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Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.
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BACKGROUND: Vaccinations are a vital part of routine childhood and adolescent preventive care. We sought to identify current oncology provider practices, barriers, and attitudes towards vaccinating childhood and adolescent cancer patients and survivors. METHODS: We conducted a one-time online survey distributed from March-October 2018 to pediatric oncologists at nine institutions across the United States (N = 111, 68.8% participation rate). The survey included 32 items about vaccination practices, barriers to post-treatment vaccination, availability of vaccinations in oncology clinic, familiarity with vaccine guidelines, and attitudes toward vaccination responsibilities. Descriptive statistics were calculated in STATA 14.2. RESULTS: Participants were 54.0% female and 82.9% white, with 12.6% specializing in Bone Marrow Transplants. Influenza was the most commonly resumed vaccine after treatment (7030%). About 50%-60% were familiar with vaccine guidelines for immunocompromised patients. More than half (62.7%) recommended that patients restart most immunizations 6 months to 1 year after chemotherapy. Common barriers to providers recommending vaccinations included not having previous vaccine records for patients (56.8%) or lacking time to ascertain which vaccines are needed (32.4%). Of participants, 66.7% stated that vaccination should be managed by primary care providers, but with guidance from oncologists. CONCLUSIONS: Many pediatric oncologists report being unfamiliar with vaccine guidelines for immunocompromised patients and almost all report barriers in supporting patients regarding vaccines after cancer treatment. Our findings show that further research and interventions are needed to help bridge oncology care and primary care regarding immunizations after treatment.
Subject(s)
Influenza Vaccines , Neoplasms , Child , Adolescent , Humans , Female , United States , Male , Vaccination , Immunization , Neoplasms/drug therapy , Surveys and Questionnaires , Health Knowledge, Attitudes, PracticeABSTRACT
Background: There is a need for platelet products to have the best quality. Apheresis platelet concentrates (PCs) obtained from single-donors PCs (SD-PCs) are considered best but have issues such as feasibility and cost. Buffy-coat pooled PCs (BCP-PCs) are considered an alternative to SD-PCs. This study compares BCP-PCs and SD-PCs for in vitro quality parameters and their changes during storage. Materials and Methods: Fifteen units of BCP-PCs and 15 units of SD-PCs were prepared. In this study, a pool of five buffy coats was prepared. Fifteen units of BCP-PCs were analyzed on day 1 and day 5 of storage, while 15 SD-PCs were analyzed on day 1 while ten units on day 5. The parameters analyzed were volume, hematological parameters, pH, swirling, and sterility. Results: The mean platelets count of SD-PCs was found to be significantly higher as compared to BCP-PCs. White blood cells (WBCs) contamination was significantly lower in BCP-PCs as compared to SD-PCs. The mean pH and mean platelet volume of SD-PCs were significantly lower than BCP-PCs. During storage, the mean platelets count of BCP-PCs was decreased significantly while that of SD-PCs nonsignificantly. The mean WBCs count and pH decreased in both BCP-PCs and SD-PCs significantly. All units in both types of PCs were sterile. Conclusion: Platelet yield was significantly better in SD-PCs, while mean WBCs contamination was significantly lower in BCP-PCs. BCP-PCs may be preferred in place of SD-PCs in case of nonavailability of apheresis, difficulty in finding a willing donor, or when the cost is of consideration.
