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David Myerson

Publications and source records attributed to David Myerson.

15 recordsLinked to original sources
PubMed2006

Minimal disease detection and confirmation in hematologic malignancies: combining cell sorting with clonality profiling.

BACKGROUND: In this study we demonstrate the technical application of flow cytometry and cell sorting combined with gene-rearrangement clonality profiling to detect and confirm minimal disease in 2 leukemia and 2 lymphoma cases. METHODS: Specimens with low percentages (0.05%-5%) of abnormal lymphoid populations were identified by flow cytometry. The abnormal lymphoid populations were sorted by flow cytometry, and the purified tumor populations along with unsorted fractions were subsequently analyzed for the presence of clonal gene rearrangements by PCR and fluorescence-based capillary electrophoresis fragment analysis. RESULTS: In 3 cases, distinct clonality profiles could be detected in the purified tumor cell fraction, and suspicious amplicons of identical sizes were detected among the polyclonal backgrounds in the unsorted specimens. For 1 patient, a monoclonal signal was detected in the sorted tumor cell fraction but not in the unseparated bone marrow specimen containing 0.05% abnormal lymphoblasts. A subsequent bone marrow specimen containing 4.8% recurring leukemia cells tested positive with a clonality profile that matched the previous profile in the sorted cell population. CONCLUSIONS: The described method integrating 2 technologies allows genotypic confirmation of an aberrant population detected by immunophenotype to increase diagnostic certainty. This strategy provides a sensitive tool for disease monitoring without the need for patient-specific primer design and assay optimization required for quantitative PCR analysis.

Adult↗
PubMed2006

Reduced incidence of acute and chronic graft-versus-host disease with the addition of thymoglobulin to a targeted busulfan/cyclophosphamide regimen.

To reduce the incidence of graft-versus-host disease (GVHD), we added Thymoglobulin (THY) to dose-adjusted oral busulfan plus cyclophosphamide (targeted BUCY). The starting dose of THY was 4.5 mg/kg given over days -3, -2, and -1, escalated in steps of 1.5 mg/kg in cohorts of 15 evaluable patients. Escalation was dependent on acute GVHD incidence and Epstein-Barr virus reactivation. Fifty-six patients with myelodysplastic syndrome and other myeloid disorders underwent transplantation with peripheral blood progenitor cells from related (n=30) or unrelated (n=26) donors. All but 2 patients achieved engraftment, and 56% survived in remission beyond 1 year. The incidence of acute GVHD was 50%, and that of chronic GVHD was 34%. The highest THY dose was 6.0 mg/kg, a dose at which 1 patient experienced Epstein-Barr virus reactivation. Nine patients did not receive the prescribed THY dose. Results were comparable for related and unrelated transplants and for patients given 4.5 or 6.0 mg/kg THY. Among 27 myelodysplastic syndrome patients (14 with related and 13 with unrelated donors) who underwent transplantation concurrently with targeted BUCY without THY, the incidence of acute and chronic GVHD was 82%. Thus, THY 4.5 to 6.0 mg/kg seemed beneficial for GVHD prevention in BUCY-conditioned patients who underwent transplantation with peripheral blood progenitor cells, although relapse-free survival did not differ significantly from that in comparable historical controls not given THY.

Acute Disease↗
PubMed2005

Molecular identification of an invasive gingival bacterial community.

A woman with neutropenia developed gingival hyperplasia. Biopsy showed invasion of gingival tissue with mats of filamentous organisms, and molecular analysis by polymerase chain reaction and fluorescence in situ hybridization revealed Capnocytophaga sputigena, Leptotrichia species, and Fusobacterium nucleatum. Oral bacterial flora may cause invasive gingival disease with hyperplasia in immunocompromised patients.

Capnocytophaga↗
PubMed2005

BK DNA viral load in plasma: evidence for an association with hemorrhagic cystitis in allogeneic hematopoietic cell transplant recipients.

We performed a case-control study to determine the association of BK plasma viremia with hemorrhagic cystitis (HC) in hematopoietic cell transplant (HCT) recipients. Thirty cases of HC (14 of which occurred after platelet engraftment with documented BK viruria [BK-HC]) were compared with matched controls. Weekly plasma samples were tested for BK virus DNA by polymerase chain reaction (PCR). BK viremia detected before or during the disease was independently associated with HC (adjusted odds ratio = 30, P < .001); BK viremia was even important before clinical symptoms of HC occurred (odds ratio = 11, P < .001). Cases of HC and BK-HC had a significantly higher peak of BK plasma viral load than controls. BK virus was detected by in situ hybridization in bladder biopsies of 2 cases with severe HC and long-lasting BK viremia. BK virus seems to play a role in the development of HC and quantitative detection of BK DNA in plasma appears to be a marker of BK virus disease in HCT recipients.

