Analysis of the Effect of Race, Socioeconomic Status, and Center Size on Unrelated National Marrow Donor Program Donor Outcomes: Donor Toxicities Are More Common at Low-Volume Bone Marrow Collection Centers

Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index (BMI), and age in unrelated donors undergoing collection at National Marrow Donor Program (NMDP) centers. We hypothesized that other important factors (race, socioeconomic status (SES), and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2,726 bone marrow (BM) and 6,768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week post donation (p=0.017). For BM donors, black males reported significantly higher levels of pain (OR=1.90, CI=1.14-3.19, p=0.015). No differences were noted by SES groups. BM donors from low volume centers reported more toxicity (OR=2.09, CI=1.26-3.46, p=0.006). In conclusion, race and SES have a minimal effect on donation associated symptoms. However, donors from centers performing ≤1 BM collection every 2 months have more symptoms following BM donation. Approaches should be developed by registries and low volume centers to address this issue

Robust Registration of Statistical Shape Models for Unsupervised Pathology Annotation

We present a method to automatically label pathologies in volumetric medical data. Our solution makes use of a healthy statistical shape model to label pathologies in novel targets during model fitting. We achieve this using an EM algorithm: the E-step classifies surface points into pathological or healthy classes based on outliers in predicted correspondences, while the M-step performs probabilistic fitting of the statistical shape model to the healthy region. Our method is indepen- dent of pathology type or target anatomy, and can therefore be used for labeling different types of data. The method is able to detect pathologies with higher accuracy than standard robust detection algorithms, which we show using true positive rate and F1 scores. Furthermore, the method provides an estimate of the uncertainty of the synthesized label. The detection also directly improves surface reconstruction results, as shown by a decrease in the average and Hausdorff distances to ground truth. The method can be used for automated diagnosis or as a pre-processing step to accurately label large amounts of images

3D Mapping of Serial Histology Sections with Anomalies Using a Novel Robust Deformable Registration Algorithm

The neuroimaging field is moving toward micron scale and molecular features in digital pathology and animal models. These require mapping to common coordinates for annotation, statistical analysis, and collaboration. An important example, the BRAIN Initiative Cell Census Network, is generating 3D brain cell atlases in mouse, and ultimately primate and human. We aim to establish RNAseq profiles from single neurons and nuclei across the mouse brain, mapped to Allen Common Coordinate Framework (CCF). Imaging includes (Forumala Presented). 500 tape-transfer cut 20 (Forumala Presented). m thick Nissl-stained slices per brain. In key areas 100 $$\upmu $$ m thick slices with 0.5–2 mm diameter circular regions punched out for snRNAseq are imaged. These contain abnormalities including contrast changes and missing tissue, two challenges not jointly addressed in diffeomorphic image registration. Existing methods for mapping 3D images to histology require manual steps unacceptable for high throughput, or are sensitive to damaged tissue. Our approach jointly: registers 3D CCF to 2D slices, models contrast changes, estimates abnormality locations. Our registration uses 4 unknown deformations: 3D diffeomorphism, 3D affine, 2D diffeomorphism per-slice, 2D rigid per-slice. Contrast changes are modeled using unknown cubic polynomials per-slice. Abnormalities are estimated using Gaussian mixture modeling. The Expectation Maximization algorithm is used iteratively, with E step: compute posterior probabilities of abnormality, M step: registration and intensity transformation minimizing posterior-weighted sum-of-square-error. We produce per-slice anatomical labels using Allen Institute’s ontology, and publicly distribute results online, with several typical and abnormal slices shown here. This work has further applications in digital pathology, and 3D brain mapping with stroke, multiple sclerosis, or other abnormalities

Donor Experiences of Second Marrow or Peripheral Blood Stem Cell Collection Mirror the First, but CD34 + Yields Are Less

Little is known about the experiences of individuals donating peripheral blood stem cells (PBSCs) or marrow for a second time. To study this, unrelated donors making a second donation through the National Marrow Donor Program between 2004 and 2013 were evaluated. Experiences of second-time donors giving marrow (n = 118: first donation was PBSC in 76 and marrow in 42) were compared with those making only 1 marrow donation (n = 5829). Experiences of second-time donors giving PBSCs (n = 602) (first donation was PBSCs in 362; marrow in 240) were compared to first-time PBSC donors (n = 16,095). For donors giving a second PBSC or marrow donation there were no significant differences in maximum skeletal pain, maximum symptoms measured by an established modified toxicity criteria, and recovery time compared with those who donated only once. Notably, the yield of marrow nucleated cells and PBSC CD34 cells with second donations was less. As previously noted with single first-time donations, female (PBSCs and marrow) and obese donors (PBSCs) had higher skeletal pain and/or toxicity with a second donation. PBSC donors who experienced high levels of pain or toxicity with the first donation also experienced high levels of these symptoms with their second donation and slower recovery times. In conclusion, for most donors second donation experiences were similar to first donation experiences, but CD34 yields were less. Knowledge of the donor's first experience and stem cell yields may help centers decide whether second donations are appropriate and institute measures to improve donor experiences