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Objective: To evaluate the coagulation status of children with decompensated chronic liver disease (DCLD) and infection and factors affecting it using thromboelastography (TEG). Methods: Coagulation status of children admitted with DCLD and infection was assessed by international normalized ratio (INR), platelet count, and TEG [reaction time (R), kinetic time (K), α-angle (AA), maximum amplitude (MA), coagulation index (CI), and lysis index (LY30)] at admission and at 7-14 days after treatment. CI < -3 represents hypocoagulable state. Clinical profile including systemic inflammatory response syndrome (SIRS), infection severity, bleeding, treatment response, and outcome were noted. Results: Thirty children (21 boys, median (IQR) age 78 [15.7-180] months) were studied prospectively. At admission, 29 (96.7%) had prolonged INR, 24 (80%) had thrombocytopenia, and 17 (56.6%) were hypocoagulable by TEG. Nine of 30 (30%) had normal TEG but deranged INR and platelets. Nineteen (63.3%) cases had SIRS, 11 (36.6%) had severe sepsis, and 8 (26.6%) had bleeding. Hypocoagulable state was common in severe sepsis than sepsis/infection (81.1% versus 42.1%; P = 0.05) and persistent (n = 4) versus recovered SIRS (n = 15, 100% versus 33%; P = 0.03). Bleeders had prolonged R-time (7.8 versus 5.4 min; P = 0.03), smaller MA (30.2 versus 47 mm; P = 0.05), and α-angle (40.4 versus 62.9; P = 0.03) but similar INR and platelets than nonbleeders. Six patients (20%) had poor in-hospital outcomes; R-time ≥8.5 min predicted mortality with high sensitivity (83%) and specificity (100%). Conclusions: Fifth-seven percent of children with DCLD and infection were hypocoagulable by TEG. Severe sepsis and persistent SIRS worsened the coagulation status. TEG identifies bleeders better than INR and platelet count. R-time ≥8.5 min predicts a poor hospital outcome.
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Importance: Down syndrome (DS), caused by an extra copy of material from chromosome 21, is one of the most common genetic conditions. The increased risk of acute leukemia in DS (DS-AL) has been recognized for decades, consisting of an approximately 150-fold higher risk of acute myeloid leukemia (AML) before age 4 years, and a 10- to 20-fold higher risk of acute lymphoblastic leukemia (ALL), compared with children without DS. Observations: A recent National Institutes of Health-sponsored conference, ImpacT21, reviewed research and clinical trials in children, adolescents, and young adults (AYAs) with DS-AL and are presented herein, including presentation and treatment, clinical trial design, and ethical considerations for this unique population. Between 10% to 30% of infants with DS are diagnosed with transient abnormal myelopoiesis (TAM), which spontaneously regresses. After a latency period of up to 4 years, 20% to 30% develop myeloid leukemia associated with DS (ML-DS). Recent studies have characterized somatic mutations associated with progression from TAM to ML-DS, but predicting which patients will progress to ML-DS remains elusive. Clinical trials for DS-AL have aimed to reduce treatment-related mortality (TRM) and improve survival. Children with ML-DS have better outcomes compared with non-DS AML, but outcomes remain dismal in relapse. In contrast, patients with DS-ALL have inferior outcomes compared with those without DS, due to both higher TRM and relapse. Management of relapsed leukemia poses unique challenges owing to disease biology and increased vulnerability to toxic effects. Late effects in survivors of DS-AL are an important area in need of further study because they may demonstrate unique patterns in the setting of chronic medical conditions associated with DS. Conclusions and Relevance: Optimal management of DS-AL requires specific molecular testing, meticulous supportive care, and tailored therapy to reduce TRM while optimizing survival. There is no standard approach to treatment of relapsed disease. Future work should include identification of biomarkers predictive of toxic effects; enhanced clinical and scientific collaborations; promotion of access to novel agents through innovative clinical trial design; and dedicated studies of late effects of treatment.
Subject(s)
Down Syndrome , Leukemia, Myeloid, Acute , Leukemoid Reaction , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Infant , Child , Adolescent , Young Adult , Humans , Child, Preschool , Down Syndrome/complications , Down Syndrome/genetics , Leukemoid Reaction/complications , Leukemoid Reaction/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapyABSTRACT
Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between year 2000 to 2021. Median time from diagnosis to relapse was 6.8 (range, 1.1-45.5) months. Three-year event-free survival (EFS) and overall survival (OS) were 20.9 ± 5.3% and 22.1 ± 5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (hazard ratio [HR], 0.28), duration of first complete remission (CR1) (HR, 0.31 for > 12 months) and attainment of remission after relapse (HR, 4.03). Patients who achieved complete remission (CR) before HSCT, had an improved OS and EFS of 56.0 ± 11.8% and 50.5 ± 11.9%, respectively compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0 ± 9.5%). Treatment failure after HSCT was predominantly because of disease recurrence (52%) followed by treatment-related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.
