Cameron K. Tebbi

Compliance of pediatric and adolescent cancer patients

Compliance with self‐administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age, 6.85 years) and 40 parents were extensively interviewed at 2 weeks, 20 weeks, and 50 weeks post‐diagnosis. The results of self‐reported compliance were corroborated by serum bioassay of the prescribed medications. A significant correlation between the age of patient and compliance with chemotherapeutic agents and nonchemotherapeutic medications was found (P < 0.05 and P < 0.02, respectively), with adolescent patients being compliant less often. Over the course of therapy, compliance among patients decreased, but not significantly. A significant negative correlation was found between compliance and the number of children in the family. Compilers and noncompliers did differ significantly in how well they understood instructions concerning how to take their medication (P = 0.04). No significant correlations between compliance and stage of the disease, number or type of drugs used, complexity of the regimen, degree of satisfaction with information given to the patient, understanding of disease, treatment, or belief in medication efficacy were found. The main reasons given for noncompliance were forgetfulness, busy schedules, and nonavailability of medication. More compilers than noncompliers were in agreement with their parents regarding who was responsible for the administration of the medication. Compliance is a complex and multifaceted issue which interrelates with a large number of medical and social factors. Cancer 58:1179‐1184, 1986.

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

To date, there is a lack of long‐term safety and efficacy data for iron chelation therapy in transfusion‐dependent patients with sickle cell disease (SCD). To evaluate the long‐term safety and efficacy of deferasirox (a once‐daily oral iron chelator), patients with SCD completing a 1‐year, Phase II, randomized, deferoxamine (DFO)‐controlled study entered a 4‐year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5‐year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow‐up (9·2%) and adverse events (AEs) (7·6%). Investigator‐assessed drug‐related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild‐to‐moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P = 0·027; n = 67). Long‐term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years.

Response-Dependent and Reduced Treatment in Lower Risk Hodgkin Lymphoma in Children and Adolescents, Results of P9426: A Report from the Children’s Oncology Group

Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes.

Religiosity and Locus of Control of Adolescent Cancer Patients

In an effort to assess religious beliefs and locus of control in adolescent oncology patients, the Faulkner-DeJong Religiosity and Nowicki-Strickland Locus of Control Scales were administered to 28 adolescent cancer patients treated at Roswell Park Memorial Institute. The adolescent cancer patients endorsed religiosity items at a level comparable to that of college students. Over-all, the majority of adolescent patients practiced their religion and indicated that this provided support by offering security in the face of death and by helping them understand and accept their experience. There were no significant relationships among any of the religiosity subscales or degree of use of religion as a secondary source of control and locus of control scores for adolescent cancer patients. Religiosity subscale scores and locus of control scores did not differ significantly as a function of sex, age, religion, or time since diagnosis. In contrast to established norms, locus of control scores were not significantly different for older and younger patients. Among younger adolescent cancer patients, the illness experience may have accelerated the development of internality associated with older adolescents.

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: A Pediatric Oncology Group (POG) study

The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD).

Self-reported depression in adolescent cancer patients.

The prevalence of depression was studied, using the Beck Depression Inventory (BDI) and Schedule for Affective Disorders and Schizophrenia (SADS), in a sample of 30 adolescent cancer patients. BDI scores revealed that 26 patients (87%) were not depressed, 4 (13%) were moderately depressed and no one had severe depression. Similarly, SADS data indicated no history of depression in 75% of the sample, and histories of minor and major depression in 14 and 10% of the sample, respectively. Females scored significantly higher (p > .05) than males on BDI physical, but not psychological, items. The average response to BDI physical items was significantly greater (p > .05) than to psychological items, suggesting that somatic symptoms are more salient than psychological symptoms of depression among adolescent cancer patients. Overall, however, as compared with norms, the rate of major depression among adolescent cancer patients is not greater than that for the population at large. These data do not exclude the possibility of masked symptoms, which only under stringent conditions will become obvious.

Acute megakaryoblastic leukemia associated with mosaic Down's syndrome

There have been several reports of the association between Downs Syndrome and acute megakaryoblastic (M7) leukemia (AMKL). The diagnosis of this rare form of leukemia has been better delineated by the use of the platelet peroxidase reaction and the antifactor VIII antibody immunoperoxidase test. In the past, the prognosis of patients with a combination of Downs Syndrome and AMKL has been extremely poor, with a median survival of 6.9 months for 11 reported cases in the literature. The present report reviews the previously reported cases and describes a unique patient with mosaic Downs syndrome and AMKL with favorable response to therapy.

Multimodality therapy for medulloblastoma.

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan‐Meier technique.

Toxicity of high dose Ara‐C in children and adolescents

The toxicity of high dose cytosine arabinoside (Ara‐C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitts lymphoma. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life‐threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara‐C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara‐C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness.

Rosai‐Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the familys place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically. Pediatr Blood Cancer 2006; 47:629–632.