Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL

PURPOSE CD19-targeted chimeric antigen receptor T cells (CD19-CAR) and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes. PATIENTS AND METHODS We conducted a multicenter, retrospective review of children and young adults with relapsed or refractory ALL who received CD19-CAR between 2012 and 2019. Primary objectives addressed 6-month relapse-free survival (RFS) and event-free survival (EFS), stratified by blinatumomab use. Secondary objectives included comparison of longer-term survival outcomes, complete remission rates, CD19 modulation, and identification of factors associated with EFS. RESULTS Of 420 patients (median age, 12.7 years; interquartile range, 7.1-17.5) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR constructs, 77 (18.3%) received prior blinatumomab. Blinatumomab-exposed patients more frequently harbored KMT2A rearrangements and underwent a prior stem-cell transplant than blinatumomab-naïve patients. Among patients evaluable for CD19-CAR response (n = 412), blinatumomab nonresponders had lower complete remission rates to CD19-CAR (20 of 31, 64.5%) than blinatumomab responders (39 of 42, 92.9%) or blinatumomab-naive patients (317 of 339, 93.5%), P < .0001. Following CD19-CAR, blinatumomab nonresponders had worse 6-month EFS (27.3%; 95% CI, 13.6 to 43.0) compared with blinatumomab responders (66.9%; 95% CI, 50.6 to 78.9; P < .0001) or blinatumomab-naïve patients (72.6%; 95% CI, 67.5 to 77; P < .0001) and worse RFS. High-disease burden independently associated with inferior EFS. CD19-dim or partial expression (preinfusion) was more frequently seen in blinatumomab-exposed patients (13.3% v 6.5%; P = .06) and associated with lower EFS and RFS. CONCLUSION With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high-disease burden were independently associated with worse RFS and EFS, identifying important indicators of long-term outcomes following CD19-CAR.

Immediate Intravenous Epinephrine (Within 1-minute) Versus Early Intravenous Epinephrine (After 1-minute) for In-Hospital Cardiopulmonary Arrest: A Multicenter Retrospective Review

Background: intravenous epinephrine has been a key treatment for cardiopulmonary arrest since the early 1960s. Although, many studies have questioned neurological outcome benefit, it remains to be recommended in international guidelines for its benefit on return of spontaneous circulation (ROSC). The ideal timing for the first epinephrine dose is uncertain. We aimed to look at the association of immediate epinephrine administration (within 1-minute of cardiac arrest recognition) with return of spontaneous circulation (ROSC) up to 24-hours and beyond 24-hours.Methods: this was a multicenter retrospective chart review of patients undergoing cardiopulmonary resuscitation.Results: immediate epinephrine administration (within 1-minute) is associated with higher rates of ROSC up to 24-hours (OR=2.36, 95% CI; [1.46-3.81]) and beyond 24-hours (OR=2.26, 95% CI; [1.06-4.83]).Conclusions: we encourage immediate administration of epinephrine in conjunction with high-quality CPR, as this is associated with higher rates of ROSC.

Prenatal Imaging Diagnosis of Suprarenal Lesions

Introduction: Prenatal suprarenal lesions represent diverse pathologies. This study investigated prenatal imaging features and regression patterns associated with specific lesion diagnoses. Methods: This is a multicenter retrospective review of fetuses with prenatally diagnosed suprarenal lesions between 2001 and 2019. Prenatal ultrasound and MRI characteristics, postnatal imaging, and clinical course were reviewed. Prenatal imaging findings were compared by the most common diagnoses and regression patterns. Results: Forty-four fetuses were prenatally diagnosed with suprarenal lesions. Diagnoses included pulmonary sequestration (n = 12; 27.3%), adrenal hemorrhage (n = 12; 27.3%), upper quadrant cyst (including 2 duplication cysts, 1 splenic cyst, and 3 indeterminate cysts), neuroblastoma (n = 4), adrenal hyperplasia (n = 3), bilateral adrenal calcifications (n = 1), and indeterminate lesions (n = 6). Sequestrations were uniformly left-sided (100 vs. 50%; p = 0.014) and diagnosed earlier in gestation than adrenal hemorrhages (p = 0.025). Sequestrations were also significantly more likely to have a prenatal feeding vessel (p = 0.005), low T1 MRI signal (p = 0.015), and no MRI blood products (p = 0.018) compared to adrenal hemorrhages. When comparing all 44 patients, a prenatal feeding vessel and low T1 signal on prenatal MRI were significantly associated with lesion persistence (p = 0.003; p = 0.044). Discussion/Conclusion: Imaging findings on prenatal ultrasound and MRI aid in the diagnosis of suprarenal lesions, including differentiating pulmonary sequestrations and adrenal hemorrhages.

Analysis of retinopathy of prematurity screening in Tianjin, China

AIM: To analyze the findings of retinopathy of prematurity (ROP) exam in Tianjin, and study the impact of pulmonary surfactant Curosurf and nasal continuous positive airway pressure (NCPAP) in ROP. METHODS: A multicenter retrospective review. 2894 preterm infants (1592 males, 1302 females) from several hospitals in Tianjin were screened from January 2009 to December 2013. Demographic information, ophthalmic outcomes and possible systemic risk factors were recorded. Gestation age, birth weight, oxygen supplementation, Curosurf and NCPAP were used to estimate risk factors for ROP. RESULTS: ROP was found in 448 eyes of 224 patients (7.7%). Among which, severe ROP developed in 98 eyes of 49 patients (21.9%). There was significant statistical difference in RDS, NCPAP, and Curosurf usage between control and ROP groups (P=0.000). Multiple logistic regression analyses of ROP indicated that lower birth weight, younger gestational age, and oxygen supplementation were the risk factors leading to ROP. As the usage rate of Curosurf and NCPAP increased year by year, the usage of oxygen supplementation gradually decreased, the incidence of ROP was also on the decline. CONCLUSION: Low birth weight, young gestational age and oxygen supplementation are associated with ROP. The use of Curosurf and NCPAP may be the factor that reduces the occurrence of ROP.