Faculty Bibliography

Respiratory viral infections (RVIs) affect children year-round, with seasonal-specific patterns. Pediatric oncology patients are uniquely vulnerable to infection, but whether this predisposes them to different patterns of RVIs than healthy children is unknown. There is also limited data on the impact of RVIs on cancer patients. We conducted a retrospective study of children ages 1-21 with cancer presenting to the clinic and emergency department (ED) and a randomly selected subset of patients without cancer presenting to the ED who had positive nasopharyngeal viral polymerase chain reactions at our institution from 2014 to 2019. Sixty-seven cancer patients (206 RVI episodes) and 225 pediatric non-cancer patients (237 RVI episodes) were included. Human rhino/enterovirus (HRE) was the most common infection in both groups in the spring, summer, and fall. In the winter, the most common RVI was influenza in cancer patients verses respiratory syncytial virus in non-cancer patients. On age-adjusted analysis, the likelihood of detecting coronavirus in the winter, HRE in the spring and fall, and parainfluenza in the summer was significantly greater in cancer patients (OR = 2.60, 2.52, 5.73, 3.59 respectively). Among cancer RVI episodes, 50% received parenteral antibiotics, 22% were severely neutropenic, 22% had chemotherapy delays for a median of six days, 16% were hospitalized, and 6% received intravenous immunoglobulin. We conclude that there are differences in the seasonal patterns of RVIs between children with and without cancer. RVIs also cause significant morbidity in children with cancer.

Infections are responsible for most treatment-related morbidity and mortality in pediatric acute myeloid leukemia (AML). Children's Oncology Group (COG) recommends hospitalization following chemotherapy until early absolute neutrophil count (ANC) recovery. No standard guidelines exist for antibiotic prophylaxis and discharge practices vary. Our objective was to report our institution's experience with outpatient supportive care management following early discharge. A retrospective chart review of pediatric AML patients treated at our institution from 2010 to 2019 was conducted. Data was collected on length of hospitalization, antibiotics administered, infections, and neutropenia duration. Seventeen patients underwent 60 chemotherapy cycles. All were discharged after completion of chemotherapy if clinically stable. Patients were re-admitted for fever and discharged on empiric antibiotics if afebrile with negative cultures. Prophylactic antibiotics were administered in 55 cycles. There were 12 infections in 11 patients and no deaths due to infection. Patients remained outpatient for a mean of 15.8 neutropenia days per cycle. Outpatient supportive care for children with AML may be feasible and safe. Further studies are needed to establish outpatient supportive care guidelines.

Background/Purpose : Upadacitinib (UPA), an oral selective JAK1 inhibitor, has demonstrated favorable efficacy and acceptable safety in five Phase 3 global studies in patients with moderately to severely active rheumatoid arthritis (RA). 1-5 This analysis reports the efficacy and safety of UPA in predefined RA patient subgroups based on differences in baseline demographics and disease activity. Methods : Data were pooled from three pivotal, double-blind, PBO-controlled, multicenter, Phase 3 studies in patients with RA who had an inadequate response (IR) to conventional synthetic DMARDs (csDMARD-IR: SELECTNEXT [N=661]), MTX (MTX-IR; SELECT-COMPARE [N=1629]), or biologic DMARDs (bDMARD-IR: SELECT-BEYOND [N=498]). Two integrated analysis sets were evaluated: one comparing UPA 15 mg QD vs PBO (SELECT-NEXT, SELECT-COMPARE, SELECT-BEYOND) and the other comparing UPA 15 mg QD and UPA 30 mg QD vs PBO (SELECT-NEXT, SELECT-BEYOND). All patients received background treatment with csDMARDs. The proportion of patients achieving ACR20 and DAS28(CRP) <=3.2 at Week 12 was evaluated by predefined baseline demographics and disease activity measure groups, including age, sex, weight, BMI, race, geographic region, duration of RA, RF, and ACPA status, and level of high sensitivity CRP. Non-responder imputation was used for missing data. Subgroup analyses for safety were performed for age, race, sex, weight, BMI, and Asian region. Results : Across the three Phase 3 studies, 1036, 384, and 1041 patients received UPA 15 mg QD, UPA 30 mg QD or PBO, respectively. The demographic and baseline disease characteristics in the two integrated analysis sets were balanced across treatment groups. ACR20 and DAS28 <=3.2 response rates at Week 12 were consistently higher with UPA 15 mg and UPA 30 mg vs PBO across the evaluated demographic and baseline disease characteristics (Table). The efficacy of UPA 15 mg QD was generally similar to that observed with UPA 30 mg QD. At 12 weeks, the proportion of patients with treatment-emergent AEs, serious AEs, severe AEs, and AEs leading to discontinuation were generally comparable across different age, sex, race, weight, and BMI groups. Compared with the global population, patients receiving UPA in the Asian region had a higher rate of CPK elevations (UPA 30 mg only) and herpes zoster; herpes zoster also has been observed to be higher in the Asian region with other JAK inhibitors. 6,7 Conclusion : In this analysis of pooled integrated efficacy data in csDMARD-IR or bDMARD-IR patients with RA, UPA 15 mg or 30 mg QD in combination with csDMARDs improved efficacy outcomes at Week 12 when compared with PBO across all predefined subgroups evaluated. (Table Presented)

