Alessandra Sala

Protocol-based treatment for children with cancer in low income countries in Latin America: A report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)—Part II

Pediatric cancer programs in low‐income countries (LIC) can improve outcomes. However, treatment must be tailored to the patients living conditions and the availability of supportive care. In some cases, a more intense regimen will decrease survival since the increase in death from toxicity may exceed any decrease in relapse. Attempts to practice evidence‐based pediatric oncology are thwarted by the lack of evidence derived from local experience in LIC to determine optimal therapy. This report summarizes treatment regimens used by pediatric oncologists from 15 countries of the Caribbean, Central and South America who participate in the Monza International School of Pediatric Hematology/Oncology (MISPHO). Patients with hepatoblastoma, Wilms tumor, and histiocytosis treated on unmodified published protocols had outcomes comparable to those in high‐income countries (HIC). Those with rhabdomyosarcoma, osteosarcoma, Hodgkin lymphoma, and acute myeloid leukemia treated with unmodified regimens had event‐free survival estimates 10%–20% lower than those reported in HIC due to higher rates of toxic death, abandonment of therapy, and relapse. Treatment of retinoblastoma is complicated by advanced stages and extraocular disease at diagnosis; improved outcomes depend on education of pediatricians and the public to recognize early signs of this disease. Use of unmodified protocols for Burkitt lymphoma and acute lymphoblastic leukemia have been associated with unacceptable toxicity in LIC, so MISPHO centers have modified published regimens by giving lower doses of methotrexate and reducing use of anthracyclines. Despite the use of all‐trans‐retinoic acid during induction for acute promyelocytic leukemia, the incidence of fatal hemorrhage remains unacceptably high. Pediatr Blood Cancer

Nutritional status at diagnosis is related to clinical outcomes in children and adolescents with cancer: A perspective from Central America

BACKGROUND The prevalence of malnutrition in children may exceed 50% in countries with limited resources. The aims of this study were to assess nutritional status at diagnosis in children and adolescents with cancer, and to correlate it with clinical outcomes in the Spanish speaking countries of Central America that formed the AHOPCA (Asociacion de Hemato-Oncologia Pediatrica de Centro America) consortium. METHODS Patients aged 1-18 years, diagnosed with cancer between 1st October 2004 and 30th September 2007, were eligible for study. Weight (kg) and height or length (m), mid upper arm circumference--MUAC and triceps skin fold thickness--TSFT were measured and their Z-scores or percentiles were calculated. Three categories of nutritional status were defined according to these parameters. RESULTS A total of 2954 new patients were enrolled; 1787 had all anthropometric measurements performed and 1513 also had measurements of serum albumin. By arm anthropometry 322/1787 patients (18%) had moderate nutritional depletion and 813/1787 patients (45%) were severely depleted. Adding serum albumin, the proportion classified as severely depleted rose to 59%. Malnourished children more often abandoned therapy and their event free survival was inferior to that of other children. CONCLUSIONS Arm anthropometry in children with cancer is a sensitive measure of nutritional status. Since malnutrition at diagnosis was related to important clinical outcomes, an opportunity exists to devise simple, cost-effective nutritional interventions in such children that may enhance their prospects for survival.

Prevalence and predictors of abandonment of therapy among children with cancer in El Salvador

Abandonment of therapy is one of the most common causes of treatment failure among children with cancer in low‐income countries. Our objectives were to describe the prevalence and predictors of abandonment among such children with cancer in El Salvador. We analyzed data on patients younger than 16 years, diagnosed with any malignancy between January 2001 and December 2003 at the Benjamin Bloom National Childrens Hospital, San Salvador. Among 612 patients, 353 were male (58%); the median age at diagnosis was 5.1 years; 59% of patients were diagnosed with leukemia/lymphoma, 28% with solid tumors and 13% with brain tumors. The prevalence of abandonment was 13%. Median time to abandonment was 2.0 (range 0–36) months. In univariate analyses, paternal illiteracy [odds ratio (OR) 3.8, 95% confidence interval (CI) 2.0–7.2; p = 0.001]; maternal illiteracy (OR = 5.1, 95% CI 2.5–10; p < 0.0001); increasing number of household members (OR = 1.2, 95% CI 1.1–1.3; p = 0.004); and low monthly household income (OR per

Osteopenia and cancer in children and adolescents : The fragility of success

100 = 0.59, 95% CI 0.45–0.75; p < 0.0001) all significantly increased the risk of abandonment, whereas travel time to hospital did not. In multiple regression analyses, low monthly income and increased number of people in the household were independently predictive of abandonment. In conclusion, in El Salvador, despite the provision of free treatment, socioeconomic variables significantly predict increased risk of abandonment of therapy. Understanding the pathways through which socioeconomic status affects abandonment may allow the design of effective interventions.

Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala

The attainment of a satisfactory peak bone mass, which is accomplished largely by the end of adolescence, is the best protection against excessive bone mineral loss in late adulthood. Factors that influence this process include age, race, sex, body size, pubertal status, diet, physical activity, and other lifestyle elements. Cancer and its treatment in children and teenagers adversely impact bone mineralization. In particular, chemotherapy (especially glucocorticosteroids and methotrexate) and cranial irradiation (apparently by reducing growth hormone secretion and by causing hypogonadotropic hypogonadism) interfere with normal bone turnover. Resorption often exceeds formation, resulting in net bone mineral loss and providing a rational basis for the use of antiresorptive drugs. Such osteopenia may be symptomatic, with pain and abnormal gait, and increases the risk of fractures several fold. The disorder is compounded by reduced physical activity, so programs to reduce this deficit are of measurable benefit. All of those engaged in the care of children and adolescents with cancer have an opportunity to improve the bone health of these young people and to limit their risk of developing osteoporosis and fragility fractures in adult life. Cancer 2007;.

Bisphosphonate therapy for reduced bone mineral density during treatment of acute lymphoblastic leukemia in childhood and adolescence: a report of preliminary experience.

Most children with cancer live in developing countries where the prevalence of malnutrition may reach 50% and influence the course of the disease. This study examined the prevalence and severity of malnutrition at diagnosis, as well as after 3 and 6 months of chemotherapy, in children with acute lymphoblastic leukemia (ALL) in Guatemala.

Accounting for body size deviations when reporting bone mineral density variables in children

Background Osteopenia is a common consequence of the treatment of acute lymphoblastic leukemia (ALL) in children and adolescents, due predominantly to glucocorticosteroid therapy. The pathogenesis relates to an imbalance of resorption over formation of bone. Methods Alendronate (Fosamax), an inhibitor of osteoclastic bone resorption, was administered for at least 6 months to 15 children with ALL during maintenance chemotherapy, after the diagnosis of osteopenia/osteoporosis by dual energy x-ray absorptiometry. The height velocity was also measured during the administration of alendronate and again 2 years later. Results Areal bone mineral density Z scores of the lumbar spine had a median value of −1.32 before administration of alendronate and a median gain of +0.64, with 14/15 children showing improvement. There was no adverse effect of alendronate on height velocity, and the drug was well tolerated with no short-term toxicity. Conclusions This preliminary experience suggests a potential value in the use of alendronate for the treatment of osteopenia/osteoporosis in children with ALL and points to the need for a randomized controlled trial of this intervention.

Osteonecrosis in children and adolescents with cancer

SummaryIn a child, bone mineral density (BMD) may differ from an age-expected normal value, not only because of the presence of disease, but also because of deviations of height or weight from population averages. Appropriate adjustment for body size deviations simplifies interpretation of BMD measurements.IntroductionFor children, a bone mineral density (BMD) measurement is normally expressed as a Z score. Interpretation is complicated when weight or height distinctly differ from age-matched children. We develop a procedure to allow for the influence of body size deviations upon measured BMD.MethodsWe examined the relation between body size deviation and spine, hip and whole body BMD deviation in 179 normal children (91 girls). Expressions were developed that allowed derivation of an expected BMD based on age, gender and body size deviation. The difference between measured and expected BMD was expressed as a HAW score (Height-, Age-, Weight-adjusted score).ResultsIn a second independent sample of 26 normal children (14 girls), measured spine, total femur and whole body BMD all fell within the same single normal range after accounting for age, gender and body size deviations. When traditional Z scores and HAW scores were compared in 154 children, 17.5% showed differences of more than 1 unit and such differences were associated with height and weight deviations.ConclusionFor almost 1 in 5 children, body size deviations influence BMD to an extent that could alter clinical management.

Results of AIEOP LNH-97 protocol for the treatment of anaplastic large cell lymphoma of childhood†

Osteonecrosis is recognized increasingly as a complication of the treatment of cancer in young people, especially those with acute lymphoblastic leukemia and non‐Hodgkin lymphoma, reflecting a probable pathogenetic role of steroid therapy. Children ≥10 years of age and Whites are at particular risk, and genetic predispositions have been identified. The disorder affects weight‐bearing joints predominantly. It is commonly bilateral and multi‐articular. Treatment options include both surgical and non‐surgical interventions. Pediatr Blood Cancer 2008;50:483–485.

A survey of resources and activities in the MISPHO family of institutions in Latin America: A comparison of two eras†

Anaplastic large cell lymphoma (ALCL) represents approximately 15% of all pediatric non‐Hodgkin lymphomas (NHL). It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system (CNS). Despite varying treatment approaches the outcome of patients with ALCL has not significantly improved during the last two decades.