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S T Traweek

Publications and source records attributed to S T Traweek.

At least 19 recordsLinked to original sources

Post transplant CD8+ gammadelta T-cell lymphoma associated with human herpes virus-6 infection.

Gammadelta T-cell lymphoma is a rare T-cell lymphoproliferative disorder that has been reported in both immunocompetent and immunocompromised persons. This report describes a forty eight year old patient who developed gammadelta T-cell lymphoma four years after undergoing living-related kidney transplantation. The lymphoma expressed CD2, CD3, CD7, CD8 and CD56, and the gammadelta T-cell receptor and did not express CD5, CD4 and the alphabeta T-cell receptor. In addition, HHV-6 was cultured from the patient's bone marrow, marking the first time that this virus has been associated with gammadelta T-cell lymphoma. Since all patients with gammadelta T-cell lymphoma described to date have responded poorly to standard combination chemotherapies, the patient was treated with the purine analogue 2-chlorodeoxyadenosine. While he responded transiently to treatment, long term remission was not achieved indicating that additional therapeutic approches still need to be developed, for the management of this disorder.

Antigens, CD↗

Primary central nervous system lymphomas: a 30-year experience at a single institution.

Primary central nervous system lymphoma (PCNSL) is a rare disease that has been increasing in frequency. Clinical, histologic, and immunohistochemical data from 64 cases of PCNSL seen at Duke University Medical Center since 1968 were reviewed and tumors were classified using the REAL classification system. Thirty-two patients were male and 32 were female, with a mean age of 57.1 years, ranging from 16 to 82 years. Large B-cell lymphoma represented overwhelming the majority of PCNSL, accounting for 81% of all cases. Phenotypic T-cell lymphomas were rare with only two cases over the course of the study. Epstein-Barr virus was detected only in the immunocompromised patients and was identified in 75% of those immunocompromised patients who were tested. Overall survival was poor with a mean survival of 357 days and median survival of 158 days. One- and three-year survival rates were 29.6% and 7.8%, respectively. Type of treatment, duration of symptoms, site of lesion, and histologic subtype were not significant prognostic indicators, whereas concurrent immunosuppression was the strongest predictor of poor outcome. In AIDS patients (which accounted for 21.9% of the study group), the median survival was 65 days, which was significantly different than that seen in the immunocompetent group of 217 days (P = .001).

Adolescent↗

Predictive value of intraoperative biopsies and liver function tests for preservation injury in orthotopic liver transplantation.

Eighty liver allografts were studied to determine the predictive value of intraoperative biopsies and postoperative liver function tests for the development of preservation injury (PI). Peak transaminase (aspartate transaminase [AST] and alanine transaminase [ALT]) and prothrombin time (PT) values achieved by each patient during postoperative days (POD) 1 through 7 were determined. PI in day 0 preperfusion biopsies (0Pre) (obtained immediately before implantation) and postperfusion biopsies (0Post) (obtained immediately after revascularization) was categorized by histological criteria as present or absent. PI in biopsies taken during POD 2 through 14 was histologically graded as either moderate-to-severe, mild, or absent. Of the 80 allografts, 8 were omitted because of primary nonfunction or postoperative complications. 0Pre and 0Post biopsies were available on 25 of 72 (35%) and 69 of 72 (96%) allografts, respectively. Only 2 (8%) of the 0Pre biopsies showed histological PI compared with 48 (70%) of the 0Post biopsies. Fifty-nine patients were biopsied between POD 2 through 14. Of these, 15, 28, and 16 patients developed moderate-to-severe, mild, or no evidence of PI, respectively. The presence of PI in the 0Post biopsy strongly correlated with the development of PI during POD 2 through 14 (P < .0005). Peak AST and ALT values in patients with moderate-to-severe PI on POD 2 through 14 were significantly elevated compared with those patients with either mild (P = .01 and .03) or no PI (P = .02 and .006). Because of extensive overlap in AST and ALT values between the three groups, however, transaminase values were not useful in predicting the presence or absence of PI in the individual case. The development of PI during POD 2 through 14 correlated with advanced donor age (P = .06) but was unassociated with 0Pre biopsy findings, cold ischemia time, or peak PT values. We conclude that the 0Post biopsy is a valuable tool for the prediction of subsequent PI in the early postoperative period. In contrast, 0Pre biopsy findings and peak AST and ALT values are not useful in the assessment of PI.

Adolescent↗

Neural cell adhesion molecule (CD56)-positive acute myelogenous leukemia and myelodysplastic and myeloproliferative syndromes.

