Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non–first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell–replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non–first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives.     

Sagittal abdominal diameter and waist circumference appear to be equally good as identifiers of cardiometabolic risk

Background and aimsBody mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed as a possibly more sensitive marker of intra-abdominal obesity. We investigated differences in how SAD, WC, and BMI were correlated with cardiometabolic risk markers.Methods and resultsThis cross-sectional study investigated anthropometric and metabolic baseline measurements of individuals from six trials. Multiple linear regression and (partial) correlation coefficients were used to investigate associations between SAD, WC, and BMI and cardiometabolic risk markers, including components of the metabolic syndrome as well as insulin resistance, blood lipids, and lowgrade inflammation.In total 1516 mostly overweight or obese individuals were included in the study. SAD was significantly more correlated with TG than WC for all studies, and overall increase in correlation was 0.05 (95% CI (0.02; 0.08). SAD was significantly more correlated with the markers TG and DBP 0.11 (95% CI (0.08, 0.14)) and 0.04 (95% CI (0.006, 0.07), respectively compared to BMI across all or most studies.ConclusionThis study showed that no single anthropometric indicator was consistently more strongly correlated across all markers of cardiometabolic risk. However, SAD was significantly more strongly correlated with TG than WC and significantly more strongly correlated with DBP and TG than BMI.     

A standardized framework for the validation and verification of clinical molecular genetic tests

The validation and verification of laboratory methods and procedures before their use in clinical testing is essential for providing a safe and useful service to clinicians and patients. This paper outlines the principles of validation and verification in the context of clinical human molecular genetic testing. We describe implementation processes, types of tests and their key validation components, and suggest some relevant statistical approaches that can be used by individual laboratories to ensure that tests are conducted to defined standards.     

The development and initial validation of the narrative foreclosure scale

Objectives: As people grow older, identity development in later life becomes a more and more relevant topic. Studying processes that hinder or promote identity development in later life is of importance. Within this broader field, there has been a growing interest in narrative foreclosure. Our goal was to develop a short, reliable and easy–to-use instrument measuring narrative foreclosure and to validate this instrument in two samples.Methods: The narrative foreclosure scale (NFS) was validated in two studies with a sample of middle-aged adults (n = 319) and a sample with older adults (n = 174). Several analyses were conducted to assess the psychometric properties, the factor-structure and incremental validity of the scale.Results: Confirmatory factor analyses generally showed an acceptable fit of the two-factor (NF-Future and NF-Past) model to the data in both samples. Both factors of the NFS demonstrated adequate to good internal consistency, with alpha coefficients ranging from .79 for NF-Past in study 2 to .88 for NF-Future in study 1. Construct validity was good as shown by moderate to large correlations to related constructs. The scale adds a unique portion of explained variance to positive mental health, thereby showing the incremental validity of the NFS.Conclusion: A reliable scale is now available that allows to study the premature hindering of identity development in older populations. The use of the NFS as a process measure in studies on the effectiveness of interventions aiming at meaning making and identity development, such as life-review therapy and narrative therapy, is also recommended.     

EGFR related mutational status and association to clinical outcome of third-line cetuximab-irinotecan in metastatic colorectal cancer

Background  

As supplement to KRAS mutational analysis, BRAF and PIK3CA mutations as well as expression of PTEN may account for additional non-responders to anti-EGFR-MoAbs treatment. The aim of the present study was to investigate the utility as biomarkers of these mutations in a uniform cohort of patients with metastatic colorectal cancer treated with third-line cetuximab/irinotecan.     

Potential of dose optimisation in MRI-based PDR brachytherapy of cervix carcinoma

BACKGROUND AND PURPOSE: In this study on PDR treatment planning of utero-vaginal carcinoma, we analysed the dosimetry of traditional X-ray based plans as it presents on MR images. The potential gain of MRI-based dose optimisation was assessed. PATIENTS AND METHODS: Sixteen patients boosted with PDR brachytherapy after external beam therapy were included. The clinical X-ray based plans were projected on MR images. The GTV, HR-CTV and IR-CTV were retrospectively contoured, as well as the bladder, rectum and sigmoid colon. The dose in the critical organs and target coverage was investigated. In a second phase, the plans were manually optimised using the MR information. The objectives were to lower the dose in the critical organs (85Gy(alphabeta3) for bladder, 75Gy(alphabeta3) for rectum and sigmoid colon) and to increase the HR-CTV dose to D9085Gy(alphabeta10). RESULTS: In the X-ray based plans, D(2cc) in bladder and sigmoid colon exceeded the tolerance doses in 10/16 and 7/16 patients, respectively. Coverage of the IR-CTV with the 60Gy(alphabeta10) was acceptable. D90 of the HR-CTV was below 85Gy(alphabeta10) in 13 out of 16 patients. After optimisation, the dose constraints in the OAR were not exceeded anymore in any patient. The average D(2cc) dose reduction was 7+/-6Gy(alphabeta3) in the bladder and 7+/-4Gy(alphabeta3) in the sigmoid colon for those patients in which the dose constraint was initially exceeded. In addition, an average dose increase of 3Gy(alphabeta10) was accomplished in the HR-CTV. CONCLUSIONS: MRI-based dose optimisation can play an important role to reduce the dose delivered to the critical organs and to improve target coverage.