Jennifer Crow

Donor Cell-Derived Leukemias/Myelodysplastic Neoplasms in Allogeneic Hematopoietic Stem Cell Transplant Recipients A Clinicopathologic Study of 10 Cases and a Comprehensive Review of the Literature

We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) showed donor gonosomal complements, suggesting DCL. Clonal cytogenetic abnormalities were detected in 8 cases: 6 were monosomy 7/del(7q). In all 10 cases, engraftment studies confirmed donor cell origin. Retrospective fluorescence in situ hybridization in archived donor cells in 4 cases showed a low level of abnormalities in 2. Of 7 patients with clinical follow-up of 5 months or more, 1 (with acute myeloid leukemia) died of disease; 6 are alive, including 1 with myelodysplastic syndrome with spontaneous remission. Similar to reported cases, we found disproportional sex-mismatched HCTs, suggesting probable underdetection of DCL in sex-matched HCTs. The latency between HCT and DCL ranged from 1 to 193 months (median, 24 months), in keeping with the literature. Analyzing our cases, pooled with reported cases, with survival models showed much shorter latency for malignancy as primary disease, for T-cell large granular lymphocyte leukemia as type of DCL, and for umbilical cord blood as stem cell source.

Bariatric Embolization for Suppression of the Hunger Hormone Ghrelin in a Porcine Model

PURPOSE To prospectively test in a porcine model the hypothesis that bariatric embolization with commercially available calibrated microspheres can result in substantial suppression of systemic ghrelin levels and affect weight gain over an 8-week period. MATERIALS AND METHODS The institutional animal care and use committee approved this study. Twelve healthy growing swine (mean weight, 38.4 kg; weight range, 30.3-47.0 kg) were evaluated. Bariatric embolization was performed by infusion of 40-μm calibrated microspheres selectively into the gastric arteries that supply the fundus. Six swine underwent bariatric embolization, while six control animals underwent a sham procedure with saline. Weight and fasting plasma ghrelin and glucose levels were obtained in animals at baseline and at weeks 1-8. Statistical testing for differences in serum ghrelin levels and weight at each time point was performed with the Wilcoxon signed rank test for intragroup differences and the Wilcoxon rank sum test for intergroup differences. RESULTS The pattern of change in ghrelin levels over time was significantly different between control and experimental animals. Weekly ghrelin levels were measured in control and experimental animals as a change from baseline ghrelin values. Average postprocedure ghrelin values increased by 328.9 pg/dL ± 129.0 (standard deviation) in control animals and decreased by 537.9 pg/dL ± 209.6 in experimental animals (P = .004). The pattern of change in weight over time was significantly different between control and experimental animals. The average postprocedure weight gain in experimental animals was significantly lower than that in control animals (3.6 kg ± 3.8 vs 9.4 kg ± 2.8, respectively; P = .025). CONCLUSION Bariatric embolization can significantly suppress ghrelin and significantly affect weight gain. Further study is warranted before this technique can be used routinely in humans.

Developing patient-friendly genetic and genomic test reports: formats to promote patient engagement and understanding

With the emergence of electronic medical records and patient portals, patients are increasingly able to access their health records, including laboratory reports. However, laboratory reports are usually written for clinicians rather than patients, who may not understand much of the information in the report. While several professional guidelines define the content of test reports, there are no guidelines to inform the development of a patient-friendly laboratory report. In this Opinion, we consider patient barriers to comprehension of lab results and suggest several options to reformat the lab report to promote understanding of test results and their significance to patient care, and to reduce patient anxiety and confusion. In particular, patients’ health literacy, genetic literacy, e-health literacy and risk perception may influence their overall understanding of lab results and affect patient care. We propose four options to reformat lab reports: 1) inclusion of an interpretive summary section, 2) a summary letter to accompany the lab report, 3) development of a patient user guide to be provided with the report, and 4) a completely revised patient-friendly report. The complexity of genetic and genomic test reports poses a major challenge to patient understanding that warrants the development of a report more appropriate for patients.

