NK-cell-associated receptor expression in hepatosplenic T-cell lymphoma, insights into pathogenesis.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
C A Hanson
Publications and source records attributed to C A Hanson.
WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature.
Explore the source record for details and available documents.
Adolescent↗
Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma.
Secondary myelodysplastic syndrome (sMDS) and acute myelogenous leukemia (AML) have been recognized with increasing frequency following autologous stem cell transplantation (ASCT). A retrospective analysis of 230 consecutive patients with Hodgkin's lymphoma (HL, 64) and non-Hodgkin's lymphoma (NHL, 166) who underwent ASCT was conducted to assess the incidence and risk factors for the development of sMDS/AML. At a median follow up of 41 months (range 0.1-177 months), 10 of 230 patients (4.3%) developed sMDS/AML. The 5-year-actuarial incidence of sMDS/AML was 13.1% and 5-year cumulative incidence by competing risk analysis was 4.2%. The median time to development of sMDS/AML was 39.9 months from the time of ASCT (range 12.1-62.0 months). Complex karyotypes at diagnosis of sMDS/AML included structural anomalies and/or loss of chromosome 5 (eight patients), 7 (five patients), 17 (two patients) and 20 (two patients). All patients subsequently died, at a median of 6.8 months (range 0-39.9) from diagnosis of sMDS/AML. Fluorescent in situ hybridization (FISH) analysis for -5/5q- and -7/7q- were normal in all six patients whose pre-ASCT bone marrow was available for testing. Five of the six had samples available for testing at diagnosis of sMDS/AML and all had abnormal FISH results. By univariate statistical analysis, male gender (P=0.01), prior alkylating agents (mechlorethamine for HL, P=0.001 and cyclophosphamide for NHL, P=0.05) and the number of prior treatment regimens (P=0.04) were significantly associated with the development of sMDS/AML. Given the relatively low incidence rate of sMDS/AML, these analyses are primarily exploratory in nature but provide some insight into relevant risk factors and illustrate the risk of developing sMDS/AML after myeloablative conditioning and ASCT for lymphoma.
Adult↗
B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules.
Initial work has shown that clonal B cells from B-chronic lymphocytic leukemia (B-CLL) are able to synthesize pro-angiogenic molecules. In this study, our goal was to study the spectrum of angiogenic factors and receptors expressed in the CLL B cell. We used ELISA assays to determine the levels of basic fibroblast growth factors (bFGF), vascular endothelial growth factor (VEGF), endostatin, interferon-alpha (IFN-alpha) and thrombospondin-1 (TSP-1) secreted into culture medium by purified CLL B cells. These data demonstrated that CLL B cells spontaneously secrete a variety of pro- and anti-angiogenic factors, including bFGF (23.9 pg/ml +/- 7.9; mean +/- s.e.m.), VEGF (12.5 pg/ml +/- 2.3) and TSP-1 (1.9 ng/ml +/- 0.3). Out of these three factors, CLL B cells consistently secreted bFGF and TSP-1, while VEGF was expressed in approximately two-thirds of CLL patients. Of interest, hypoxic conditions dramatically upregulated VEGF expression at both the mRNA and protein levels. We also employed ribonuclease protection assays to assay CLL B cell expression of a variety of other angiogenesis-related molecules. These analyses revealed that CLL B cells consistently express mRNA for VEGF receptor 1 (VEGFR1), thrombin receptor, endoglin, and angiopoietin. Further analysis of VEGFR expression by RT-PCR revealed that CLL B cells expressed both VEGFR1 mRNA and VEGFR2 mRNA. In summary, these data collectively indicate that CLL B cells express both pro- and anti-angiogenic molecules and several vascular factor receptors. Because of the co-expression of angiogenic molecules and receptors for some of these molecules, these data suggest that the biology of the leukemic cells may also be directly impacted by angiogenic factors as a result of autocrine pathways of stimulation.
