Management considerations of Hodgkin lymphoma for patients with Fontan physiology.

While treatment protocols for Hodgkin lymphoma (HL) are well established, there is no literature available to guide therapy or estimate prognosis for patients with Fontan physiology who develop HL. The physiology of a Fontan procedure can result in the inability to tolerate chemotherapy toxicities, supportive care, and infection. We present a series of three patients with Fontan physiology who were treated for HL and discuss their clinical course and treatment.

Daily text message assessments of 6-mercaptopurine adherence and its proximal contexts in adolescents and young adults with leukemia: A pilot study.

BACKGROUND: This pilot study explored the feasibility and acceptability of implementing text-based assessments of oral chemotherapy adherence in adolescents and young adults (AYA) with leukemia. METHODS: AYA prescribed maintenance 6-mercaptopurine (6MP) received daily text message surveys and utilized an electronic pill bottle for 28 days. Text surveys assessed 6MP adherence and contextual associates (eg, mood). Feasibility was defined by recruitment/retention rates, survey completion rates, cost, and technical issues. After the 28-day period, AYA completed an acceptability survey. Secondary analyses compared text survey and electronic pill bottle adherence rates, and explored the daily associations between contextual factors and 6MP nonadherence. RESULTS: Eighteen AYA enrolled (M age = 18, range 15-22) and completed study procedures (100% recruitment and retention rates). Adherence survey completion rates were high (M = 88.9%), the technology cost was $204.00, and there were few technical issues. AYA reported high satisfaction with the surveys and perceived them as a helpful medication reminder. While not significantly correlated, survey and electronic pill bottle adherence data converged on the majority of days (>90%). Exploratory analyses showed that AYA were more likely to miss a dose of 6MP on weekends (OR = 2.33, P = .048) and on days when their adherence motivation (OR = 0.28, P = .047) and negative affect (OR = 3.92, P = .02) worsened from their own typical functioning. CONCLUSIONS: For AYA with leukemia, daily text-based surveys are a feasible and acceptable method for delivering medication adherence assessments, and may operate as a short-term intervention. To develop personalized mobile health interventions, findings also highlighted the need to study time-varying predictors of 6MP nonadherence.

Feasibility and acceptability of a pilot tailored text messaging intervention for adolescents and young adults completing cancer treatment.

PURPOSE: Despite cure, adolescents and young adults (AYA) who complete cancer treatment remain at risk for numerous physical and psychological late effects. However, engagement in recommended follow-up care, knowledge of cancer treatment history and risks, and adoption of health promoting behaviors are often suboptimal. The pilot randomized controlled trial assessed the feasibility and acceptability of a text messaging intervention (THRIVE; Texting Health Resources to Inform, motiVate, and Engage) designed to promote well-being, and health knowledge and behaviors. METHODS: Sixty-one AYA who recently completed cancer therapy enrolled and were randomized to receive THRIVE (n = 31) or an AYA survivor handbook (n = 30). Participants from both groups completed baseline measures and follow-up surveys 16 weeks later. AYA randomized to THRIVE received one to two health-related text messages per day over 16 weeks. RESULTS: THRIVE demonstrated a high level of acceptability and feasibility. Exploratory analyses highlighted promising improvements in knowledge, fruit/vegetable intake, and perceptions of health vulnerability. CONCLUSIONS: Text messaging is an acceptable and feasible intervention approach for improving well-being and health of AYA survivors. Future research is needed to test the impact of text messaging in a larger trial, including whether or not such an intervention can improve clinical outcomes, such as survivors' engagement in follow-up care.

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. RESEARCH DESIGN: We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. RESULTS: An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%-92%] and a positive predictive value of 93% (95% CI, 89%-96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%-1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%-1.60%) when ICD-9 codes alone were used. CONCLUSIONS: This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children's hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia.

