Child and family perceptions of satisfaction with neutropenia management in pediatric acute myeloid leukemia.

PURPOSE: Chemotherapy for pediatric acute myeloid leukemia (AML) is very intensive and many, but not all centers, require extended hospitalization until neutrophil recovery. Child and family preferences, beliefs, and experiences around hospitalization have not been systematically assessed. PATIENTS AND METHODS: We recruited children with AML and their parents from nine pediatric cancer centers across the United States for a qualitative interview about their experiences of neutropenia management. Interviews were analyzed using a conventional content analysis approach. RESULTS: Of 116 eligible individuals, 86 (74.1%) agreed to participate. Interviews were conducted with 32 children and 54 parents from 57 families. Of these 57 families, 39 were cared for as inpatients and 18 were managed as outpatients. A very high proportion of respondents in both groups reported satisfaction with the discharge management strategy recommended by the treating institution: 86% (57 individuals) of respondents who experienced inpatient management and 85% (17 individuals) of respondents who experienced outpatient management expressed satisfaction. Respondent perceptions associated with satisfaction related to safety (access to emergency interventions, infection risk, close monitoring) and psychosocial concerns (family separation, low morale, social support). Respondents believed it could not be assumed that all children would have the same experience due to varied life circumstances. CONCLUSION: Children with AML and their parents express a very high degree of satisfaction with the discharge strategy recommended by their treating institution. Respondents saw a nuanced tradeoff between patient safety and psychosocial concerns that was mediated by a child's life circumstances.

Risk of bacterial bloodstream infection does not vary by central-line type during neutropenic periods in pediatric acute myeloid leukemia.

BACKGROUND: Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy. OBJECTIVE: To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML. METHODS: We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics. RESULTS: The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar. CONCLUSIONS: In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Lymphocyte HLA-DR/CD-38 co-expression correlates with Hodgkin lymphoma cell cytotoxicity in vitro independent of PD-1/PD1-L pathway.

The interactions between Hodgkin and Reed Sternberg cells and tumor microenvironment, the changes that occur with therapy and, in particular, checkpoint inhibition are not fully understood. Understanding these is key to optimizing outcomes for patients with Hodgkin lymphoma (HL). We evaluated the immunophenotypic characteristics of cytotoxic, helper T and NK lymphocytes upon in vitro stimulation, cell-mediated cytotoxicity against HL cells, HDLM-2 and KM-H2, and the association with effector cell activation state, as well as changes in cytotoxicity following PD-1 or PDL-1 blockade. Higher HLA-DR/CD38 expression on effector cells was associated with increased cytotoxicity against HL cells. All effector cell types were cytotoxic of HL cells, though achieved maximum activation and cytotoxicity at variable timepoints. HLA-DR/CD38 co-expression correlated with cytotoxicity, but PD-1 expression did not. There was no significant change in cell-mediated cytotoxicity following PD-1/PDL-1 blockade. The mechanism of action of checkpoint inhibitors may not be limited to direct PD-1/PDL-1 blockade.

A Case Report of Intracardiac Hodgkin Lymphoma in an Adolescent Female.

Primary cardiac tumors are quite rare in children, and only a small portion are malignant. Presenting symptoms may be nonspecific, often mimicking those of congestive heart failure, pulmonary embolism, and syncope. Due to location and potential detrimental outcomes, diagnosis and management are of the utmost importance. Secondary and metastatic cardiac tumors are more frequent in comparison to primary tumors of the heart. Primary Hodgkin lymphoma of the heart is exceedingly rare with no standardized approach for treatment. Here we describe a case of an adolescent girl with primary cardiac Hodgkin lymphoma.

Medical Outcomes, Quality of Life, and Family Perceptions for Outpatient vs Inpatient Neutropenia Management After Chemotherapy for Pediatric Acute Myeloid Leukemia.