Angiogenesis Inhibitors↗
Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome.
Ten anemic patients with favorable myelodysplastic syndrome (MDS) were first treated with two 5-week courses of amifostine alone (each course consisted of 200 mg/m(2) of the drug given intravenously three times a week for 3 weeks), followed by an additional two courses combined with subcutaneous erythropoietin (EPO) (150 U/kg, three times a week for 8 weeks). The study patients either had previously failed to respond to treatment with EPO or had pretreatment serum EPO levels of more than 100 mU/ml. None of the patients experienced a complete or partial response in anemia or other cytopenias. We conclude that amifostine alone or in combination with EPO has limited therapeutic activity in MDS.
Aged↗
Myelodysplasia with fibrosis: a distinct entity?
Explore the source record for details and available documents.
Bone Marrow↗
Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study.
This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.
Humans↗
Detection of diagnostically critical, often hidden, anomalies in complex karyotypes of haematological disorders using multicolour fluorescence in situ hybridization.
Multicolour fluorescence in situ hybridization (M-FISH) simultaneously detects all 24 human chromosomes in unique fluorescent colours. The identification of diagnostically critical gene rearrangement(s) in complex karyotypes of haematological disorders continues to be a challenge. We present five cases in which t(9;11), complex t(8;22), t(12;21) and t(11;14) were detected primarily using M-FISH and were confirmed using locus-specific probes. We conclude that M-FISH can be effective in complete characterization of critical gene rearrangements in haematological disorders.
Acute Disease↗
Cytogenetic findings and their clinical relevance in myelofibrosis with myeloid metaplasia.
The prognostic significance of bone marrow cytogenetic lesions in myelofibrosis with myeloid metaplasia (MMM) was investigated in a retrospective series of 165 patients. An abnormal karyotype was demonstrated in 57% of patients. At diagnosis (n = 92), 48% of the patients had detectable cytogenetic abnormalities, and clonal evolution was frequently demonstrated in sequential studies. More than 90% of the anomalies were represented by 20q-, 13q-, +8, +9, 12p-, and abnormalities of chromosomes 1 and 7. Of these, 20q-, 13q- and +8 were the most frequent sole abnormalities, each occurring in 15-25% of the abnormal cases. Trisomy 9 and abnormalities of chromosomes 1 and 7 were equally prevalent but were usually associated with additional cytogenetic lesions. Chromosome 5 abnormalities were infrequent but were over-represented in the group of patients exposed to genotoxic therapy. In a multivariate analysis that incorporated other clinical and laboratory variables, the presence of an abnormal karyotype did not carry an adverse prognosis. Instead, +8, 12p-, advanced age and anaemia were independent prognostic determinants of inferior survival. In particular, survival was not adversely affected by the presence of either 20q- or 13q-.
Adult↗
Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia.
Recent reports suggest that the expression of germline (GL) Ig variable region heavy-chain genes (VH) is a negative prognostic factor for B-cell chronic lymphocytic leukaemia (B-CLL) patients and that CLL B-cell CD38 expression may be a surrogate marker of Ig VH gene status. Currently, however, the usefulness of this surrogate marker is controversial. Therefore, our goal was to study the ability of CD38 to act as a surrogate marker for Ig VH somatic mutation (SM), and to identify differences in overall survival (OS), progression-free survival (PFS) and response in B-CLL patients based on these two markers. We first assessed the relationship between CD38 expression and Ig VH status on 131 B-CLL patients, including 66 patients enrolled in three North Central Cancer Treatment Group Trials. Although the mean percentages of CD38+ clonal B cells were significantly higher for patients classified as GL versus SM, CD38 was not a reliable marker for clonal B-cell SM. Overall, GL patients exhibited significantly shorter OS and PFS times than SM patients. Despite the inability of clonal B-cell CD38 expression to predict Ig VH mutation status, patients with < or =30% CD38+ cells did have shorter PFS and OS times than did CLL patients with < 30% CD38+ cells. Thus, the relationship between CD38 expression and Ig VH mutation status in B-CLL is not straightforward. Nevertheless, analysis in a co-operative group clinical trial setting suggests that both B-cell markers alone or in combination may have clinical usefulness. These data strongly encourage the study of these biological markers as they relate to disease heterogeneity in B-CLL.