Adolescent↗
PubMed2005

Contribution of bone marrow-derived endothelial cells to human tumor vasculature.

It has been shown that bone marrow-derived stem cells can form a major fraction of the tumor endothelium in mouse tumors. To determine the role of such cells in human tumor angiogenesis, we studied six individuals who developed cancers after bone marrow transplantation with donor cells derived from individuals of the opposite sex. By performing fluorescence in situ hybridization (FISH) with sex chromosome-specific probes in conjunction with fluorescent antibody staining, we found that such stem cells indeed contributed to tumor endothelium, but at low levels, averaging only 4.9% of the total. These results illustrate substantial differences between human tumors and many mouse models with respect to angiogenesis and have important implications for the translation of experimental antiangiogenic therapies to the clinic.

Bone Marrow Cells↗
PubMed2005

Specific delineation of BK polyomavirus in kidney tissue with a digoxigenin-labeled DNA probe.

The detection of BK polyomavirus (BK virus, BKV) in kidney tissue is hampered by nonspecificity of antibodies suited to immunohistochemistry, and nonspecific background with in situ hybridization. The biotin-labeled DNA probe that is commercially available (Enzo Life Sciences, Inc.) shows good signal, but the intrinsic background in kidney tissue is high. We determined that the intrinsic background is due to endogenous biotin or biotin-binding activity in the renal tubular epithelium. Neither antibody blocking procedures nor an avidin/biotin block were entirely satisfactory for eliminating this background staining. We developed a digoxigenin-labeled DNA probe, and protocol, for detecting BK virus in formalin-fixed, paraffin embedded, kidney tissue obtained at autopsy. The hybridization signal is strong and there is no perceptible background staining. Eleven negative control kidneys all failed to hybridize. Conditions for low stringency hybridization may be employed, detecting both the related JC polyomavirus and BKV. Alternatively, high stringency hybridization conditions may be utilized, detecting BKV only. BK associated tubular necrosis is clearly demonstrated in two cases of BK nephritis.

Autopsy↗
PubMed2005

Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia.

We evaluated the outcomes of allogeneic hematopoietic cell transplantation (HCT) in 43 patients with chronic myelomonocytic leukemia. Patients were classified according to the French-American-British and World Health Organization classifications, as well as the International Prognostic Scoring System and the M.D. Anderson prognostic score. Comorbidity scores were assessed by using an HCT-specific comorbidity index. Patients were aged 1 to 66 years (median, 48 years). Twenty-one patients received transplants from related donors (18 HLA-identical siblings and 3 HLA-nonidentical family members), and 22 received transplants from unrelated donors (18 HLA matched and 4 HLA nonidentical). Several busulfan or total body irradiation-based conditioning regimens were used. Sustained engraftment was achieved in 41 patients. Eighteen are alive at 1.9 to 14.1 years, for an estimated relapse-free survival of 41% at 4 years. Ten patients have relapsed, thus leading to a cumulative incidence of 23% at 4 years. Risk category by International Prognostic Scoring System, World Health Organization, M.D. Anderson prognostic score, or proliferative/dysplastic status had no statistically significant association with outcomes. However, patients with higher comorbidity scores had worse overall survival than patients with lower scores (P = .01). There was a trend for a higher relapse incidence among patients at higher risk by the M.D. Anderson prognostic score. The data suggest that patients with few or no comorbidities and those who undergo transplantation earlier in the disease course have the highest probability of successful outcome after allogeneic HCT.

Adolescent↗
PubMed2005

Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial.

BACKGROUND: Soy isoflavones have numerous biological properties that suggest that they may protect against colorectal cancer. Colorectal epithelial cell proliferation has been used extensively as an intermediate endpoint biomarker for colorectal neoplasia. OBJECTIVE: We tested the hypothesis that supplementation with soy protein containing isoflavones decreases colorectal epithelial cell proliferation. DESIGN: A 12-mo randomized intervention was conducted in men and women aged 50-80 y with recently diagnosed adenomatous polyps. One hundred fifty participants were enrolled and randomly assigned to an active treatment group (58 g protein powder/d containing 83 mg isoflavones/d; +ISO) or a control group (ethanol-extracted soy-protein powder containing 3 mg isoflavones; -ISO). Biopsy specimens from the cecum, sigmoid colon, and rectum were collected at baseline and at the 12-mo follow-up. Ki-67 antibody immunohistostaining was used to detect cell proliferation. One hundred twenty-five participants completed the study, and proliferation was measured in the first 91 who completed the study. RESULTS: In the sigmoid colon, cell proliferation increased by 0.9 (95% CI: 0.09, 1.9) labeled nuclei per crypt more (11%) in the +ISO group than in the -ISO group over the 12-mo intervention, which was opposite the direction predicted. The number of labeled nuclei per 100 mum crypt height also increased more in the +ISO than in the -ISO group. In the cecum and sigmoid colon, but not in the rectum, the proliferation count increased as the serum genistein concentration increased. Proliferation distribution and crypt height were not changed by treatment at any site. CONCLUSIONS: Supplementation with soy protein containing isoflavones does not reduce colorectal epithelial cell proliferation or the average height of proliferating cells in the cecum, sigmoid colon, and rectum and increases cell proliferation measures in the sigmoid colon.