Importance: Pediatric acute myeloid leukemia (AML) requires multiple courses of intensive chemotherapy that result in neutropenia, with significant risk for infectious complications. Supportive care guidelines recommend hospitalization until neutrophil recovery. However, there are little data to support inpatient over outpatient management. Objective: To evaluate outpatient vs inpatient neutropenia management for pediatric AML. Design, Setting, and Participants: This cohort study used qualitative and quantitative methods to compare medical outcomes, patient health-related quality of life (HRQOL), and patient and family perceptions between outpatient and inpatient neutropenia management. The study included patients from 17 US pediatric hospitals with frontline chemotherapy start dates ranging from January 2011 to July 2019, although the specific date ranges differed for the individual analyses by design and relative timing. Data were analyzed from August 2019 to February 2020. Exposures: Discharge to outpatient vs inpatient neutropenia management. Main Outcomes and Measures: The primary outcomes of interest were course-specific bacteremia incidence, times to next course, and patient HRQOL. Course-specific mortality was a secondary medical outcome. Results: Primary quantitative analyses included 554 patients (272 [49.1%] girls and 282 [50.9%] boys; mean [SD] age, 8.2 [6.1] years). Bacteremia incidence was not significantly different during outpatient vs inpatient management (67 courses [23.8%] vs 265 courses [29.0%]; adjusted rate ratio, 0.73; 95% CI, 0.56 to 1.06; P = .08). Outpatient management was not associated with delays to the next course compared with inpatient management (mean [SD] 30.7 [12.2] days vs 32.8 [9.7] days; adjusted mean difference, -2.2; 95% CI, -4.1 to -0.2, P = .03). Mortality during intensification II was higher for patients who received outpatient management compared with those who received inpatient management (3 patients [5.4%] vs 1 patient [0.5%]; P = .03), but comparable with inpatient management at other courses (eg, 0 patients vs 5 patients [1.3%] during induction I; P = .59). Among 97 patients evaluated for HRQOL, outcomes did not differ between outpatient and inpatient management (mean [SD] Pediatric Quality of Life Inventory total score, 70.1 [18.9] vs 68.7 [19.4]; adjusted mean difference, -2.8; 95% CI, -11.2 to 5.6). A total of 86 respondents (20 [23.3%] in outpatient management, 66 [76.7%] in inpatient management) completed qualitative interviews. Independent of management strategy received, 74 respondents (86.0%) expressed satisfaction with their experience. Concerns for hospital-associated infections among caregivers (6 of 7 caregiver respondents [85.7%] who were dissatisfied with inpatient management) and family separation (2 of 2 patient respondents [100%] who were dissatisfied with inpatient management) drove dissatisfaction with inpatient management. Stress of caring for a neutropenic child at home (3 of 3 respondents [100%] who were dissatisfied with outpatient management) drove dissatisfaction with outpatient management. Conclusions and Relevance: This cohort study found that outpatient neutropenia management was not associated with higher bacteremia incidence, treatment delays, or worse HRQOL compared with inpatient neutropenia management among pediatric patients with AML. While outpatient management may be safe for many patients, course-specific mortality differences suggest that outpatient management in intensification II should be approached with caution. Patient and family experiences varied, suggesting that outpatient management may be preferred by some but may not be feasible for all families. Further studies to refine and standardize safe outpatient management practices are warranted.

Patterns and correlates of preserved humoral immunity to vaccines in children following allogeneic hematopoietic stem cell transplantation.

Data on preservation of vaccine immunity following allogeneic HSCT in children is limited. We investigated vaccine titers and sought correlations with patient characteristics in this study. Twenty-eight cases were retrospectively analyzed. Antibody concentrations against hepatitis A, hepatitis B, 3 poliovirus serotypes, tetanus, diphtheria, measles, mumps, rubella, varicella, and 13 pneumococcus serotypes were measured as part of planned monitoring following HSCT. Protective antibody levels were found for hepatitis A in 79% of the recipients, measles in 54%, all poliovirus serotypes in 50%, tetanus in 50%, rubella in 50%, varicella in 46%, hepatitis B in 46%, mumps in 43%, diphtheria in 29%, and ≥7/13 pneumococcus serotypes in 46%; lowest level observed for diphtheria and highest for hepatitis A prior to starting post-HSCT immunizations. In univariate analysis, patients with non-malignant diseases (P = .03) and without GvHD (P = .04) had more protective titers. A significant positive association was found among vaccine titers against the microorganisms or the serotypes of the same microorganism, which were administered together in the same product, including polio serotypes, diphtheria and tetanus, mumps, measles, and rubella. Higher degrees of sero-positivity are likely to be due to lack of prior chemotherapy in non-malignant disease cases and lesser immunosuppression in patients without GvHD. Monitoring long-term vaccine titers and administering vaccines accordingly could be evaluated for post-HSCT re-immunization practice.

Differing reflections of paediatric classical Hodgkin's lymphoma on local and distant immunological microenvironments: a flow cytometric study.

AIMS: To compare immunological microenvironments in local and distant lymphoid tissues in Hodgkin's lymphoma (HL) in children. METHODS: We have analysed diagnostic bone marrow (BM) samples in 22 and corresponding involved lymph node (LN) in eight and peripheral blood (PB) in eight cases of HL by flow cytometry and sought correlations with clinical features retrospectively. RESULTS: While there were significant differences in lymphocyte compositions of BM and LN tissues, the distribution of lymphocyte subsets mimicked each other in BM and PB. CD8-positive cytotoxic T cells predominate the bone marrow in contrast to CD4-positive helper T cells in LN tissue with corresponding CD4/CD8 ratios (0.85 and 5.3, respectively; p=0.002). Additionally, T-large granular lymphocytes population was much higher in BM in comparison to LN tissue (10.5% vs 4.5%; p=0.036). CONCLUSIONS: Local immunological microenvironment appears to be highly influenced by HL tumour cells and distant site lymphocyte composition reflects immune response to control the neoplastic process.