BACKGROUND: Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one-tenth of ALL-associated mortality and half of ALL treatment-related mortality. We sought to ascertain patient- and hospital-level factors associated with induction mortality. PROCEDURE: We performed a retrospective cohort analysis of 8,516 children ages 0 to <19 years with newly diagnosed ALL admitted to freestanding US children's hospitals from 1999 to 2009 using the Pediatric Health Information System database. Induction mortality risk was modeled accounting for demographics, intensive care unit-level interventions, and socioeconomic status (SES) using Cox regression. The association of ALL induction mortality with hospital-level factors including volume, hospital-wide mortality and payer mix was analyzed with multiple linear regression. RESULTS: ALL induction mortality was 1.12%. Race and patient-level SES factors were not associated with induction mortality. Patients receiving both mechanical ventilation and vasoactive infusions experienced nearly 50% mortality (hazard ratio 122.30, 95% CI 66.56-224.80). Institutions in the highest induction mortality quartile contributed 27% of all patients but nearly half of all deaths (47 of 95). Hospital payer mix was associated with ALL induction mortality after adjustment for other hospital-level factors (P = 0.046). CONCLUSIONS: The overall risk of induction death is low but substantially increased in patients with cardio-respiratory and other organ failures. Induction mortality varies up to three-fold across hospitals and is correlated with hospital payer mix. Further work is needed to improve induction outcomes in hospitals with higher mortality. These data suggest an induction mortality rate of less than 1% may be an attainable national benchmark.

Protecting pediatric oncology patients from influenza.

Influenza is a common respiratory pathogen. Its severity can be unpredictable, but people with chronic illness are at increased risk of severe infection, complications, and death from influenza. This review examines evidence to support various strategies to protect pediatric oncology patients from influenza-related morbidity. Influenza vaccination should be considered standard. Additional evidence-supported measures include antiviral treatment, antiviral prophylaxis, cohorting of patients, and hospital infection control measures. Data from other high-risk populations support the vaccination of family members, double-dose or high-dose vaccination, and the use of barrier methods. These measures have the potential to optimize patient outcomes because there will be fewer treatment interruptions for acute illness. These strategies can also protect patients from prolonged hospitalizations and morbidity related to influenza.

Immunologic consequences of chemotherapy for acute myeloid leukemia.

There are few data characterizing the immunologic consequences of chemotherapy for acute myeloid leukemia (AML) and almost nothing is known about the effects of chemotherapy in a pediatric AML cohort. We identified T-cell subsets, B-cell subsets, and used Enzyme-linked immunosorbent spot analyses to define the function of T cells and B cells in 7 pediatric patients with AML on chemotherapy. The data show that the effects of chemotherapy disproportionately target the B cell and depletion of B cells is associated with impaired responses to the inactivated influenza vaccine. Diminished T-cell numbers were also observed although the magnitude of the effect was less than what was seen for B cells. Furthermore, measures of T-cell function were largely intact. We conclude that humoral immunity is significantly affected by chemotherapy for AML.

Successful whole lung lavage in a child with pulmonary alveolar proteinosis secondary to hematologic malignancy.

Pulmonary alveolar proteinosis (PAP) describes the accumulation of surfactant in the alveolar space. Secondary PAP has been reported in a variety of diseases, and in rare cases has been associated with hematologic malignancy. Treatment for PAP is based on the underlying disease process, and may include whole lung lavage, inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor, or statins. PAP secondary to hematologic malignancy has been reported to demonstrate poor response to whole lung lavage. We report a case of successful treatment of a pediatric patient with acute myeloid leukemia and secondary PAP using whole lung lavage.

Community acquired influenza requiring hospitalization: vaccine status is unrelated to morbidity in children with cancer.

