Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL.

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P = .07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.

Characteristics and Outcomes of Long-Stay Patients in the Pediatric Intensive Care Unit.

Long-stay patients in the PICU have a higher risk of mortality as compared with non-long-stay patients. We aim to describe mortality and characteristics of long-stay patients and to determine the risk factors for mortality in these children. Total 241 (4.8%) long-stay admissions were identified. Mortality of long-stayers was 48/241 (20%). Higher severity-of-illness score at admission, need for organ support therapies, number of nosocomial infections, and bloodstream nosocomial infection were associated with a higher mortality in long-stay patients in the PICU. Based on multivariate analysis, oncologic diagnosis as a preexisting comorbidity is a strong independent predictor of mortality for long-stay patients.

Unusual presentation of myeloid sarcoma in a case of acute promyelocytic leukemia with a cryptic PML-RARA rearrangement involving multiple sites including the atrium.

Myeloid sarcoma is an extramedullary tumor mass composed of immature myeloid cells. Myeloid sarcoma may develop de novo, concurrently with acute myeloid leukemia (AML), or at relapse. Although myeloid sarcoma can occur at any site, myeloid sarcoma involving the heart is extremely rare. Reported here is the case of a 30-year-old man, initially diagnosed with acute promyelocytic leukemia (APL) in bone marrow, who presented later with myeloid sarcoma at multiple anatomical sites (left scapula, thoracic vertebra, right atrium, and supraclavicular mass) in multiple relapses. Conventional cytogenetic studies performed on the atrial sample revealed a karyotype with additional material on the short arm of chromosome 7, at 7p22. Fluorescence in situ hybridization studies confirmed a cryptic PML-RARA fusion on the short arm of chromosome 7, as well as a second fusion on one copy of chromosome 15. With the fourth and latest relapse, molecular cytogenetic studies performed on interphase nuclei of the myeloid sarcoma specimen (a supraclavicular mass) showed evidence of six related abnormal clones with a PML-RARA fusion, suggesting clonal evolution. This represents a rare case of APL with a cryptic PML-RARA rearrangement presenting as myeloid sarcoma at multiple relapses and involving multiple anatomical sites, including cardiac atrium.