Citations

Abstract Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.

Abstract Background Axitinib is an oral small molecule that inhibits receptor tyrosine kinases vascular endothelial growth factor receptors 1 to 3. A phase 1 and pharmacokinetic (PK) trial evaluating axitinib was conducted in children with refractory solid tumors. Methods Axitinib was administered orally twice daily in continuous 28‐day cycles. Dose levels (2.4 mg/m 2 /dose and 3.2 mg/m 2 /dose) were evaluated using a rolling 6 design. Serial PKs (cycle 1, days 1 and 8) and exploratory biomarkers were analyzed. Results A total of 19 patients were enrolled; 1 patient was ineligible due to inadequate time having elapsed from prior therapy. The median age of the patients was 13.5 years (range, 5‐17 years). Two of 5 patients who were treated at dose level 2 experienced dose‐limiting toxicities (palmar‐plantar erythryodysesthesia syndrome in 1 patient and intratumoral hemorrhage in 1 patient). Frequent (>20%) grade 1 to 2 toxicities during cycle 1 included anemia, anorexia, fatigue, diarrhea, nausea, and hypertension. Nonhematological toxicities of grade ≥3 in subsequent cycles included hypertension and elevated serum lipase. PK analysis demonstrated variability in axitinib exposure, the median time to peak plasma concentration was 2 hours, and the half‐life ranged from 0.7 to 5.2 hours. Exposure and dose were not found to be significantly associated with hypertension. Five patients achieved stable disease for ≥6 cycles as their best response, including patients with malignant peripheral nerve sheath tumor (1 patient), Ewing sarcoma (1 patient), hepatocellular carcinoma (1 patient), and osteosarcoma (2 patients). One patient with alveolar soft part sarcoma achieved a partial response. Kidney injury biomarkers were found to be elevated at baseline; no trends were identified. Conclusions In children with refractory solid tumors, the maximum tolerated and recommended dose of axitinib appears to be 2.4 mg/m 2 /dose, which provides PK exposures similar to those of adults.

AbstractBackgroundThe study aims were to model acute pain intensity and opioid consumption trajectories up to 72 hr after open hepatic resection, identify predictors of trajectory membership and examine the association between trajectory memberships and 6‐month pain and psychological outcomes. This is a long‐term analysis of a published randomized controlled trial on the impact of medial open transversus abdominis plane catheters on post‐operative outcomes.MethodsA total of 152 patients (89 males; mean age 63.0 [range: 54–72]) completed questionnaires on pain and related characteristics pre‐operatively and 6 months post‐operatively. Total opioid use was recorded several times over a 72‐hr period while self‐reported pain intensity scores were collected multiple times until hospital discharge. Analyses were carried out using growth mixture modelling, logistic regression and general linear models.ResultsBoth pain intensity and opioid consumption showed that a four‐trajectory model best fits the data. Patients in the lowest opioid consumption trajectory were more likely to be classified in the constant mild pain intensity trajectory. Age and baseline levels of anxiety significantly predicted opioid trajectory membership while baseline depressive symptoms significantly predicted pain intensity trajectory membership. Patients in the two highest opioid consumption trajectories reported significantly higher levels of pain catastrophizing at 6 months compared to patients in the other 3 trajectories (all p < 0.05).ConclusionHigh consumption of opioids after surgery is associated with higher levels of pain catastrophizing 6 months later. Identification of patients within these trajectories may lead to the development of early interventions targeted to high risk individuals.SignificanceDifferences in initial levels of opioid consumption and rates of change in opioid consumption shortly after surgery can help predict long‐term psychological responses to pain. Identifying key characteristics associated with initial opioid consumption can lead to the development of cost‐effective early interventions targeted to high risk individuals.

SummaryObjectiveWe aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP).MethodsWe prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea–Sleep Disorders Questionnaire (SA‐SDQ) and STOP‐BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP‐7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed‐rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP‐7 scores.ResultsThirty‐five percent of patients had pOSA, with a mean ODI of 11.3 ± 5.1/h (range = 5.1‐22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA‐SDQ and STOP‐BAG scores (all P < 0.05). Median rSUDEP‐7 score was 3 ± 1.4 (range = 0‐6). Higher rSUDEP‐7 scores were positively correlated with higher ODI (P = 0.036). rSUDEP‐7 score ≥ 5 was associated with pOSA by ODI, SA‐SDQ, and STOP‐BAG questionnaire criteria (P < 0.05).SignificanceOur pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.