Subject(s)
Down Syndrome , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Child , Retrospective Studies , Down Syndrome/complications , Down Syndrome/therapy , RecurrenceABSTRACT
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.
Subject(s)
Bacterial Infections , Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Leukemia, Myeloid, Acute , Neutropenia , Sepsis , Humans , Child , Sepsis/epidemiology , Central Venous Catheters/adverse effects , Leukemia, Myeloid, Acute/complications , Neutropenia/complications , Neutropenia/epidemiology , Doxorubicin , Catheterization, Central Venous/adverse effects , Risk Factors , Catheter-Related Infections/etiologyABSTRACT
Background: Knowledge of underlying pathophysiology of coagulopathy is evolving and the pattern of coagulation parameters in coronavirus disease 2019 (COVID-19)-associated diseases is still not very clear. Aims: In the present study, we aimed to find out the pattern and distribution of conventional coagulation parameters and thromboelastographic (TEG) parameters in COVID-19-associated coagulopathy (CAC) in survivors and nonsurvivors at 28 days. Setting and Design: The present prospective observational study was conducted at a tertiary care COVID-19 intensive care unit (ICU) facility from March 21, 2020, to July 15, 2021. Materials and Methods: Admission clinical and laboratory data (conventional coagulation, inflammatory and TEG parameters, and disease severity parameters) of 64 COVID-19 patients admitted to the ICU were collected. Patients were divided into two groups, i.e., survivors and nonsurvivors. Statistical Analysis: Data were compared between two groups, i.e., survivors versus no survivors on 28 days using Student's t-test/Mann-Whitney U-test or Chi-square test/Fisher's exact test. Results: Admission mean plasma fibrinogen levels (474.82 ± 167.41 mg.dL-1) and D-dimer were elevated (1.78 [0.66, 3.62] mg.mL-1) in the COVID-19 ICU patients. Overall, COVID-19 patients had mean lower normal platelet count (150 ± 50 × 103 cells.mm-3), with marginally elevated prothrombin time (16.25 ± 3.76 s) and activated partial thromboplastin time (38.22 ± 16.72 s). A 65.6% (42/64) TEG profile analysis showed a normal coagulation profile, and the rest 21.9% (14/64) and 12.5% (8/64) had hypercoagulable and hypocoagulable states, respectively. Plasma D-dimer level was markedly elevated in nonsurvivors compared to survivors (P < 0.05), while no other conventional coagulation parameters and TEG profile demonstrated statistically significant between the two groups. Conclusion: Markedly elevated plasma D-dimer level was observed in nonsurvivors of COVID-19 ICU patients. A large portion of COVID-19 ICU patients had a normal TEG profile. Conventional coagulation parameters and TEG profile were similar between survivors and nonsurvivors.
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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.