The CD56 antigen is normally expressed on natural-killer cells but has additionally been shown to be present on a variety of hematologic malignancies, including a subset of acute myelogenous leukemia (AML). There is disagreement, however, about its prognostic significance and its association with specific cytogenetic abnormalities. All clinical samples from June 1994, through September 1995, with increased myeloblasts were analyzed by multiparameter flow cytometry for anomalous expression of CD56. Patients with CD56+ blast cells were selected, and morphologic review was performed. Clinical information was obtained, and cytogenetic data were reviewed. Southern blot analysis to detect rearrangement of the mixed lineage leukemia (MLL) gene was performed when possible. The samples from 23 of 114 patients studied demonstrated anomalous expression of CD56 on myeloblasts, including patients with AML, myelodysplastic syndromes (MDS), and chronic myelogenous leukemia in blast crisis. The samples from 10 of 15 patients with CD56+ AML demonstrated at least partial monocytic differentiation. Dysplastic features were displayed in the samples of 12 patients. Correlation with specific cytogenetic abnormalities was not found. The MLL gene was rearranged in five of 18 patients. Seventeen patients have died, with a median survival of 4.6 months for patients with AML. Three have sustained a complete remission. One has findings of high-grade myelodysplastic syndrome. Two were unavailable for follow-up. Expression of CD56 was found in 20% of patients with increased myeloblasts, including patients with high-grade MDS, chronic myelogenous leukemia in blast crisis, and AML. This phenotype was associated with dysplasia, monocytic differentiation, and rearrangement of the MLL gene.

Adolescent↗

Myelodysplastic syndrome occurring after autologous bone marrow transplantation for lymphoma. Morphologic features.

Clonal karyotypic abnormalities characteristic of myelodysplastic syndrome (MDS) occur in up to 18% of patients who undergo autologous bone marrow transplantation (auto-BMT) for the treatment of lymphoma. Morphologic changes are often subtle and may not meet the French-American-British Cooperative Group criteria for MDS. We retrospectively assessed dysplastic changes in peripheral blood and bone marrow specimens obtained before and after transplantation from nine patients and correlated them with karyotype and survival. All patients had normal cytogenetic study results before transplantation and had clonal karyotypic abnormalities develop after auto-BMT. Four patients (with aggressive MDS) survived a short time and died of acute myelogenous leukemia or MDS-related complications, four (with indolent MDS) had a prolonged survival period, and one patient died of recurrent lymphoma. The group with aggressive MDS had significantly more bone marrow trilineage dysplasia before auto-BMT than did the group with indolent MDS or cytogenetically normal auto-BMT controls, suggesting that stem cell damage occurred before transplantation and was not detected by pretransplantation cytogenetic analysis. Comparatively greater dyserythropoiesis and dysmegakaryopoiesis were present after transplantation; these changes were similar to those seen in de novo MDS. Posttransplantation dysplasia in the group with indolent MDS was analogous to the atypia related to the transplantation process.

Adult↗

Craniocerebral plasmacytoma: MR features.

We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with gray matter on T2-weighted MR images, and diffusely enhanced after administration of contrast material, bearing some similarities to meningioma. A diagnosis of solitary craniocerebral plasmacytoma should be considered when a mass with these imaging features is seen, because total excision may not be necessary for this radiosensitive tumor.

Adult↗

Myelodysplasia and acute myeloid leukemia occurring after autologous bone marrow transplantation for lymphoma.

Secondary hematopoietic disease manifesting as acute myeloid leukemia, myelodysplastic syndrome or clonal karyotypic abnormalities, has been recently recognized as a relatively frequent and potentially serious complication of autologous bone marrow transplantation for both Hodgkin's disease and non-Hodgkin's lymphoma. The available evidence suggests the disease results primarily from repeated exposure of the host stem cells to therapeutic agents before the time of transplant, but a conspiratory role for the transplantation procedure itself cannot be entirely excluded. Strategies to decrease the incidence of secondary hematopoietic disease include earlier stem cell harvest and/or transplantation, and the performance of screening karyotypic studies on the bone marrow prior to autologous grafting.

Acute Disease↗

Detection of Kaposi's sarcoma-associated herpesvirus-like DNA sequence in angiosarcoma.