BACKGROUND:Autoimmune cytopenias are characterized by immune-mediated destruction of hematopoietic cell lines with immune thrombocytopenia (ITP) affecting platelets and Evans syndrome (ES) affecting platelets and red blood cells. For patients with persistent disease, limited options for effective and well-tolerated therapies exist. OBJECTIVES/OBJECTIVE:Our aim is to describe our institution's experience with sirolimus as therapy for pediatric patients with persistent ITP and ES. DESIGN/METHOD/METHODS:A retrospective analysis was performed in patients with persistent ITP and ES treated with sirolimus. Responses were categorized as complete response (CR), partial response, modest response, or no response. RESULTS:Of the 17 patients treated, 12 had ITP and 5 had ES. Seventy-three percent of ITP patients achieved a CR, 78% of them by 3 months. Only 2 patients did not achieve a durable response. Eighty percent of ES patients had a response, with 50% of them achieving CR and the other 50% an asymptomatic partial response. One patient with ES achieved modest response, but discontinued therapy due to an adverse effect. Of the patients that achieved CR, 90% remain off all therapy for a median of 2 years. CONCLUSIONS:Our data suggest that sirolimus is a safe and effective steroid-sparing agent in the treatment of persistent ITP and ES.

OBJECTIVES: To evaluate patterns of relapse and outcome in patients newly diagnosed with CNS Mixed Malignant GCT (MMGCT) treated initially with chemotherapy alone. METHODS: A retrospective chart review was conducted using all 25 patients enrolled on the International CNS GCT Study III, with at least 7 years follow-up for all surviving patients. RESULTS: Thirteen patients at diagnosis had CNS MMGCT by pathology and tumor markers (n = 11), or tumor markers alone (n = 2). Twelve received chemotherapy alone, one additionally receiving focal irradiation prior to relapse. Six patients (46%) relapsed (mean of 30.5 months; range 6-59 months), two beyond and four within the primary site alone. Three patients relapsed early (6-23 months from diagnosis), two with alpha-fetoprotein elevations and one without tumor markers assessed; all three expired of progressive disease at 2-10 months following initial relapse. Three patients relapsed late (37-59 months) without AFP elevations, one with pathologically pure germinoma, two with mild beta-human chorionic gonadotropin elevations; these patients survive disease-free at 86+, 94+, and 126+ months following additional treatment. CONCLUSIONS: Patients with CNS MMGCT relapsing following chemotherapy alone display two distinct patterns of recurrence and outcome; patients relapsing early possess MMGCT elements and have a dismal prognosis, while patients relapsing late do so with pure germinomatous elements and have an excellent outcome. Current cooperative group studies utilizing more localized fields of irradiation should monitor closely the patterns of relapse and outcome; late recurrences with germinomatous elements might be avoided by initial use of low-dose larger field irradiation in select patients. Pediatr Blood Cancer (c) 2015 Wiley Periodicals, Inc.

Objectives: To evaluate patterns of relapse and outcome in patients newly-diagnosed with CNS 'secreting' (or Mixed Malignant) GCT treated initially with chemotherapy without irradiation on the International CNS GCT Study III. Methods: A retrospective chart review was conducted using all 25 patients enrolled on the International CNS GCT Study III, with at least 7 years follow-up for all patients. Details of the chemotherapy regimen have been published previously (DaSilva et al: Pediatric Blood & Cancer, 54:337-383, 2010). Results: Thirteen patients at diagnosis had 'secreting' CNS GCT by pathology and tumor markers (n=11) or tumor markers alone (n=2). Twelve were treated with chemotherapy alone, one receiving focal irradiation following chemotherapy prior to relapse. Six patients (46%) relapsed (mean of 30.5 months; range 6 to 59 months), two beyond and 4 within the primary site alone. Three patients relapsed 'early' (between 6 and 23 months from diagnosis), 2 with alpha-fetoprotein (AFP) elevations and one without tumor markers assessed; all 3 expired of progressive disease at 2-10 months following initial relapse. Three patients relapsed 'late' (between 37 and 59 months), all without AFP elevations, one with pathologically-pure germinoma, two with mild beta-human chorionic gonadotropin elevations (<20mIU/mL in serum/cerebro-spinal fluid); these patients survive disease-free at 86+, 94+ and 126+ months following additional chemotherapy and irradiation. Conclusions: Patients with CNS 'secreting' tumors who relapse following chemotherapyonly regimens display two distinct patterns of recurrence and outcome; patients relapsing 'early' appear to possess 'secreting' elements and have a dismal prognosis, while patients relapsing 'late' appear to do so with pure germinomatous elements and have an excellent outcome. Current international cooperative group studies utilizing more localized fields of irradiation should evaluate closely the patterns of relapse and outcome; late recurrences with germinomatou!