Citations

Abstract Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

AbstractBackgroundCommunity-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.MethodsWe evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes.ResultsOf the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01–1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05–1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36–2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15–4.62]) was associated with bacterial coinfection.ConclusionsCommunity-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Abstract Background Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients. Methods We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity. Results Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78–2.15; P = .32). Conclusions Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19.

Abstract Background It is unclear how acute coronavirus disease 2019 (COVID-19)-directed therapies are used in children with life-threatening COVID-19 in US hospitals. We described characteristics of children hospitalized in the intensive care unit or step-down unit (ICU/SDU) who received COVID-19-directed therapies and the specific therapies administered. Methods Between March 15, 2020 and December 27, 2020, children <18 years of age in the ICU/SDU with acute COVID-19 at 48 pediatric hospitals in the United States were identified. Demographics, laboratory values, and clinical course were compared in children who did and did not receive COVID-19-directed therapies. Trends in COVID-19-directed therapies over time were evaluated. Results Of 424 children in the ICU/SDU, 235 (55%) received COVID-19-directed therapies. Children who received COVID-19-directed therapies were older than those who did not receive COVID-19-directed therapies (13.3 [5.6-16.2] vs 9.8 [0.65-15.9] years), more had underlying medical conditions (188 [80%] vs 104 [55%]; difference = 25% [95% CI: 16% to 34%]), more received respiratory support (206 [88%] vs 71 [38%]; difference = 50% [95% CI: 34% to 56%]), and more died (8 [3.4%] vs 0). Of the 235 children receiving COVID-19-directed therapies, 172 (73%) received systemic steroids and 150 (64%) received remdesivir, with rising remdesivir use over the study period (14% in March/April to 57% November/December). Conclusion Despite the lack of pediatric data evaluating treatments for COVID-19 in critically ill children, more than half of children requiring intensive or high acuity care received COVID-19-directed therapies.

Abstract CXCR4, the chemokine receptor for stromal derived factor-1 (SDF-1) plays an important role in the homing and migration of hematopoietic stem cells. Selective inhibition of the binding of the CXCR4 receptor by the molecule AMD3100 leads to the mobilization of hematopoietic progenitors, including CD34+ cells into the circulation, even in the steady state. Preliminary studies have indicated that AMD3100 given 10–11 hours before each apheresis along with standard doses of G-CSF mobilizes more CD34+ cells per kilogram than does G-CSF alone. A Phase II study of this combination in patients with NHL and myeloma is underway. G-CSF at 10μg/kg/day for a duration of up to 9 days is administered with AMD3100 at 240 μg/kg/day starting on the evening of day 4 of G-CSF therapy, (10–11 hours prior to first and subsequent daily aphereses) until 5 x 106 CD34/kg are collected, or for a maximum of 5 days of a standard 3 blood volume apheresis. Both agents are administered subcutaneously. To date 20 patients (myeloma-6, NHL-14) have been enrolled and analyzed. Of these 20, 14 are considered to have been ‘heavily pre-treated’ using standard definitions (≥ 10 cycles of chemotherapy, platinum based salvage chemotherapy and/or radiation therapy to bone marrow sites). Blood CD34 assays (cells/μl) were performed before and after each AMD 3100 dose and on each apheresis product. After the first dose of AMD3100 there was a 2.6 fold increase in CD34/μl in blood (23 → 60 CD34+ cells/μl). The median number of apheresis performed was 2 (range 1–5); the median total CD34 collected for all 20 patients was 5.7 x 106/kg (range 2.32–14.58 x 106/kg). All patients had collections of > 2.0 x106 CD34/kg, and in 12 of 20 the 5 x 106 CD34/kg cell dose goal was collected, including 8 of 14 in the heavily pre-treated group. In fact in 6, the 5 x 106 CD34/kg cell dose was collected in a single apheresis. The median CD34/kg cell dose collected for the 14 heavily pre-treated patients was 5.7 x 106/kg (2.32–6.48 x 106/kg). There were no serious AE’s related to the use of AMD3100. Transient GI toxicity (mostly diarrhea) occurred in 10 of 20 patients shortly after the injections of AMD3100, but only 3 required therapy. Engraftment data is available for the first 12 patients treated. Time to ANC >500/μl and platelets > 20,000/μl was 9 (range 8–10) and 12 (range 9–19) days respectively. This novel combination of AMD3100 and G-CSF appears to be effective in mobilizing large numbers of CD34+ cells, even in patients considered to be heavily pre-treated, and is an effective alternative to chemotherapy/cytokine mobilization. Compared to studies of G-CSF alone, this combination may reduce the number of apheresis procedures needed to collect an adequate graft for rapid hematopoietic engraftment. The study is ongoing with accrual to date of 40 patients.