The partial DNA sequence of a putative new herpesvirus has recently been isolated from almost all cases of Kaposi's sarcoma (KS), from a small subset of AIDS-related lymphomas, and from a high proportion of multicentric Castleman's disease. The presence of this KS-associated herpesvirus, which is also known as human herpes virus 8 (KSHV/ HHV8), has not been reported in vascular tumors other than KS. We therefore examined a series of vascular neoplasms of both endothelial and pericyte derivation using polymerase chain reaction to detect a 233-hp segment of the viral DNA. KSHV/HHV8 sequences were found in 7 of 24 (29%) angiosarcomas and 1 of 20 (5%) hemangiomas but not in any hemangiopericytomas (0 of 6). The presence of the virus in angiosarcoma was confirmed by direct sequencing of the polymerase chain reaction product and Southern blotting in one case each. Only one of the affected patients was known to be immunocompromised. By detecting its presence in a significant proportion of angiosarcomas, this study extends the number of tumors associated with KSHV/HHV8, further tightens its association with malignancy, and suggests a tropism of the virus for endothelial cells. The presence of KSHV/HHV8 in angiosarcomas in addition to classical KS also indicates that immunosuppression is not a requisite for viral infection.

Adolescent↗

Detection of myeloperoxidase gene expression in minimally differentiated acute myelogenous leukemia (AML-M0) using in situ hybridization.

Acute leukemias containing > 3% myeloperoxidase (MPO)-positive blast cells, as detected cytochemically, are considered to be myelogenous in origin, regardless of the immunophenotypic markers expressed. Conversely, acute leukemias that express only myeloid antigens are also considered to be acute myelogenous leukemia (AML), even in the absence of MPO. These MPO-negative AMLs, designated AML-M0 in the FAB classification, currently require either immunophenotypic or electron microscopic studies for identification. To examine the association of MPO and myeloid antigen expression in AML, particularly at the early stages of myeloid cell differentiation, we have used in situ hybridization (ISH) to evaluate MPO gene expression in myeloid leukemia cell lines and a variety of well-characterized acute leukemias, including six cases of AML-M0. Strong positivity for MPO mRNA was detected in the myeloid leukemia cell line HL-60 and in 22 of 27 AMLs (three AML-M0, four AML-M1, eight AML-M2, five AML-M4, two AML-M5a). No MPO gene expression was detected in three AML-M0, one AML-M5a, one AML-M7, 5 acute lymphoblastic leukemia, the lymphoid cell lines Molt-4 and Namalwa, or in the early myeloid cell lines KG-1 and KG-1a. Ultrastructural studies for MPO activity were performed on four AML-M0; one leukemia showed both gene expression and cytochemical activity, whereas two others contained neither MPO transcripts nor enzyme. Weak MPO gene expression was evident in one AML-M0 that was negative for enzymatic activity by electron microscopy. These studies show MPO gene expression can be detected by ISH in about half of AML-M0, supporting their presumed myelocytic derivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Trisomy 11: an association with stem/progenitor cell immunophenotype.

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis.

Acute Disease↗

Expression of interleukin-1 receptor antagonist protein in malignant lymphomas. An immunohistochemical study.

OBJECTIVE: Interleukin-1 (IL-1) receptor antagonist (IL-1ra) is a naturally occurring modulator of IL-1 that functions by competitively binding to IL-1 receptors without producing biologic effects. Interleukin-1 is believed to be a mediator involved in production of constitutional symptoms in patients with malignant lymphoma. Because we know of no study regarding IL-1ra expression in lymphomas, we tried to demonstrate the presence of IL-1ra in lymphomas using immunohistochemistry. DESIGN: Anti-IL-1ra monoclonal antibody was applied to paraffin sections of Hodgkin's disease and non-Hodgkin's lymphoma (NHL) with avidin-biotin complex method. RESULTS: Interleukin-1 receptor antagonist was found to be present primarily in benign reactive histiocytes in neoplastic tissue. Positivity for IL-1ra was found in 12 (67%) of 18 cases of Hodgkin's disease and 53 (29%) of 184 cases of NHL. The positivity rate varied in different subtypes of NHL. Three percent (1 in 30) of follicular small cleaved-cell lymphomas contained IL-1ra-expressing histiocytes, whereas 52% (17 of 33) of diffuse mixed-cell and 27% (12 of 44) of diffuse large-cell lymphomas contained IL-1ra-positive histiocytes. Nine of 13 (69%) cases of high-grade NHLs contained IL-1ra-expressing histiocytes. Among cases of NHL, the higher-grade NHL cases showed higher percentages of positivity. CONCLUSIONS: The findings further support the hypothesis that IL-1 may play a role in producing constitutional symptoms.

Humans↗

Clonal karyotypic hematopoietic cell abnormalities occurring after autologous bone marrow transplantation for Hodgkin's disease and non-Hodgkin's lymphoma.