Adenomatous Polyps↗
PubMed2004

Influenza A pneumonia presenting as progressive focal infiltrates in a stem cell transplant recipient.

BACKGROUND: Stem cell transplant recipients are susceptible to pulmonary infections, including influenza A. Typically, isolated influenza pneumonia has a diffuse, interstitial infiltrate pattern. OBJECTIVES: To describe the unusual clinical and radiographic course of influenza A pneumonia in a stem cell transplant recipient. STUDY DESIGN: Case report in which microbiologic assays, bronchoscopic and pathologic specimens are obtained. RESULTS: We describe a patient with influenza A pneumonia 8 months following a peripheral blood stem cell transplant who presented with minimal respiratory symptoms and rapidly progressing, focal pulmonary infiltrates. The large size and appearance of the masses have not been reported before in a patient with isolated influenza. CONCLUSION: This case highlights the differences of presentation and importance of early diagnosis and treatment of immunocompromised patients infected with influenza.

Adult↗
PubMed2003

Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation.

Marrow cells of myeloid lineage from 115 patients with myelodysplastic syndrome (MDS) were characterized by multidimensional flow cytometry and compared with findings in 104 patients with various disorders and 25 healthy donors. Based on phenotypic and scatter characteristics, a flow cytometric scoring system (FCSS) was developed that allowed for a simple numerical display of results. The flow cytometric scores were categorized as normal/mild (0-1), moderate (2-3), or severe (> or = 4). Most flow cytometric abnormalities were significantly (P <.05) more frequent in patients with MDS than in the control cohort. Flow cytometric scores in MDS patients were then retrospectively compared with marrow blast counts assessed by morphology, cytogenetics, hematologic parameters, and International Prognostic Scoring System (IPSS) risk categorization. The flow cytometric scores correlated inversely with leukocyte and absolute neutrophil counts (P <.01) and correlated directly with IPSS scores (P <.01) and with IPSS cytogenetic risk categories (P <.01). In 111 MDS patients who underwent allogeneic hematopoietic stem cell transplantation, flow scores correlated with posttransplantation outcome. The probabilities of posttransplantation relapse were 3%, 15%, and 33% for patients with mild, moderate, and severe FCSS scores, respectively (P <.01), and overall survival was 74%, 40%, and 36%, respectively, for the 3 groups (P <.01). In multivariate analyses, there was a significant contribution of the flow score independent of the IPSS in predicting survival and relapse (P <.01, P =.02, and P =.03, respectively). These data suggest that FCSS is useful in assessing marrows for diagnosis of MDS and in determining the prognostic outcome in patients with this disorder.

Antigens, CD↗
PubMed2002

Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity.

Ganciclovir effectively prevents cytomegalovirus (CMV) disease in the first 100 days after allogeneic hematopoietic stem cell transplantation (HSCT), but late-onset CMV disease is increasingly observed. We designed a prospective cohort study to define the incidence and risk factors for late CMV infection in patients who undergo HSCT. CMV-seropositive patients were studied prospectively for CMV infection (quantitative pp65 antigenemia, quantitative CMV-DNA, blood culture), T-cell immunity (CMV-specific CD4(+) T-helper and CD8(+) cytotoxic T-lymphocyte responses, CD4 and CD8 T-cell count, absolute lymphocyte count), and other transplantation-related factors. Univariate and multivariable analyses were used to assess the risk for late CMV infection and disease and to assess overall survival. Late CMV disease developed in 26 of 146 (17.8%) patients a median of 169 days after transplantation (range, 96-784 days); the mortality rate was 46%. Thirty-eight percent of patients surviving late disease had a second episode a median of 79 days after the first episode. At 3 months after transplantation, preceding detection of CMV pp65 antigenemia, CD4 T-cell counts lower than 50 cells/mm(3), postengraftment absolute lymphopenia levels lower than 100 lymphocytes/mm(3), undetectable CMV-specific T-cell responses, and graft-versus-host disease (GVHD) were associated with late CMV disease or death. After 3 months, continued detection of pp65 antigenemia or CMV DNA in plasma or peripheral blood leukocytes and lymphopenia (fewer than 300 lymphocytes/mm(3)) were strong predictors of late CMV disease and death. In conclusion, CMV viral load, lymphopenia, and CMV-specific T-cell immunodeficiency are predictors of late CMV disease and death after allogeneic stem cell transplantation. Prevention strategies should be targeted at patients in whom CMV reactivated during the first 3 months and those with poor CMV-specific immunity or low CD4 counts.