Role of Initiating Supportive Care Preceding Veno-occlusive Disease Diagnosis Following Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Severe veno-occlusive disease (VOD) following hematopoietic stem cell transplantation has a high mortality rate. The clinical course of VOD, role of preemptive and aggressive supportive care, and outcomes were investigated in a retrospective study from 2007 to 2014. Defibrotide was not available in all but one case with VOD at our center during the study. Forty-nine allogeneic transplants with intravenous busulfan-based or total body irradiation-based myeloablative conditioning were included. The median after hematopoietic stem cell transplantation day for suspicion of developing VOD (pre-VOD phase) was 6 due to weight gain, hepatomegaly, and/or mild increase in total bilirubin without fulfilling the modified Seattle criteria in 22 cases (45%). Despite fluid restriction, aggressive diuresis, and fresh frozen plasma infusions, 16 patients (33%) developed VOD by +10 days. Five cases (31%) had severe, 9 (56%) moderate, and 2 (13%) mild VOD. Eight cases (50%) required transfer to intensive care. One patient was given defibrotide, which was later discontinued due to concerns of adverse effects. Day +100 survival was 100% with complete resolution of VOD. Preemptive and aggressive supportive care could help achieve favorable outcomes in VOD and may have ameliorated the severity. This approach may be combined with other measures in the prevention/treatment of VOD.

Flow cytometry for assessment of the tumor microenvironment in pediatric Hodgkin lymphoma.

BACKGROUND: The role of flow cytometry in diagnosis and management of Hodgkin lymphoma (HL) remains limited. As knowledge emerges of the tumor microenvironment in this disease, various methods are being evaluated in its study. This study examines the microenvironment using flow cytometry to assess differences between subtypes and clinicopathologic correlates. PROCEDURE: A retrospective cross-sectional study was performed analyzing the tumor immunophenotype, by flow cytometry, for 31 children with classical HL. Correlation was made with patient information, including outcome. RESULTS: The makeup of the tumor microenvironment varies across subtype of HL, with T cells predominating in nodular sclerosis (NS), and similar proportions of B and T cells in mixed cellularity (MC). CD4 cells predominate in NS, whereas CD8 more so in MC subtype. The rate of continuous complete remission is significantly higher in the MC subgroup. Last, the proportion of HLA-DR/CD38 copositive lymphocytes was an independent prognostic factor for relapse/refractoriness. CONCLUSIONS: This study indicates that flow cytometry can be used to examine the tumor microenvironment in HL and that percentage of HLA-DR/CD38 copositive lymphocytes may be a biomarker for relapse and refractoriness in pediatric HL.

Identifying patient- and family-centered outcomes relevant to inpatient versus at-home management of neutropenia in children with acute myeloid leukemia.

Efficacy of therapeutic strategies relative to patient- and family-centered outcomes in pediatric oncology must be assessed. We sought to identify outcomes important to children with acute myeloid leukemia and their families related to inpatient versus at-home management of neutropenia. We conducted qualitative interviews with 32 children ≥8 years old and 54 parents. Analysis revealed the impact of neutropenia management strategy on siblings, parent anxiety, and child sleep quality as being outcomes of concern across respondents. These themes were used to inform the design of a questionnaire that is currently being used in a prospective, multiinstitutional comparative effectiveness trial.

Supportive care in pediatric oncology: oncologic emergencies and management of fever and neutropenia.

Advancements in the care of children with cancer have, in part, been achieved through improvements in supportive care. Situations that require prompt care can occur at the time of presentation as well as during treatment. This article discusses the approach to children with fever and neutropenia, a complication encountered daily by care providers, as well as oncologic emergencies that can be seen at the time of a child's initial diagnosis: hyperleukocytosis, tumor lysis syndrome, superior vena cava syndrome, and spinal cord compression.

Myelofibrosis, hepatic extramedullary hematopoiesis and ascites associated with vitamin D deficiency in early infancy.

Primary myelofibrosis is rare in children. Many causes have been described for secondary myelofibrosis including vitamin D deficiency. Here, we describe a patient with myelofibrosis secondary to vitamin D deficiency, as diagnosed by laboratory evidence. The patient also developed resultant extramedullary hematopoiesis with secondary development of ascites as a result of myelofibrosis. These are findings rarely reported in association with vitamin D deficiency. Potential mechanisms are also discussed.

Controversies in the role of radiotherapy in the treatment of pediatric Hodgkin lymphoma.

Hodgkin lymphoma in children is a highly curable malignancy with current approaches utilizing combined modality therapy and a risk-adapted approach. The combination of anthracyclines, bleomycin, and radiotherapy, as well as other alkylating agents, are significant risk factors for secondary malignancies and cardiopulmonary toxicity. Therefore, current strategies aim to optimize cure rates while minimizing late effects. The role of radiotherapy has been examined in recent pediatric trials, with varying results. However, they provide evidence, as a whole, for the omission of radiotherapy for a subgroup of patients, without compromising outcomes.