BACKGROUND: Community acquired influenza can be severe and there are few data regarding hospitalization for children with cancer and influenza. Association between prior vaccination and infection severity has not been studied, although vaccination is standard practice. PROCEDURE: Patients with malignancy or prior stem cell transplant (SCT) were identified using a database of children with laboratory confirmed influenza (2000-2005). Other data collected included receipt of vaccine, absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). These were compared with intensive care unit (ICU) stay, respiratory complications and hospital days. RESULTS: There were 39 patients with laboratory-confirmed influenza with a median age of 6.9 years. Twenty-four (62%) were on cancer therapy at time of infection and 18 (46%) had received the influenza vaccination that season. Measures of immune status included ANC at time of infection (median 1,530 cells/microl; inter-quartile range, 315, 4347), presence of graft versus host disease 2 (5%) and steroid therapy 4 (10%) patients. All had a low ALC (median 448 cells/microl; IQR 189, 861). Respiratory complications occurred in 8 (20%), ICU admissions in 4 (10%) and death in 2 (5%) patients. Median hospital stay was 2 days. All ICU admissions occurred in unvaccinated patients (P = 0.1). Vaccine status, ANC (<1,000 cells/microl vs. >1,000) and ALC (<500 cells/microl vs. >500) were not associated with length of stay or respiratory complications. CONCLUSIONS: Influenza infection can be severe in children with cancer and complications occur despite vaccination. Prospective evaluation of vaccine response is worthy of future study.

The efficacy of influenza vaccination in a pediatric oncology population.

There is little known about the impact of the timing of influenza vaccine administration on seroconversion in patients on chemotherapy. Recommendations for other vaccines state that the vaccines should be readministered several months after the completion of chemotherapy outside of the stem cell transplant setting. This is not often possible with the influenza vaccine because of its seasonal nature. To examine whether certain times during chemotherapy are more favorable for seroconversion, we examined vaccine responses in a cohort of children on chemotherapy. Pediatric patients on chemotherapy were recruited over the 2006 to 2008 influenza vaccine seasons. Sixty-eight acute lymphoblastic leukemia (ALL), 3 acute myeloid leukemia, and 18 sarcoma patients were evaluated. Clinical and laboratory features were recorded. The hemagglutination inhibition (HAI) assay was used to define serotype-specific responses. Seroconversion rates varied according to the type of chemotherapy during the vaccination period. In some cases, there was a late rise in titer, suggesting that a wild-type infection had occurred, leading to an estimate of vulnerability of this population. In patients with ALL, responses to the vaccine were greater when it was given early in the course of treatment. We conclude that seroconversion rates are well below the rates cited for the general population. The 3 acute myeloid leukemia patients had a particularly poor response to the vaccine. In the case of ALL patients, it may be possible to adjust the timing of the vaccine to optimize the response.

Adherence to Multiple Treatment Recommendations in Adolescents and Young Adults with Cancer: A Mixed Methods, Multi-Informant Investigation.

Purpose: This mixed methods study sought to assess adolescent and young adult (AYA) adherence to three cancer treatment recommendations (medications, diet, physical activity), and determine the individual, family, and health system factors associated with suboptimal adherence. Methods: In Stage 1, 72 AYA-caregiver dyads completed a validated adherence interview and surveys about individual and family functioning. Matched providers (n = 34 who reported on 61 AYAs) completed global adherence ratings through survey. In Stage 2, a subset (n = 31) completed qualitative interviews. Results: Medication adherence was higher (M = 94.8%) than diet (M = 73.9%) and physical activity (M = 55.4%), although ≥50% demonstrated "Imperfect Adherence" for each subtask. Univariately, AYAs who missed a medication had more depressive symptoms, worse health-related quality of life (HRQOL), and more medication barriers; their families had more financial stress, worse family functioning, and lower self-efficacy. The odds of adhering to medications were lower with worse HRQOL (odds ratio [OR] = 1.08; 95% confidence interval [CI], 1.02-1.15) and family functioning (OR = 0.18; 95% CI, 0.04-0.91). The odds of adhering to physical activity and diet were lower with worse family functioning (OR = 0.09; 95% CI, 0.01-0.91) and more barriers (OR = 0.24, CI: 0.10-0.61), respectively. Qualitative themes further supported multilevel influences on AYA adherence. Conclusions: Adherence challenges were identified across medications, diet, and physical activity. Multilevel contextual factors were associated with suboptimal adherence, including poorer HRQOL and family functioning. Findings support the need to improve clinical adherence assessment and develop contextually tailored interventions.