A clinical prediction tool to estimate the number of units of red blood cells needed in primary elective coronary artery bypass surgery

BACKGROUND: Red blood cell (RBC) transfusion is common during cardiac surgical procedures. Empiric crossmatching, without attempting to estimate individual transfusion requirements is typical. We hypothesized that a clinical prediction tool could be developed to estimate the number of units of RBCs needed for coronary artery bypass grafting (CABG) surgery.

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model.

OBJECTIVE Achieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model. METHODS Nine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 μm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied. RESULTS Calf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm. CONCLUSIONS Calf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system.

Donor Cell Leukemia in Umbilical Cord Blood Transplant Patients: A Case Study and Literature Review Highlighting the Importance of Molecular Engraftment Analysis

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patients original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patients diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patients disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patients presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.

Histopathologic and Immunohistochemical Sequelae of Bariatric Embolization in a Porcine Model

PURPOSE To evaluate the histopathologic sequelae of bariatric embolization on the gastric mucosa and to correlate with immunohistochemical evaluation of the gastric fundus, antrum, and duodenum. MATERIALS AND METHODS This study was performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12 swine, 6 had previously undergone bariatric embolization of the gastric fundus, and the 6 control swine had undergone a sham procedure with saline. Gross pathologic, histopathologic, and immunohistochemical examinations of the stomach and duodenum were performed. Specifically, mucosal integrity, fibrosis, ghrelin-expressing cells, and gastrin-expressing cells were assessed. RESULTS Gross and histopathologic evaluation of treatment animals showed healing or healed mucosal ulcers in 50% of animals, with gastritis in 100% of treatment animals and in five of six control animals. The ghrelin-immunoreactive mean cell density was significantly lower in the gastric fundus in the treated animals compared with control animals (15.3 vs 22.0, P < .01) but similar in the gastric antrum (9.3 vs 14.3, P = .08) and duodenum (8.5 vs 8.6, P = .89). The gastrin-expressing cell density was significantly lower in the antrum of treated animals compared with control animals (82.2 vs 126.4, P = .03). A trend toward increased fibrosis was suggested in the gastric fundus of treated animals compared with controls (P = .07). CONCLUSIONS Bariatric embolization resulted in a significant reduction in ghrelin-expressing cells in the gastric fundus without evidence of upregulation of ghrelin-expressing cells in the duodenum. Healing ulcerations in half of treated animals underscores the need for additional refinement of this procedure.

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients

OBJECTIVE 1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. STUDY DESIGN Retrospective cohort study. METHODS Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. RESULTS Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). CONCLUSION FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression.

Blast phase in chronic myelogenous leukemia is skewed toward unusual blast types in patients treated with tyrosine kinase inhibitors: A comparative study of 67 cases

OBJECTIVES To compare the features of the blast phase of chronic myelogenous leukemia (CML) in patients treated with tyrosine kinase inhibitors (TKIs) with those in the pre-TKI era. METHODS Sixty-seven patients with blast phase CML were identified in the Duke Pathology database from 1991 to 2011. The morphology and immunophenotype of blasts were evaluated, along with cytogenetic studies and associated findings in the peripheral blood and bone marrow. RESULTS In the TKI era, the blasts were more frequently of a type other than the usual myeloid or lymphoid types when compared with the pre-TKI era. Blast phase in TKI-treated patients was associated with a higher peripheral WBC count and a lower blast percentage in the bone marrow. Of the 23 patients with cytogenetic studies during blast phase, additional cytogenetic changes more frequently occurred in patients with an unusual blast type, and some patients showed these changes months before the onset of blast phase. CONCLUSIONS Blast phase CML in TKI- and non-TKI-treated patients differs in the morphology and immunophenotype of blasts, cytogenetic findings, and associated findings in the peripheral blood and bone marrow.