Marcia Leonard

Treatment Outcome and Prognostic Factors for Infants With Acute Lymphoblastic Leukemia Treated on Two Consecutive Trials of the Children's Cancer Group

PURPOSE Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Childrens Cancer Group (CCG) protocols. PATIENTS AND METHODS Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS Most patients (>95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG- 1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG- 1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/microL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION Outcome for infants on CCG-107 and CCG- 1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.

Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers: Guidelines for the Assessment and Management of Female Reproductive Complications

PURPOSE As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. METHODS The Childrens Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. RESULTS This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. CONCLUSION Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.

Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Recent advances in treatment have led to dramatically improved survival rates. Standard ALL treatment includes multiple administrations of the chemotherapeutic drug vincristine, which is a known neurotoxic agent. Although peripheral neuropathy is a well‐known toxicity among children receiving vincristine acutely, the long‐term effects on the peripheral nervous system in these children are not clear. The objective of this study was to determine the prevalence of neuropathy and its impact on motor function and quality of life (QOL) among children who survived ALL. Thirty‐seven survivors of childhood ALL aged 8–18 underwent evaluation for neuropathy through self‐reported symptoms, standardized examinations, and nerve conduction studies (NCS). Functional impact of neuropathy was assessed using the Bruininks‐Oseretsky test of Motor Proficiency (BOT‐2). QOL was assessed using the PedsQL. Nerve conduction study abnormalities were seen in 29.7% of children who were longer than 2 years off therapy for ALL. Most children with an abnormal examination or NCS did not have subjective symptoms. Although overall motor function was below population norms on the BOT‐2, presence of neuropathy did not significantly correlate with motor functional status or QOL.

Sexual functioning in young adult survivors of childhood cancer

Background: Studies of sexuality or sexual behavior in childhood cancer survivors tend to examine relationships or achievement of developmental milestones but not physiological response to cancer or treatment. The purpose of this study is to (1) identify prevalence and risk factors for sexual dysfunction in childhood cancer survivors, and (2) examine the extent to which sexual dysfunction may be associated with health‐related quality of life (HRQOL) and psychosocial outcomes.

Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: A report from the Children's Cancer Group

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Children's Oncology Group's 2013 blueprint for research: Nursing discipline

Integration of the nursing discipline within cooperative groups conducting pediatric oncology clinical trials provides unique opportunities to maximize nursings contribution to clinical care, and to pursue research questions that extend beyond cure of disease to address important gaps in knowledge surrounding the illness experience. Key areas of importance to the advancement of the nursing disciplines scientific knowledge are understanding the effective delivery of patient/family education, and reducing illness‐related distress, both of which are integral to facilitating parental/child coping with the diagnosis and treatment of childhood cancer, and to promoting resilience and well‐being of pediatric oncology patients and their families. Pediatr Blood Cancer 2013; 60: 1031–1036.

Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma

Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/amplified in pediatric HGG, but the significance of this finding has not been fully characterized. We hypothesize that alterations of PDGFRA will promote distinct prognostic and treatment implications in pediatric HGG. In order to characterize the impact of PDGFR pathway alterations, we integrated genomic data from pediatric HGG patients (n=290) from multiple pediatric datasets and sequencing platforms. Integration of multiple human datasets showed that PDGFRA mutation, but not amplification, was associated with older age in pediatric HGG (P= <0.0001). In multivariate analysis, PDGFRA mutation was correlated with worse prognosis (P = 0.026), while PDGFRA amplification was not (P = 0.11). By Kaplan-Meier analysis, non-brainstem HGG with PDGFRA amplification carried a worse prognosis than non-brainstem HGG without PDGFRA amplification (P = 0.021). There were no pediatric patients with PDGFRA-amplified HGG that survived longer than two years. Additionally, we performed paired molecular profiling (germline / tumor / primary cell culture) and targeting of an infant thalamic HGG with amplification and outlier increased expression of PDGFRA. Dasatinib inhibited proliferation most effectively. In summary, integration of the largest genomic dataset of pediatric HGG to date, allowed us to highlight that PDGFRA mutation is found in older pediatric patients and that PDGFRA amplification is prognostic in non-brainstem HGG. Future precision-medicine based clinical trials for pediatric patients with PDGFRA-altered HGG should consider the optimized delivery of dasatinib.