Screening for depression and anxiety in adolescent cancer patients.

The goals of this study were to evaluate the feasibility of depression and anxiety screening in on-therapy adolescents with cancer, determine the prevalence of depression and anxiety in this sample, and assess the concordance between patient and oncologist report of patient symptoms. Forty-one adolescents (ages 12 to 18 y) undergoing cancer therapy in an outpatient oncology clinic completed the Beck Youth Inventory II (BYI II) Depression and Anxiety scales. Treating oncologists independently rated patient depression and anxiety. Ninety-eight percent of patients agreed to participate and average time to measure completion was <15 minutes. Mean T-scores for the BDI-Y (Depression module) and BAI-Y (Anxiety module) for most were not different than published norms. Three and 2 patients scored in the moderate-extremely elevated range of the BAI-Y and BDI-Y, respectively. There were no associations between scores and sex, age, diagnosis, time since diagnosis, or treatment intensity. A depression and anxiety-screening program is feasible in the outpatient pediatric oncology setting. Rates of adolescent self-reported anxiety and depression are low, although oncologists perceived more patient distress. This is an area for future investigation.

Gain-of-Function STAT1 Mutation With Familial Lymphadenopathy and Hodgkin Lymphoma.

In this report, we describe a novel T437N STAT1 mutation found in a mother and 3 of her 4 children which we demonstrate yields gain-of-function. All of the four patients with the T437N STAT1 mutation experienced lymphadenopathy. However, two of the children developed Nodular Lymphocyte Predominant Hodgkin Lymphoma (NHLPL) and have responded to chemotherapeutic regimens. The fourth sibling had neither the STAT1 variant nor lymphadenopathy or malignancy. To our knowledge this is the first description of a potential association between STAT1 GOF mutations and lymphoma development.

Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases.

Most primary bone lymphomas (PBLs) are diffuse large B-cell lymphomas (DLBCLs). Pediatric PBL-DLBCL has a favorable prognosis but remains poorly characterized. Herein, 10 such cases are detailed. They involved 11- to 20-year-old males with bone lesions that were often painful. They were diagnosed often after months to years of symptoms, suggesting an indolent disease. All were successfully treated with chemotherapy with or without radiotherapy (0.5- to 24-year followup). Biopsy revealed that the lymphomas were paratrabecular or diffuse and were medium- to large-sized with round to irregular nuclei, dispersed chromatin, indistinct to small nucleoli, and abundant cytoplasm. Other features included varying levels of necrosis, cytoplasmic retraction, and myeloid hyperplasia. All cases marked as mature B cells, and most were CD10+ (7/10). Typical centroblastic morphologic features with nucleoli were rare, multilobated nuclei were uncommon, and CD10 negativity did not predict poor prognosis, unlike in the adult PBL-DLBCL. These findings suggest that pediatric and adult PBL-DLBCLs are distinct entities.

Depression and anxiety in children at the end of life.

A significant component of palliative care is the prompt diagnosis and management of distress, anxiety, and depression. This article reviews the symptoms and treatment of anxiety and depressive disorders in children at the end of life. Distinguishing between symptoms and disorders, the importance of open communication, consideration of the child's understanding of death, diagnostic challenges in chronically ill children, and suicidality are discussed. Because treatment options are available, it is imperative that symptoms are recognized and addressed. Understanding the issues involved in screening and diagnosis and the risks and benefits of available treatments can lead to an informed approach to the management of these disorders in the palliative care setting.

Primary non-Hodgkin's lymphoma of bone in children.