ADP-ribosyl Cyclase↗
Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia.
BACKGROUND: Trazodone has been used widely to treat insomnia in depressed patients. When used in combination with electroconvulsive therapy (ECT), trazodone has been suspected to cause cardiovascular side effects. METHOD: A retrospective study was done of 100 patients who received ECT with concurrent trazodone. One patient was excluded because permission to review the patient's records had not been given. The remaining 99 patients were matched with control ECT patients. RESULTS: No statistically significant between-group differences were identified in cardiovascular side effects, although a trend toward more orthostatic hypotension was observed in patients taking trazodone. CONCLUSION: Administering low-dose trazodone for insomnia in conjunction with ECT does not appear to increase cardiovascular complications. The true incidence of adverse cardiac events was not higher than 3.66% at a 95% confidence level.
Adult↗
Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.
Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.
Adult↗
Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma.
Mantle-cell lymphoma (MCL) has a poorer prognosis than other small B-cell lymphomas, thus a definitive diagnosis is essential. The t(11;14)(q13;q32) associated with MCL juxtaposes portions of CCND1 (11q13) and IGH (14q32), resulting in over-expression of cyclin D1. In this study, a highly sensitive two-colour fluorescence in situ hybridization (FISH) method was developed to detect t(11;14)(q13;q32) in nuclei isolated from paraffin-embedded tissue. Twenty-three MCLs, 13 normal controls and nine small B-cell lymphomas other than MCL were studied by FISH. Each MCL had been previously investigated to detect genomic IGH-CCND1 fusion by polymerase chain reaction (PCR) using DNA extracted from frozen tissue. The IGH-CCND1 fusion detection rate in the MCLs was 96% by FISH compared with 35% by PCR. By FISH, one MCL and three small B-cell lymphomas other than MCL harboured abnormalities involving only IGH. Less than 1% of cells showed false-positive IGH-CCND1 fusion in normal specimens by FISH. Thus, this highly sensitive FISH assay is very useful in confirming the diagnosis of MCL, has wide applicability as it may be performed on both paraffin-embedded and fresh tissue, and may also facilitate detection of translocations involving these loci in tumours other than MCL.
Case-Control Studies↗
Motion analysis in two dimensions of radial-ulnar deviation of type I versus type II lunates.
The motions of 2 different types of lunate (type I, no medial hamate facet; type II, medial hamate facet) were evaluated and compared during radial-ulnar deviation of the wrist using radiography and magnetic resonance imaging. Ten right wrists (5 type I and 5 type II lunates) were studied using posteroanterior and lateral x-rays. Six of the 10 normal volunteers (3 type I and 3 type II lunates) were studied using magnetic resonance imaging in 6 positions of radial-ulnar deviation. In the radiographic study the ulnar shift ratio of the lunate (USR), the shortest distance between the proximal ulnar tip of the lunate and the distal ulnar edge of the sigmoid notch of the radius (R-L), the closest distance between the distal ulnar tip of the lunate and the proximal pole of the hamate (L-H), the radius of curvature of the proximal head of the capitate (Cr) on posteroanterior view, and the radiolunate angle on lateral view were measured in each wrist in each of the 6 positions. There were statistically significant differences between type I and II lunates with regard to average maximum ulnar deviation of USR and R-L, total change of USR, R-L distance and L-H distance, average L-H distance and Cr distance in all positions, and average radiolunate angle in neutral and 15 degrees ulnar deviation. In the magnetic resonance imaging study the wrists with a type I lunate did not have contact between the lunate and hamate in any position; the wrists with a type II lunate did have contact between the hamate and the lunate, but only in ulnar deviation. The results of this study demonstrate that the kinematics of a type I lunate are different from those of a type II lunate during radial-ulnar deviation of the wrist.