Subject(s)
Leukemia, Myeloid, Acute/therapy , Neutropenia/etiology , Outcome Assessment, Health Care/statistics & numerical data , Quality of Life/psychology , Adolescent , Child , Child, Preschool , Cohort Studies , Drug Therapy/methods , Drug Therapy/psychology , Drug Therapy/statistics & numerical data , Family/psychology , Female , Humans , Interviews as Topic/methods , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/epidemiology , Male , Neutropenia/epidemiology , Outcome Assessment, Health Care/methods , Pediatrics/methods , Pediatrics/statistics & numerical data , Qualitative ResearchABSTRACT
Acute lymphoblastic leukemia (ALL) is a heterogenous hematological malignancy representing 25% of all cancers in children less than 15 years of age. Significant improvements in survival and cure rates have been made over the past four decades in pediatric ALL treatment. Asparaginases, derived from Escherichia coli and Erwinia chrysanthemi, have become a critical component of ALL therapy since the 1960s. Asparaginases cause depletion of serum asparagine, leading to deprivation of this critical amino acid for protein synthesis, and hence limit survival of lymphoblasts. Pegaspargase, a conjugate of monomethoxypolyethylene glycol (mPEG) and L-asparaginase, has become an integral component of pediatric upfront and relapsed ALL protocols due to its longer half-life and improved immunogenicity profile compared to native asparaginase preparations. Over the past two decades great strides have been made in outcomes for pediatric ALL due to risk stratification, incorporation of multiagent chemotherapy protocols, and central nervous system prophylaxis with pegaspargase having played an important role in this success. However, adolescents and young adults (AYA) with ALL when treated on contemporaneous trials using adult ALL regimens, continue to have poor outcomes. There is increasing realization of adapting pediatric trial regimens for treating AYAs, especially those incorporating higher intensity of chemotherapeutic agents with pegaspargase being one such agent. Dose or treatment-limiting toxicity is observed in 25-30% of patients, most notable being hypersensitivity reactions. Other toxicities include asparaginase-associated pancreatitis, thrombosis, liver dysfunction, osteonecrosis, and dyslipidemia. Discontinuation or subtherapeutic levels of asparaginase are associated with inferior disease-free survival leading to higher risk of relapse, and in cases of relapse, a higher risk for remission failure. This article provides an overview of available evidence for use of pegaspargase in pediatric acute lymphoblastic leukemia.
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Context: Hemostatic abnormalities are more common in patients with brain tumors than systemic malignant diseases. Conventional coagulation tests (CCT) are poor assays for dynamic assessment of clot strength in whole blood. Thromboelastography (TEG) gives us detailed information on the dynamics of clot development, stabilization, and dissolution reflecting in vivo hemostasis. TEG can assess both thrombosis and fibrinolysis. Aims: This study aimed to investigate the temporal trends in hemostatic profile occurring during surgery for primary brain tumors, using a combination of TEG and CCT, and to assess perioperative blood component support. Subjects and Methods: A prospective, observational study was done on 40 patients with primary brain tumors larger than 4 cm in maximum diameter on computed tomography or magnetic resonance imaging. The tests (TEG and CCT [PT, INR, activated partial thromboplastin time, and platelet count]) were performed preoperatively (on the day of surgery), intraoperatively (2 h into surgery), and postoperatively (the day after surgery). Statistical Analysis: SPSS Version 21.0 statistical analysis software was used. Results: We found a universal trend toward hypercoagulability (persistent decrease in R-time, K-time and increase in MA, α-angle, Coagulation Index) in all the TEG parameters measured intraoperatively and postoperatively even though the values were within normal limits. Results of CCT had poor correlation with TEG parameters. The mean intraoperative blood loss was 737.7 ± 185.6 mL, for which PRBC was transfused in 17 patients, FFP in 13, but no platelet transfusion was done intraoperatively. Conclusions: We found a trend toward hypercoagulability in our study in intraoperative and postoperative period using TEG which was not evident on CCT. TEG was a useful diagnostic tool to identify coagulation abnormalities and to guide perioperative blood transfusion.
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Background: Panobinostat demonstrates activity against pediatric cancers in vitro. A phase I trial in children with refractory hematologic malignancies was conducted. Study design: The trial evaluated two schedules of oral panobinostat using 3 + 3 dose escalations in 28-day cycles. For children with leukemia, panobinostat was given once daily three days a week each week at 24, 30 and 34 mg/m2/day. For children with lymphoma, panobinostat was given once daily three days a week every other week at 16, 20 and 24 mg/m2/day. Cerebrospinal fluid (CSF) from Day 29 of the first cycle, when available, was evaluated for PK. The study was registered on clinicaltrials.gov (NCT01321346) Results: Twenty-two subjects enrolled with leukemia. Five enrolled at dose level 1, 6 at dose level 2, and 11 at dose level 3. There was one dose limiting toxicity (DLT) in the leukemia arm at dose level 3 (Grade 4 hypertriglyceridemia), but no maximum tolerated dose (MTD) was identified. No subjects required removal from protocol therapy for QTc prolongation. PK studies were available in 11 subjects with similar exposure in children as in adults. Four Day 29 CSF specimens were found to have panobinostat levels below the lower limit of quantification. Five subjects with lymphoma were enrolled and received study drug, and 4 were evaluable for DLT. A DLT was reported (Grade 3 enteritis) on the lymphoma arm. Conclusions: Panobinostat was tolerated in heavily pretreated pediatric subjects. Gastrointestinal effects were observed on this study. There were no cardiac findings. There were no responses.