Abstract Background: Conventional AlloTx for MM is associated with TRM exceeding 20%. Non-myeloablative AlloTx (NST) utilizes the known graft-vs-myeloma (GVM) effect in an attempt to eradicate minimal residual disease. Preliminary studies of NST in MM demonstrated significant CR and low 100 day post-NST TRM (Badros et al Blood97:2574, 2001). However, even though response rates were high, the vast majority of pts with significant MM disease at the time of transplant, relapsed within the first year. To provide maximal tumor cytoreduction to allow for a subsequent GVM effect, the ECOG designed a Phase II trial of AHSCT for maximal tumor cytoreduction followed by a matched sibling NST to allow for a GVM effect. Methods: The study was designed as a two-stage process based upon early transplant mortality in the first 100 days. Eligibility included pts treated as part of induction therapy or salvage therapy. Chemotherapy responsive disease was not required. Only matched sibling donors were allowed. Pts must have had adequate PS and physiologic organ function. After stem cell mobilization, pts received melphalan 200 mg/m2 with AHSCT. Pts underwent NST 100–182 d post-AHSCT following fludarabine 30 mg/m2 daily × 5 and cyclophosphamide 1 g/m2 for 2 days. GVHD prophylaxis included cyclosporine and corticosteroids. For pts with acute GVHD, Zenapax 1 mg/kg for 5 doses q 3 d was recommended. GM-CSF was incorporated post-AHSCT and NST. The primary endpoints were day 100 TRM, early graft failure, extent of acute GVHD, toxicities, DFS and OS. The study was suspended for 6 mo after the first 19 pts to evaluate early TRM-no early TRM was observed and the study was re-opened. Results: From 5/3/01 to 1/14/05, 32 pts from 10 institutions were enrolled on the study. 23 patients, median age 51 (range 32–64) completed both transplants (28% drop-out rate): 7 (30%) CR (2 in CCR), 11 (48%) PR and 2 (9%) NR and 3 (13%) NE as the best overall response. Of the 32 pts who completed AHSCT, there were 12 grade 4 toxicities pre-NST; 11/23 pts had grade 4 toxicities post-NST. Acute grade III/IV GVHD was observed in 4 (17%); chronic GVHD was observed in 9 pts (39%): 5 limited; 4 extensive resulting in 3 CR (33%), 1 CCR, and 3 PR (33%). 1 pt (4%) had graft-failure. Two pts (8.7%; 95% CI 1.6%, 24.9%) had TRM prior to day + 100 post-NST. With a median follow up of 3.5 years from registration, the median PFS was 4.4 years and the 2-year survival rate was 78% (95% CI: 61% ∼ 95%) for the 23 pts who completed both transplants. Conclusions: AHSCT followed by NST is feasible in a Cooperative Group setting with a low early TRM. The PFS and OS were superior to historical reports for single and tandem AHSCT. AHSCT-NST tandem transplants resulted in a 78% overall response, including 30% CR (2/7 CCR) - similar to other reports for AHSCT-NST. 3/9 pts with chronic GVHD achieved CR demonstrating the GVM effect. However, a plateau in PFS or OS was not observed indicating that the GVM effect is not sufficient to produce long- term disease control and is unlikely curative using this treatment schema. Future studies should include novel therapies to induce better responses pre-transplant and consideration for post-NST maintenance to further eradicate MRD while allowing for GVM.