a lack of an appropriate comparison group. Instead, the investigators compared the z-scores of ALL patients to zero. Zero should not be the expected z-score in non-cancer peers from the same time period with the same distribution of age, race, and gender, as the general population is becoming increasingly obese. Furthermore, a BMI z-score of 0.83 compared to the reference population is below the BMI z-scores of 1.04 and 1.64 which correspond to BMI% of 85 (overweight) and 95 (obese), respectively. Based on World Health Organization criteria, overweight and obese correspond to z-scores of >2 and >3, respectively.[5] BMI increases with age in children and thus is not necessarily attributable to SR-ALL therapy. Additionally, if the actual population followed the BMI distribution of the CDC 2000 reference group then approximately 5% would have a BMI% greater than 95. However, NHANES 2003–2006 data show that 16.3% of children ages 2–19 years have a BMI% 95, so the distribution of BMI% is shifted toward higher percentiles in the actual non-cancer group compared to the reference.[6] In fact, though 39% of our cohort was overweight or obese, the relative risk was 1.028 [P1⁄4 0.738] compared to the 2005–2006 NHANES comparison population.[2] While we did not observe increased obesity in SR-ALL survivors treated without CRT, we agree that any observed obesity should be addressed, as in any child, given the associations with serious health conditions. Research is needed to determine if obesity worsens cardiovascular, musculoskeletal, and neurocognitive late effects of SR-ALL therapy.[7]