Over a 6-year period, 275 patients were treated with autologous bone marrow transplantation (auto-BMT) for advanced-stage malignant lymphoma. After BMT, clonal chromosomal abnormalities were detected in hematopoietic cells from 10 patients. All 10 had morphologically and cytogenetically normal BMs at the time of stem cell harvest. The cytogenetic changes were first detected 1.8 to 6.5 years (mean, 3.9) after induction chemotherapy, and 0.5 to 3.1 years (mean, 1.4) after transplantation, and were characteristic of those reported for therapy-related myelodysplastic syndrome (MDS) in 9 of the patients: abnormalities of chromosome 5 or 7 (classical-form) were present in 4, 11q23 or 21q22 abnormalities (topoisomerase II-related form) were detected in 3, and a combination of both forms was seen in 2 patients. Clonal 2p abnormalities were found in the 1 remaining patient. The abnormal karyotypes were associated with morphologically recognizable MDS in 3 patients and with acute myeloid leukemia (AML) arising in MDS in 2. Four of these patients have died: 3 of AML and 1 of infection. One patient is still alive with cytopenia. The clonal cytogenetic abnormalities were not associated with MDS in 5 patients: 1 has died of recurrent lymphoma, 2 have cytopenia, and 2 still have no morphologic or clinical evidence of MDS after short follow-up (4 and 13 months). Compared with a control group matched for disease, length of follow-up, and treatment with auto-BMT, there were no statistically significant associations between the development of clonal chromosomal abnormalities and age, number of chemotherapeutic regimens, prior local radiation, BMT conditioning regimen (with or without total body irradiation), or type of lymphoma. These studies show that the risk of developing clonal cytogenetic changes after auto-BMT for malignant lymphoma is approximately 9% at 3 years, even when pre-BMT karyotypic studies are normal. The exact significance of these cytogenetic abnormalities in the absence of MDS or AML is unclear.

Adult↗

Localization of amplified MYC gene sequences to double minute chromosomes in acute myelogenous leukemia.

Cytogenetic and molecular studies were performed on two dmin-bearing acute myelogenous leukemia (FAB-M2) samples. Both cases were characterized by complex karyotypes containing interstitial deletions of the long arm of chromosome 8 altering band 8q24.1, aberrations affecting the short arm of chromosome 17, and multiple double minute chromosomes (dmin). Using a 1.4 kb cDNA probe coding for the third exon of the MYC oncogene, DNA slot blots indicated MYC gene sequences were amplified in both samples. Fluorescence in situ hybridization using a 9.0 kb genomic probe for MYC was performed in one case and localized the amplified MYC gene sequences to the dmin. Neither patient achieved a complete remission using traditional induction chemotherapy. The complex karyology with amplification of MYC gene sequences appears to represent a poor prognostic subgroup of acute myelogenous leukemia.

Aged↗

Detection of the Philadelphia chromosome in paraffin-embedded tissue by fluorescence in situ hybridization.

The bcr-abl fusion gene situated on the Philadelphia chromosome is a tumor-specific marker for chronic myelogenous leukemia. We evaluated the usefulness of two color fluorescence in situ hybridization with bcr and abl probes as a means of detecting the Philadelphia chromosome in formalin-fixed, paraffin-embedded sections of spleen and lymph node specimens from eight patients with myeloproliferative diseases showing clinical and morphological features of chronic myelogenous leukemia in accelerated phase. Our analysis showed co-localized hybridization signals corresponding to the bcr-abl fusion product in tissue sections from six patients previously found to have the Philadelphia chromosome by conventional cytogenetics and polymerase chain reaction. The two remaining specimens lacked bcr-abl fusion signals and were obtained from patients who were negative for the Philadelphia chromosome by cytogenetic and polymerase chain reaction analysis. We conclude that fluorescence in situ hybridization is a sensitive method for the detection of the bcr-abl fusion gene in histological specimens from patients with chronic myelogenous leukemia. The technique may become a useful tool in the evaluation of tissue specimens from patients with chronic myelogenous leukemia and related Philadelphia chromosome-positive hematologic malignancies.

Fusion Proteins, bcr-abl↗

Detection of trisomy 8 by fluorescence in situ hybridization on bone marrow smears from patients with subtle myelodysplastic changes.