Adult↗
The (11;14)(q13;q32) translocation in multiple myeloma. A morphologic and immunohistochemical study.
We identified 24 cases of multiple myeloma with the t(11;14)(q13;q32). In 22 cases, the t(11;14)(q13;q32) was part of a complex karyotype, and in 2 cases it was an isolated abnormality. All patients had clinical and laboratory features consistent with multiple myeloma. The median degree of plasma cell involvement in the bone marrow was 60%, and in 10 cases, the plasma cells had a lymphoplasmacytoid appearance. Of the 24 cases, 21 had intermediate or high proliferative rates based on labeling index studies. Immunohistochemical studies performed on all bone marrow biopsy specimens showed strong cyclin D1 nuclear positivity in 19 cases. There also was strong cyclin D1 nuclear positivity found in 6 of 30 additional cases without the t(11;14)(q13;q32) demonstrated by routine cytogenetics. The t(11;14)(q13;q32) in multiple myeloma results in overexpression of the cyclin D1 protein, which can be demonstrated by immunohistochemical stain. The cyclin D1 stain results in the additional cases of multiple myeloma suggest that the t(11;14)(q13;q32) may be more common than previously thought and may be missed by routine cytogenetics, particularly if the proliferative rate is low.
Adult↗
Immunophenotypic analysis of peripheral blood and bone marrow in the staging of B-cell malignant lymphoma.
This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.
Adult↗
Isolated isochromosome 17q: a distinct type of mixed myeloproliferative disorder/myelodysplastic syndrome with an aggressive clinical course.
A clinicopathologic study was performed on 15 patients with haematological malignancies in which isochromosome 17q [i(17q)] was the sole structural chromosome abnormality identified in bone marrow. The data indicated that an isolated i(17q) is associated with a distinct type of mixed chronic myeloproliferative/myelodysplastic disorder with an aggressive clinical course. The patients ranged in age from 37 to 83 years (median 60) with a M:F ratio of 3:1. All cases were chronic myeloid disorders with mixed proliferative and dysplastic features, making classification difficult. 11 patients tested for BCR/ABL gene fusion were normal. A low bone marrow blast count (<5%) at presentation was a typical finding. All cases had severe myeloid dysplasia which included non-segmented neutrophils and an increase in the monocyte/macrophage lineage. Fluorescence in situ hybridization (FISH) analysis of one case showed the i(17q) to involve all myeloid lineages, but not the lymphocytes. For cases with complete follow-up (n = 11) the median survival was 2.5 years (range 0.83-5.25) and 64% progressed to AML prior to death. The following features were identified which defined the haematological disorder associated with an isolated i(17q): (1) adult patient, (2) chronic myeloid disorder with clonal involvement of all myeloid lineages, (3) mixed chronic myeloproliferative/myelodysplastic features, (4) severe hyposegmentation of neutrophil nuclei, (5) prominence of the monocyte/macrophage lineage, (6) high risk for progression to AML, and (7) median survival of 2.5 years.
Adult↗
Idiopathic thrombocytopenic purpura associated with breast cancer: a case report and review of the current literature.
The association of solid tumors with idiopathic thrombocytopenic purpura (ITP) is rare. Before this study, there have been three case reports indicating an association between breast cancer and ITP. We present a 69-year-old man with metastatic breast cancer and progressive thrombocytopenia without any evidence of a leukoerythroblastic picture or etiologies for the thrombocytopenia. Serum platelet antibodies were identified. A bone marrow biopsy showed small foci of metastatic breast cancer, thrombocytopenia, and normal number of megakaryocytes. A subsequent trial of steroids resulted in a marked improvement of the patient's thrombocytopenia. This is the fourth case report indicating an association of breast cancer and ITP.
Aged↗