Necrotizing enterocolitis (NEC) is a leading cause of mortality among preterm infants with case-fatality rates of 20% to 30%.^1-3 The pathogenesis of NEC remains unclear with conflicting data regarding the role of 2 risk factors, red blood cell (RBC) transfusion and anemia, on the development of NEC. A meta-analysis of retrospective observational studies demonstrated an association between exposure to RBC transfusion and NEC, with receipt of RBC transfusion being associated with an increased risk of NEC (adjusted odds ratio, 2.0 [95% CI, 1.6-2.5]).⁴ However, more recent observational studies have found no association between RBC transfusion and NEC^5,6 or have found RBC transfusion to be protective.^7,8 In addition, a meta-analysis of randomized trials reported no difference in the incidence of NEC between infants receiving conservative vs liberal RBC transfusion approaches (pooled odds ratio, 1.67 [95% random-effects CI, 0.82-3.38]).⁹

Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had “recovered” (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell–associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.

PURPOSE: To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non–clear-cell renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients had advanced non–clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response. RESULTS: A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n = 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n = 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included NF2 and FH in cohort 1 and TP53 and PTEN in cohort 2. Objective responses were seen in 10/12 patients with either NF2 or FH mutations. CONCLUSION: Cabozantinib plus nivolumab showed promising efficacy in most non–clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non–clear-cell RCC variants warrant further study as predictors of response.

Importance Identification of patients with hereditary renal cell carcinoma (RCC) is important for cancer screening and, in patients with advanced disease, for guiding treatment. The prevalence of cancer-related germline mutations in patients with advanced RCC and the phenotypes associated with some rare mutations are unknown. Objectives To examine the prevalence of germline mutations in both known RCC predisposition genes and other cancer-associated genes and to identify clinical and pathologic factors associated with germline mutations. Design, Setting, and Participants In this cohort study conducted from October 1, 2015, to July 31, 2017, 254 of 267 patients with advanced (American Joint Committee on Cancer stage III or IV) RCC who were seen in medical oncology or urology clinics agreed to germline sequencing and disclosure of results under an institutional protocol of matched tumor-germline DNA sequencing. Main Outcomes and Measures Mutation prevalence and spectrum in patients with advanced RCC were determined. Clinical characteristics were assessed by mutation status. Results Of the 254 patients (median age [range], 56 [13-79] years; 179 [70.5%] male; 211 [83.1%] non-Hispanic white), germline mutations were identified in 41 (16.1%); 14 (5.5%) had mutations in syndromic RCC-associated genes (7 inFH, 3 inBAP1, and 1 each inVHL,MET,SDHA,andSDHB). The most frequent mutations wereCHEK2(n = 9) andFH(n = 7). Of genes not previously associated with RCC risk,CHEK2was overrepresented in patients compared with the general population, with an odds ratio of RCC of 3.0 (95% CI, 1.3-5.8;P = .003). Patients with non–clear cell RCC were significantly more likely to have an RCC-associated gene mutation (9 [11.7%] of 74 vs 3 [1.7%] of 177;P = .001), and 8 (10.0%) had a mutation in a gene that could guide therapy. Of patients with mutations in RCC-associated genes, 5 (35.7%) failed to meet current clinical guidelines for genetic testing. Conclusions and Relevance Of patients with non–clear cell RCC, more than 20% had a germline mutation, of which half had the potential to direct systemic therapy. Current referral criteria for genetic testing did not identify a substantial portion of patients with mutations, supporting the role of a more inclusive sequencing approach.

Transfusion-transmitted cytomegalovirus (TT-CMV) and breast milk–transmitted CMV (BM-CMV) infections can cause serious morbidity and mortality in immunologically immature, very low-birth-weight (VLBW) infants (birth weight, ≤1500 g). Transfusion of CMV-seronegative and/or leukoreduced blood components is a common strategy used to prevent TT-CMV; however, studies^1-3 conducted to validate this approach were small and yielded imprecise estimates of TT-CMV risk. Many of these studies^1-3 did not address factors associated with breakthrough cases of TT-CMV including leukoreduction quality control (linked to white blood cell filter failures and CMV transmission) and donor window period infections (when immunologically based assays may not detect CMV viremia).⁴ Additionally, studies of TT-CMV have not systematically evaluated BM-CMV, which may confound identification of the source of the infection. The burden of BM-CMV in VLBW infants has not been well quantified.⁵ Other, less common, sources of CMV in this population are genital secretion from CMV-seropositive mothers and community-acquired transmission.^6,7