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Background: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported. Methods: The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. We conducted a retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution. Results: There was a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n = 7), with four cases being severe AKI (stages 2–3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14 days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30 days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and cytokine release syndrome and neurotoxicity. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe. Conclusions: Frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population. [ABSTRACT FROM AUTHOR]

The need to model a cure fraction, the proportion of a cohort not susceptible to the event of interest, arises in a variety of contexts including tumor relapse in oncology. Existing methodology assumes that follow‐up is long enough for all uncured subjects to have experienced the event of interest at the time of analysis, and researchers have demonstrated that fitting cure models without sufficient follow‐up leads to bias. Few statistical methods exist to evaluate sufficient follow‐up, and they can exhibit poor performance and lead users to falsely conclude sufficient follow‐up, leading to bias, or to falsely claim insufficient follow‐up, possibly leading to additional, costly data collection. We propose a new quantitative statistic (RECeUS) to evaluate whether cure models may be appropriate to apply to censored data. Specifically, we propose that the estimated proportion of censored uncured subjects in a study can be used to evaluate cure model appropriateness. We evaluated the performance of RECeUS against existing methods via simulation and with two data examples, and we observe that RECeUS displays superior performance. In simulated and real‐world settings, RECeUS correctly identifies both situations in which data appear appropriate for cure modeling and when data seem inappropriate for fitting cure models. [ABSTRACT FROM AUTHOR]

Background: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. Methods: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. Results: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72–98) and 88% (95% CI: 67–96); ≥ CR2 were 81% (95% CI: 61–92) and 68% (95% CI: 47–82) and refractory disease were 32% (95% CI: 11–54) and 20% (95% CI: 6–40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64–87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/μL and 140/μL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). Conclusion: The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611). [ABSTRACT FROM AUTHOR]

The current approach for preventing hemolysis of red blood cells (RBCs) in major ABO-incompatible bone marrow (BM) grafts after infusion is to deplete RBCs from BM products before transplantation. Traditionally, manual density separation (MDS) using Ficoll-Hypaque (Cytiva Sweden AB, Uppsala, Sweden has been used to accomplish RBC depletion. This process yields good CD34+ cell recovery, but it requires open manipulation and is labor-intensive and time-consuming. We hypothesized that an alternative automated method using Haemonetics Cell Saver 5+ (Haemonetics Corporation, Boston, MA, USA) would offer equivalent RBC depletion and CD34+ cell recovery. Small marrow volumes from pediatric donors can be processed using Cell Saver (CS) without adding the third-party RBCs necessary for other automated methods. This retrospective analysis comprised data from 58 allogeneic BM grafts. RBC depletion and CD34+ cell recovery from BM using MDS (35 grafts) were compared with CS (14 grafts). Nine products underwent RBC depletion using CS with Ficoll (CS-F) when RBC volume was less than 125 mL. Linear regression analysis of log transformation of CD34+ cell recovery adjusted for log transformation of both baseline CD34+ cell content and baseline total volume showed no significant difference between MDS and CS (estimated coefficient, –0.121, P = 0.096). All products contained an RBC volume of less than 0.25 mL/kg post-processing. CD34+ cell recovery with CS-F was comparable to MDS and CS and suitable for pediatric recipients of allogeneic hematopoietic cell transplantation. We provide evidence that an automated method using Haemonetics Cell Saver 5+ achieves RBC depletion and CD34+ cell recovery comparable to MDS when adjusting for baseline factors. [ABSTRACT FROM AUTHOR]

Background: After colorectal cancer (CRC) surgery, surveillance with colonoscopy is an important step for the early detection of local recurrence. Unfortunately, surveillance colonoscopy is underused, especially among racial/ethnic minorities. This study assesses the association between patient and neighborhood factors and receipt of surveillance colonoscopy. Methods: This retrospective, population‐based cohort study used Surveillance, Epidemiology, and End Results–Medicare linked data (2009‐2014). Beneficiaries with surgically resected stage II or III CRC between the ages of 66 and 85 years were identified, and multivariable logistic regression was used to assess the effect of factors on receipt of colonoscopy. Results: Overall, 57.5% of the patients received initial surveillance colonoscopy. After adjustments for all factors, Blacks and Hispanics had lower odds of receiving colonoscopy than non‐Hispanic Whites (NHWs; 29.6% for Blacks; P =.002; 12.9% for Hispanics; P >.05). NHWs with Medicaid coverage had 35% lower odds of surveillance colonoscopy than NHWs without Medicaid coverage. Minority patients with Medicaid were more likely to receive colonoscopy than their racial/ethnic counterparts without Medicaid coverage (P >.05). Hispanics residing in neighborhoods with incomes of ≥$90,000 had significantly lower odds of surveillance colonoscopy than Hispanics residing in neighborhoods with incomes of $0 to $30,000. Conclusions: Receipt of initial surveillance colonoscopy remains low, and there are acute disparities between Black and NHW patients. The association between factors that assess a patient's ability to access colonoscopy and actual receipt of colonoscopy suggests inequitable access to surveillance colonoscopy within and across racial/ethnic groups. There are disparities in the receipt of initial surveillance colonoscopy between Black and non‐Hispanic White patients. The association between factors that assess a patient's ability to access colonoscopy and actual receipt of colonoscopy suggests inequitable access to surveillance colonoscopy within and across racial/ethnic groups. [ABSTRACT FROM AUTHOR]