Background: A symptomatic discoid lateral meniscus is an uncommon orthopaedic abnormality, and the majority of information in the literature is limited to small case series. Purpose/Hypothesis: The purpose of this study was to determine the incidence of symptomatic discoid menisci in a geographically determined population and to describe treatment trends over time. The hypothesis was that the incidence of symptomatic discoid menisci would be highest among adolescent patients, and thus, the rate of surgical treatment would be high compared with nonoperative treatment. Study Design: Descriptive epidemiology study. Methods: The study population included 79 patients in Olmsted County, Minnesota, identified through a geographic database, who were diagnosed with a symptomatic discoid lateral meniscus between 1998 and 2015. The complete medical records were reviewed to confirm the diagnosis and evaluate the details of injury and treatment. Age- and sex-specific incidence rates were calculated and adjusted to the 2010 United States population. Results: The overall annual incidence of symptomatic discoid lateral menisci was 3.2 (95% CI, 2.5-3.9) per 100,000 person-years; 12.6% of the patients in the cohort had bilateral symptomatic discoid lateral menisci. The overall annual incidence was similar between male (3.5 per 100,000 person-years) and female patients (2.8 per 100,000 person-years). The highest incidence of symptomatic discoid lateral menisci was noted in adolescent male patients aged 15-18 years (18.8 per 100,000 person-years). A majority (72.2%) of patients presented with a symptomatic tear of the discoid meniscus. The remaining patients presented with mechanical symptoms, including catching/locking or effusion, with no demonstrable meniscus tear on imaging or diagnostic arthroscopic surgery. Additionally, 20.0% of patients were observed to have peripheral instability of the meniscus at the time of diagnostic arthroscopic surgery. The mean age of those with peripheral instability was significantly younger than of those who did not have peripheral instability. Sixty patients (75.9%) received surgical treatment during the study period, including 49 (81.7%) patients who underwent partial lateral meniscectomy and 11 (18.3%) patients who underwent lateral meniscus repair in addition to saucerization. Conclusion: With an overall annual incidence of 3.2 per 100,000 person-years, a symptomatic discoid meniscus is an uncommonly encountered orthopaedic abnormality. However, the incidence of symptomatic discoid lateral menisci is highest in adolescent male patients. Because of the high rate of meniscus tears in patients presenting with symptoms, the majority are treated surgically.

11503 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell subtype commonly found in the peripheral blood of patients in all stages of solid malignancies and in a variety of cancer subtypes. However, while their biological association to cancer is being studied, their clinical utilization as it relates to cancer prognosis has not been evaluated. Methods: A two year prospective study was undertaken to evaluate the relationship of CAMLs and overall survival (OS) in 6 solid tumor types. The single blind multi-institutional study consisted of 269 stage I-IV patients; breast (n = 57), esophageal (n = 21), prostate (n = 43), pancreatic (n = 59), lung (n = 54), and renal cell (n = 35), in treatment (n = 134) and untreated baseline (n = 135). 7.5mL of whole blood was filtered by CellSieve microfiltration assay and CAMLs enumerated, as previously described. Patients were grouped by CAML number ( < 6 or ≥6) and by size ( < 49 or ≥50 µm) to evaluate hazard ratios (HR) by censored univariate & multivariate analysis. Results: CAMLs were identified in 93% of samples, averaging 8.2 CAMLs/7.5mL blood sample, and found in all 6 cancers at baseline and during treatment. Average CAML number was associated with disease stage and CAML positivity was 4.4 & 80% (Stage I), 4.7 & 93% (Stage II), 9.3 & 98% (Stage 3), 12.1 & 97% (Stage IV). Univariate analysis of patients (n = 269) stratified by ≥6 CAMLs had reduced OS (HR = 1.8, 95%CI 1.1-2.9, p = 0.03). Further, CAML size also had reduced OS in patients with ≥50 µm CAMLs (HR = 2.7, 95%CI 1.8-4.0, p < 0.0001). Conclusions: Our data suggests that in solid malignancies, CAML number and size appear to clinically correlate with OS in early and late stage disease. Given these results relating CAMLs with OS, further analysis is warranted to determine if CAMLs can serve as a clinically-relevant blood-based marker.