BACKGROUND: Primary non-Hodgkin's lymphoma of bone, often more simply referred to as primary lymphoma of bone, is a rare subset of non-Hodgkin's lymphoma in children. There are only a few small series of primary lymphoma of bone in children with long-term follow-up, and none have appeared in the orthopaedic literature. METHODS: A review of our institution's Pediatric Tumor Registry identified fifteen cases of primary lymphoma of bone among 306 cases of diagnosed non-Hodgkin's lymphoma between 1970 and 2003. Retrospective evaluation included collection of demographic, clinical, radiographic, treatment, and follow-up data. A univariate analysis was used to assess the prognostic significance of risk factors with respect to survival of patients from this series and in a summary analysis of data collected from similar series in the literature. RESULTS: The patients included ten male and five female patients with a mean age of 11.6 years. Most patients had a presenting complaint of pain and had swelling and/or tenderness on physical examination. Eight children had a solitary bone lesion, and seven had multiple bone lesions. Overall, the mean number of bones involved was 3.1 per patient. The femur and the pelvis were the most frequently involved bones. The ten surviving patients were followed for a mean of 13.6 years. Five patients died: three of disease progression, one of treatment-related complications, and one of an unrelated cause. The mean time from diagnosis to death was 2.1 years. Nine patients received chemotherapy only, whereas six patients received a combination of chemotherapy and radiation therapy. In the present study, an age of nine years or less was predictive of poor survival (p < 0.05). In the summary analysis of cases collected from the literature, advanced stage, young age, non-large-cell histology, and multiple-bone involvement were predictive of poor survival (p < 0.05). CONCLUSIONS: On the basis of the present series and a comprehensive review of similar series in the literature involving patients with primary lymphoma of bone, it appears that younger age, advanced-stage disease, multiple-bone involvement, and non-large-cell histology are associated with decreased survival as compared with older age, localized disease, single-bone involvement, and large-cell histology, respectively.

"To be a phenomenal doctor you have to be the whole package": physicians' interpersonal behaviors during difficult conversations in pediatrics.

BACKGROUND: Delivery of bad news is a challenging task for physicians and other health care professionals. Several studies have assessed parental perceptions of the delivery of bad news, but none have focused on the role of physicians' interpersonal behaviors in the communication process. OBJECTIVE: The study's objective was to assess parental perceptions of physicians' interpersonal behaviors and their role in communication of bad news. DESIGN: The design was a cross-sectional qualitative interview study of 13 parents of patients hospitalized or previously hospitalized in the pediatric intensive care unit or oncology/bone marrow transplant unit at an academic children's hospital. RESULTS: Eleven interpersonal behaviors were identified as important by parents. The majority of parents identified empathy in physicians as critical. Availability, treating the child as an individual, and respecting the parent's knowledge of the child were mentioned by almost half of parents. Themes also considered important but by a smaller number of parents were allowing room for hope, the importance of body language, thoroughness, going beyond the call of duty, accountability, willingness to accept being questioned, and attention to the suffering of the child. CONCLUSIONS: To increase parental satisfaction and enhance the parent-physician therapeutic partnership, we recommend that physicians consider attending to the 11 interpersonal behaviors described in this manuscript, and that educational programs pay particular attention to these behaviors when training health care providers in the communication of bad news.

A prospective study of chemotherapy immunologic effects and predictors of humoral influenza vaccine responses in a pediatric oncology cohort.

BACKGROUND: Pediatric oncology patients represent a cohort of individuals uniquely at risk of complications from influenza, yet less likely to respond to the vaccine. It is not yet clear how to best protect this vulnerable population. METHODS: We performed a prospective analysis of 177 pediatric oncology patients to define the predictors of influenza vaccine responses. Each variable was examined over three time points and a repeated measure analysis was performed. RESULTS: Patients with ALL vaccinated during induction phase had superior influenza vaccine responses than those subjects vaccinated during post-induction or maintenance phases (P=0·0237). Higher aggregate HAI titer responses were associated with a higher baseline B-cell count (P=0·0240), and higher CD4 and CD8 influenza-specific T-cell responses, suggesting prior antigen exposure is a significant contributor. The solid tumor cohort had equivalent responses during all time frames of chemotherapy. DISCUSSION: The optimal protection from influenza of pediatric patients on chemotherapy should include vaccination, but it is clear that not all patients produce high titers of antibodies after vaccination. This study identified biomarkers that could be used to individualize vaccine approaches. Immunologic predictors might have a role in targeting resources, as B-cell counts predicted of vaccine responses among the patients with ALL.