Prevalence and Predictors of Sperm Banking in Adolescents Newly Diagnosed With Cancer: Examination of Adolescent, Parent, and Provider Factors Influencing Fertility Preservation Outcomes

Purpose To estimate the prevalence of sperm banking among adolescent males newly diagnosed with cancer and to identify factors associated with banking outcomes. Patients and Methods A prospective, single-group, observational study design was used to test the contribution of sociodemographic, medical, psychological/health belief, communication, and developmental factors to fertility preservation outcomes. At-risk adolescent males (N = 146; age 13.00 to 21.99 years; Tanner stage ≥ 3), their parents, and medical providers from eight leading pediatric oncology centers across the United States and Canada completed self-report questionnaires within 1 week of treatment initiation. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs for specified banking outcomes (collection attempt v no attempt and successful completion of banking v no banking). Results Among adolescents (mean age, 16.49 years; standard deviation, 2.02 years), 53.4% (78 of 146) made a collection attempt, with 43.8% (64 of 146) successfully banking sperm (82.1% of attempters). The overall attempt model revealed adolescent consultation with a fertility specialist (OR, 29.96; 95% CI, 2.48 to 361.41; P = .007), parent recommendation to bank (OR, 12.30; 95% CI, 2.01 to 75.94; P = .007), and higher Tanner stage (OR, 5.42; 95% CI, 1.75 to 16.78; P = .003) were associated with an increased likelihood of a collection attempt. Adolescent history of masturbation (OR, 5.99; 95% CI, 1.25 to 28.50; P = .025), banking self-efficacy (OR, 1.23; 95% CI, 1.05 to 1.45; P = .012), and parent (OR, 4.62; 95% CI, 1.46 to 14.73; P = .010) or medical team (OR, 4.26; 95% CI, 1.45 to 12.43; P = .008) recommendation to bank were associated with increased likelihood of sperm banking completion. Conclusion Although findings suggest that banking is underutilized, modifiable adolescent, parent, and provider factors associated with banking outcomes were identified and should be targeted in future intervention efforts.

Late Effects in Adolescent Survivors of Childhood Cancer

Abstract The late effects examination must not be regarded as merely an academic exercise or routine by the nurse. Much study, documentation, and time is needed to learn more about potential effects of cancer treatment. Children diagnosed as having cancer are entitled to quality long-term follow-up. The nurses role is extremely important in helping adolescents with a history of cancer face potential life changes. Prompt intervention may prevent further exaggeration of newly developed problems. The medical team must provide families with a concrete approach to any abnormalities or concerns. In addition, the late effects examination should furnish answers to questions the adolescent or his family may have regarding any aspect of the teens past or present health. The adolescent who is noncompliant for scheduled clinic visits presents another challenge to the oncology nurse. Phone contact should be maintained with those teens and their parents. Although this level of communication is not optimal, pertinent data regarding growth and development, school or employment, and social status, along with current state of health and any recent progeny can be ascertained. Maintaining telephone contact may also convey the treatment centers commitment to quality long-term care and prompt the adolescent or his family to return to the clinic. Lastly, the documentation of adverse late effects of cancer therapy should be looked upon by those performing late effects examinations as a strong incentive to continue the search for less toxic, but equally effective, treatment for childhood cancer.

Nurse-Led Programs to Facilitate Enrollment to Children’s Oncology Group Cancer Control Trials

The progress made over the past 50 years in disease-directed clinical trials has significantly increased cure rates for children and adolescents with cancer. The Children’s Oncology Group (COG) is now conducting more studies that emphasize improving quality of life for young people with cancer. These types of clinical trials are classified as cancer control (CCL) studies by the National Cancer Institute and require different resources and approaches to facilitate adequate accrual and implementation at COG institutions. Several COG institutions that had previously experienced problems with low accruals to CCL trials have successfully implemented local nursing leadership for these types of studies. Successful models of nurses as institutional leaders and “champions” of CCL trials are described.