Subject(s)
Hematologic Neoplasms/drug therapy , Leukemia/drug therapy , Lymphoma/drug therapy , Panobinostat/administration & dosage , Administration, Oral , Adult , Child , Female , Hematologic Neoplasms/blood , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/chemically induced , Leukemia/blood , Lymphoma/blood , Male , Panobinostat/adverse effects , RecurrenceABSTRACT
Assessing quality of life (QOL) outcome helps to show the effect of antiretroviral therapy (ART) on the subjective perception of its benefits among patients with HIV. A cross-sectional assessment of QOL, using the World Health Organization WHOQOL-HIV, on 204 HIV patients taking ART in western India showed patients with HIV on ART as having the best QOL score in the spiritual domain and the worst in the environment domain. Patients who are single, highly educated, of higher occupational status, with no HIV-positive children, not undergoing frequent hospital admissions, with access to a counsellor for support, who are not stigmatised or discriminated against due to HIV status, who do not have guilt or suicidal ideas, and who are theist, tend to have a better QOL, irrespective of their clinical condition or ART regimen. Patients' personal perceptions and feelings, societal support or stigma, and sociodemographic status have a more significant influence on QOL than clinical variables.
Subject(s)
HIV Infections/psychology , Quality of Life/psychology , Anti-HIV Agents/therapeutic use , Cross-Sectional Studies , HIV Infections/drug therapy , Humans , India/epidemiology , Social Stigma , Social Support , Socioeconomic Factors , Surveys and QuestionnairesSubject(s)
Antibodies, Bispecific/therapeutic use , Antineoplastic Agents/therapeutic use , Philadelphia Chromosome , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Child , Child, Preschool , Female , Humans , Male , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , RecurrenceABSTRACT
Neonatal aortic thrombosis is a rare occurrence but can be life-threatening. Most aortic thrombosis in neonates is related to umbilical artery catheters. A case of a neonate with a spontaneous aortic thrombosis is described here along with a comprehensive review of the literature for cases of neonatal aortic thrombosis not related to any intravascular device or procedure. The aetiologies of these spontaneous thromboses and the relevance of hypercoagulable disorders are discussed. The cases were analysed for odds of death by treatment method adjusted for era. The reference treatment method was thrombolysis and anticoagulation. No other treatment modality had significantly lower odds than the reference. Surgery alone had higher odds for death than the reference, but this may be confounded by severity of case. The management recommendations for clinicians encountering neonates with spontaneous neonatal aortic thrombosis are discussed.