Cytomegalovirus↗
PubMed2002

Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts.

Human myocardium has long been considered to have essentially no intrinsic regenerative capacity. Recent studies in rodent models, however, have suggested the presence of an extracardiac stem cell population, perhaps in bone marrow, that is capable of some reconstitution of cardiomyocytes after injury. To determine whether similar mechanisms exist in the human heart, we evaluated human female allograft hearts transplanted into male patients. The presence of Y chromosomes in cardiomyocytes would indicate these cells arose from the recipient, rather than the donor heart. We identified 5 male patients who had retained a female heart at least 9 months before death and necropsy. Remarkably, in each case, the transplanted heart contained a minute but readily detectable fraction of Y chromosome-positive cardiomyocytes. The mean percentage of cardiomyocytes arising from the host was estimated to be 0.04% with a median of 0.016%. Most Y-positive cardiomyocytes were associated with regions of acute rejection, suggesting such chimerism involves an injury event. Furthermore, the sole patient whose immediate cause of death was allograft rejection showed a much higher percentage of host-derived cardiomyocytes, up to 29% in local, 1-mm(2) "hot spots." Thus, adult humans have extracardiac progenitor cells capable of migrating to and repopulating damaged myocardium, but this process occurs at very low levels.

Cell Differentiation↗
PubMed2002

Curative therapy of advanced essential thrombocythemia or polycythemia vera by hemopoietic stem cell transplantation.

Twenty-five patients with advanced essential thrombocythemia (ET; n = 13) or polycythemia vera (PV; n = 12) received hemopoietic stem cell transplants (HSCT) at the Fred Hutchinson Cancer Research Center. In most cases the indication to perform an HSCT was myelofibrosis with splenomegaly and peripheral blood cytopenias or the development of a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients were 18-60 (median 43) years old with intervals from diagnosis to HSCT of 8-348 (median 168) months. All but five patients had been treated with cytotoxic agents, and nine patients were splenectomized before transplant. Conditioning was performed with chemotherapy only or chemotherapy plus total body irradiation regimens followed by the infusion of either marrow (n = 19) or peripheral blood stem cells (n = 6) from related (n = 16) or unrelated (n = 9) donors. All evaluable patients showed sustained neutrophil engraftment. Nine patients (seven with AML/MDS, two with myelofibrosis) died of transplant-related complications, and 16 are surviving, 14 of them in continuous unmaintained remission. With a median follow-up of 41 (range 5-116) months after transplant, survival at 3 years is 64%. These data provide evidence that HSCT can be a curative treatment for patients with advanced PV and ET.

Adolescent↗
PubMedDate not supplied

The pathogenesis of villitis of unknown etiology: analysis with a new conjoint immunohistochemistry-in situ hybridization procedure to identify specific maternal and fetal cells.

The conjoint immunohistochemistry-in situ hybridization (IHC-ISH) procedure permits, under routine light microscopic conditions, simultaneous documentation of either a male or female karyotype plus the immunological phenotype of individual cells within paraffin-embedded tissues. We have used this technique to characterize the inflammatory response in placental villitis of unknown etiology (VUE). A male placenta with severe VUE and appropriate control placentas were analyzed. In situ hybridization probes concurrently label both the X and Y chromosomes. On the same tissue section, individual cells were characterized with antibodies to CD3, CD68, or CD20. The amnion and syncytiotrophoblast were delineated by cytokeratin antibody (AE1/AE3). A complete karyotyping was performed on amnion cells to validate the procedure. Amnion cell karyotyping confirmed the accuracy of the procedure. The VUE case revealed that 88.8% of intravillous CD3+ lymphocytes were female (maternal), while 11.2% were male (fetal). Intervillous CD3+ lymphocytes and CD68+ macrophages were universally female. Intravillous CD68+ cells were only 10.5% female. Perivillous CD68+ cells were 94.6% female. Remarkably, multinucleated giant cells were exclusively maternal. This study confirms that lymphocytes in VUE are predominately but not exclusively maternal T cells. Our findings indicate that invasion of fetal villi by maternal T cells is associated with focal destruction of the syncytiotrophoblast, clarifying how placental immuno-defensive mechanisms may be contravened.

Adult↗