Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study.

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor v no donor) study. METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with TP53 mutations were classified as TP53multihit if two alleles were altered (via point mutation, deletion, or copy-neutral loss of heterozygosity). RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with TP53 (28% v 29%; P = .89), ASXL1 (23% v 29%; P = .37), and SRSF2 (16% v 16%; P = .99) being most common. OS in patients with a TP53 mutation was worse compared with patients without TP53 mutation (21% ± 5% [SE] v 52% ± 4% at 3 years; P < .001). Among those with a TP53 mutation, OS was similar between TP53single versus TP53multihit (22% ± 8% v 20% ± 6% at 3 years; P = .31). Considering HCT as a time-dependent covariate, patients with a TP53 mutation who underwent HCT had improved OS compared with non-HCT treatment (OS at 3 years: 23% ± 7% v 11% ± 7%; P = .04), associated with a hazard ratio of 3.89; 95% CI, 1.87 to 8.12; P < .001 after adjustment for covariates. OS among patients with molecular IPSS (IPSS-M) very high risk without a TP53 mutation was significantly improved if they had a donor (68% ± 10% v 0% ± 12% at 3 years; P = .001). CONCLUSION: HCT improved OS compared with non-HCT treatment in patients with TP53 mutations irrespective of TP53 allelic status. Patients with IPSS-M very high risk without a TP53 mutation had favorable outcomes when a donor was available.

Measurable Residual IDH1 before Allogeneic Transplant for Acute Myeloid Leukemia.

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3-ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1, at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants (IDH1m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1-mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3-ITD, only detection of persistent mutated NPM1 and/or FLT3-ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk.

The role of enhanced recovery after surgery protocols in the development of acute kidney injury following radical cystectomy.

PURPOSE: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center. MATERIALS AND METHODS: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI. RESULTS: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16). CONCLUSION: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center.

Comparing Pathologic and Survival Outcomes Between Primary and Secondary Muscle Invasive Bladder Cancer When Treated by Radical Cystectomy With or Without Neoadjuvant Chemotherapy.

OBJECTIVE: To compare pathologic and survival outcomes between primary muscle invasive (pMIBC) and secondary muscle invasive (sMIBC) bladder cancer patients who were treated with or without cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We reviewed cT2-T4/N0 MIBC patients at our institution between 2010-2019. pMIBC was defined as presenting with > cT2 disease on initial or restaging TURBT with no prior history of bladder cancer. sMIBC was defined as prior history of NMIBC that was treated with at least one induction course of BCG that progressed to MIBC. Outcomes analyzed included pathologic downstaging rates defined as pT2 and N+ disease were predictors of poorer CSS and OS. Separate analysis of sMIBC patients whom underwent RC only (N = 61), demonstrated inferior oncologic outcomes to other cohorts (P < .01). CONCLUSION: There were no differences in pathologic response or survival between pMIBC and sMIBC patients when managed with NAC and RC.

Ability of the surgical Apgar score to predict acute kidney injury following radical cystectomy.

PURPOSE: Acute kidney injury (AKI) is a common complication after radical cystectomy (RC). Previous literature has shown that intraoperative hemodynamic instability measured via the surgical Apgar score is an independent predictor of major complications following RC. We sought to determine whether the surgical Apgar score is predictive of postoperative AKI. METHODS: We performed a retrospective review of RC patients at our institution from 2010 to 2017. Intraoperative hemodynamic instability was captured via the Apgar score based on the lowest intraoperative mean arterial blood pressure, lowest heart rate, and estimated blood loss. Patients were divided into 3 groups: high-risk (HR; Apgar ≤4), intermediate-risk (IR; Apgar score 5-6), and low-risk (LR; Apgar score ≥7). AKIs were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. High grade AKIs were defined as KDIGO grade 2 or 3. Categorical variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test, and multivariable logistic regression to identify predictors of AKI and high grade AKIs within 30 days of RC. RESULTS: Eight hundred and seventy-three patients were included with a median follow-up of 35 months. AKI within 30 days was observed in 28% of patients. Predictors of AKI within 30 days on adjusted analysis included IR (OR: 1.83, P = 0.002) and HR (OR: 3.53, P < 0.001) Apgar scores. IR (OR: 2.23, P = 0.007) and HR (OR: 4.87, P < 0.001) Apgar scores were also predictors of high-grade AKIs. CONCLUSION: Intraoperative hemodynamic instability measured via the Apgar score can be predictive of AKI, which can guide individualized fluid management in the postoperative period.