Subject(s)
Aorta, Thoracic/pathology , Aortic Diseases/diagnosis , Fibrinolytic Agents/therapeutic use , Thrombosis/diagnosis , Aortic Diseases/drug therapy , Diagnosis, Differential , Humans , Infant, Newborn , Magnetic Resonance Imaging , Male , Thrombolytic Therapy , Thrombosis/drug therapyABSTRACT
PURPOSE: Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution. PATIENTS AND METHODS: We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range, 1-21) were treated in this trial. RESULTS: The most common grade 3-4 toxicities included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%). Three subjects experienced dose-limiting toxicities, which included cholestasis, steatosis, and hyperbilirubinemia (n = 1); seizure, somnolence, and delirium (n = 1); and pneumonitis, hypoxia, and hyperbilirubinemia (n = 1). Infectious complications were common with 17 of 23 (74%) subjects experiencing grade ≥3 infections including invasive fungal infections in 35% (8/23). Nine subjects (39%) achieved a complete response (CR + CR without platelet recovery + CR without neutrophil recovery) and five had stable disease (22%). Nine (39%) subjects were not evaluable for response, primarily due to treatment-related toxicities. Correlative pharmacodynamics demonstrated potent in vivo modulation of epigenetic marks, and modulation of biologic pathways associated with functional antileukemic effects. CONCLUSIONS: Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities. This study is registered at http://www.clinicaltrials.gov as NCT01483690.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Asparaginase/administration & dosage , Bortezomib/administration & dosage , Child , Child, Preschool , Decitabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Infant , Male , Mitoxantrone/administration & dosage , Neoplasm Recurrence, Local/pathology , Pilot Projects , Polyethylene Glycols/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Prognosis , Salvage Therapy/methods , Survival Rate , Vincristine/administration & dosage , Vorinostat/administration & dosage , Young AdultABSTRACT
CONCLUSIONS: Unlike weak D and partial D, DEL represents a weakened form of D that cannot be detected by conventional serology and requires use of an adsorption-elution method for its detection; therefore, DEL+ samples might be mistyped as D-. The study was undertaken to determine the prevalence of the DEL phenotype among D- blood donors from northern India. A total of 1003 D- blood donors were tested for weak D and DEL by the indirect antiglobulin test and an adsorption-elution method, respectively. Of the total 21,135 blood donors typed for D, 20,132 (95.3%) were D+ and 1003 (4.7%) gave a negative reaction for D. Of the total 1003 D- samples, 8 (0.8%) were weak D and only 2 (0.2%) were DEL+ by adsorption-elution testing. For samples that typed as D-, the majority of individuals (91.1%) were cde/cde (rr) followed by dCe/dce (r´r) in 4.8 percent, and dCe/dCe (r´r´) in 2.2 percent. Both DEL+ samples were also C+. We conclude that the prevalence of the DEL phenotype as detected by serology in D- north Indian blood donors is 0.2 percent, although it is as high as 2.8 percent in D-C+ individuals. There is an association of DEL with C, which can be used as a cost-effective marker for screening large numbers of D- blood donors for DEL.
Subject(s)
Blood Donors , Phenotype , Rh-Hr Blood-Group System/genetics , Alleles , Humans , IndiaABSTRACT
Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.
Subject(s)
Asparaginase , Bacterial Proteins , Desensitization, Immunologic , Drug Hypersensitivity/prevention & control , Polyethylene Glycols , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Asparaginase/administration & dosage , Asparaginase/adverse effects , Asparaginase/immunology , Bacterial Proteins/administration & dosage , Bacterial Proteins/adverse effects , Bacterial Proteins/immunology , Child , Child, Preschool , Dickeya chrysanthemi/enzymology , Drug Hypersensitivity/immunology , Escherichia coli/enzymology , Female , Humans , Male , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathologyABSTRACT
Social media as an effective source of information and support among parents and other caregivers of children with cancer has not been explored. The purpose of this cross-sectional study was to describe caregivers' reasons for using social media, social media sites used, and predictors of social media usage. This study sample included 215 caregivers (96% parents) of children with cancer receiving cancer-related care at a tertiary children's hospital in the Intermountain West. Most of caregivers (74%) reported using social media in relation to their child's cancer and reported using social media to provide and receive support and information about their child's diagnosis or treatment. Our findings suggest that social media could be a delivery platform for future interventions seeking to meet the informational and emotional needs of caregivers of children with cancer. An awareness of how parents and caregivers of children receiving cancer-related treatment use social media can help nurses understand their ongoing informational and emotional needs. Nurses can also support parents and caregivers in selecting reputable sources of support that are accessible via social media.
Subject(s)
Caregivers/psychology , Neoplasms/psychology , Parents/psychology , Social Media , Social Support , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , United States , Young AdultABSTRACT
The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.