Trisomy 8 is the most common hyperdiploid numerical chromosomal abnormality that is found in myelodysplastic syndromes (MDSs). We explored the utility of combining fluorescence in situ hybridization interphase cytogenetics with routine morphologic analysis to characterize cases for which signs and symptoms were suggestive of MDS in which dysplastic changes were insufficient for a definitive diagnosis. Hybridization with a chromosome 8-specific centromeric probe was performed on bone marrow smears that were obtained from four patients with cytogenetically documented trisomy 8 and hematopoietic cell atypia that was suggestive but not diagnostic of MDS. Signals that corresponded to trisomy 8 were detected in 14.6% to 32.2% of the cells (detection threshold of trisomic clone, 5.0%). The conditions of two patients have remained hematologically stable with no disease progression, and these two patients are now considered to have refractory anemia. The conditions of the other two patients rapidly progressed to morphologically recognizable MDSs. This study demonstrates that the detection of trisomy 8 by fluorescence in situ hybridization can provide useful supplemental information in bone marrow specimens with morphologic changes that are suggestive of but not sufficient for a diagnosis of MDS. It should prove to be useful when standard cytogenetic analysis has not been performed or when it is not readily available.

Adult↗

Prognostic significance of immunohistochemical analysis of cathepsin D in low-stage breast cancer.

BACKGROUND: Cathepsin D is an estrogen-regulated lysosomal protease that may be overexpressed in breast cancer. Several studies based on biochemical analysis of tumor cytosol have shown that high levels of cathepsin D are associated with poor outcome in patients with breast cancer. In contrast, a few immunohistochemical studies have shown that cathepsin D positivity in breast cancer cells indicates a favorable prognostic outcome or is of no prognostic significance. METHODS: Because of the current controversy, the authors studied, using immunohistochemistry, the distribution (0 to 3) and intensity (0 to 3) of cathepsin D in Stage I and II infiltrating ductal carcinoma of the breast from 245 patients treated at the City of Hope National Medical Center, Duarte, California, from 1970 to 1986. A commercially available rabbit antiserum to purified human cathepsin D and the standard avidin-biotin complex method were used. Statistical analysis was based on a combined low (0 or 2) or high (3 to 6) score. RESULTS: A high cathepsin D score was associated with Stage II disease (P = 0.007), positive lymph nodes (P = 0.019), high nuclear grade (P = 0.005), and c-erbB-2 oncogene amplification (P = 0.013). Cathepsin D positivity was not an independent prognostic indicator of disease-free survival (DFS) or overall survival (OS). In a subgroup analysis, the presence of cathepsin D had only a modest association with predicting a shorter DFS in patients with negative lymph nodes (P = 0.072) or positive progesterone receptors (PR) (P = 0.086). CONCLUSIONS: Immunohistochemical analysis of cathepsin D, with the antiserum used in this study, is not an independent predictor of outcome in patients with breast cancer because of its strong associations with several well-established prognostic indicators.

Adult↗

High-grade transformation of chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma. Genotypic confirmation of clonal identity.

The abrupt appearance of a high-grade tumor in patients with low-grade malignant lymphoma usually is associated with an accelerated clinical disease course. The high-grade lymphoma may take a variety of histologic forms and often, but not always, represents evolution of the original low-grade disease, as shown by immunophenotypic or immunogenotypic studies. The authors describe the transformation of a variety of low-grade B-cell neoplasms to high-grade tumors in four patients. The initial diagnoses included chronic lymphocytic leukemia and mantle cell lymphoma in one patient each and low-grade follicular lymphoma in two patients. The high-grade tumors were classified as lymphoblastic lymphoma in one patient and small noncleaved cell lymphoma in two patients. The high-grade component manifests primarily in the peripheral blood as circulating blast-like cells consistent with large-cell lymphoma in the remaining patient. In each case, immunophenotypic studies showed identical monoclonal surface immunoglobulin expression on the low- and high-grade tumors. Immunoglobulin heavy chain gene and kappa light chain gene studies showed identical clonally rearranged bands in paired samples from three of the four patients, a finding indicative of clonal identity. Unexpectedly, dissimilar immunoglobulin light and heavy chain gene rearrangements were detected in the paired samples from one patient with previously diagnosed follicular lymphoma, making the relationship of the two tumors from this patient uncertain; however, additional Southern blot analysis of the bcl-2 gene showed identical rearrangements in both lesions. Furthermore, polymerase chain reaction across the t(14;18) major breakpoint region in both tumors amplified nucleotide fragments of identical size, confirming the clonal identity of the low- and high-grade lymphomas despite the divergent immunoglobulin gene studies. These studies show that low-grade malignant lymphomas of small lymphocytic, mantle cell, or follicular small cleaved cell types may assume high-grade morphologic characteristics, that this change is the result of transformation of the preexisting low-grade malignant neoplasm, and that this progression, like typical Richter's syndrome, is associated with a dramatically accelerated clinical course. In addition, these studies confirm previous reports that disparate immunoglobulin light and heavy chain gene rearrangements are not necessarily an indicator of different cellular origins, and additional genotypic studies occasionally may be required to show the clonal identity of the cell population involved in these morphologic transformations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