Chemotherapy and imatinib-induced molecular remission in lymphoid blast crisis after 20 years of "untreated" chronic myeloid leukemia.
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Adult↗
Biomedical subjects
Hakan Goker
Publications and source records attributed to Hakan Goker.
Unusual extramedullary recurrences and breast relapse despite hepatic GVHD after allografting in Ph+-ALL.
Extramedullary recurrences with or without bone marrow involvement are reported in up to a half of leukemic relapses after BMT. Our report describes a case of an extramedullary recurrence and breast relapse after second-allografting in a female patient with Ph+-acute lymphoblastic leukemia (ALL), occurring when there was active hepatic GHVD. This case illustrates the complex relationship between graft-versus-host disease (GVHD) and graft-versus-leukemia since she had no evidence of leukemia in her marrow demonstrating 100% full-donor chimerism while she had ALL relapse in her breast.
Breast↗
Changing clinical manifestations of a T-peripheral lymphoma: from hypereosinophilic syndrome to questionable Kimura's disease resulting in parotid mass.
The diagnosis of low-grade lymphoproliferative disorders during a long clinical course sometimes represents a great clinical challenge. The idiopathic hypereosinophilic syndrome (HES) represents a pre-malignant state in some patients and close follow-up is necessary to detect early signs of malignant transformation. Kimura's disease (KD) mimicking HES is an immune mediated inflammatory disorder that usually involves the head and neck region, primarily affecting the salivary glands, adjacent muscle and regional lymph nodes. Clinically, it is very difficult to differentiate KD from salivary gland lymphoid malignancies. Lymphomas may uncommonly present as a parotid mass. One, herein, would like to present a 35-year-old patient with changing clinical presentation patterns over a period of more than 6 years of follow-up. The first clinical presentation of the patient was HES. The 'diagnosis' of KD was reached after 4 years of management with HES. The final manifestation was parotid gland, preauricular and cutaneous manifestations of a peripheral T-cell lymphoma. This unique clinical presentation pattern of the patient may represent the distinct pathobiological progression of a clonal neoplastic lymphoproliferative disorder.
Adult↗
Over-expression of angiotensin-converting enzyme (CD 143) on leukemic blasts as a clue for the activated local bone marrow RAS in AML.
Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. There are preliminary data that local RAS might also be involved in leukemogenesis. ACE hyper-function may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow micro-environment, finally removing the anti-proliferative effect of AcSDKP on the hematopoietic cells and blasts. Renin expression could have a role on the leukemia development and angiotensin may act as an autocrine growth factor for acute myeloid leukemia (AML) cells. The aim of this study is to search ACE (CD 143) surface antigen by flow-cytometric analyses on the leukemic blast cells taken from the bone marrow of the patients with AML. Bone marrow aspiration materials and peripheral blood samples were obtained from 11 patients with AML (eight males, three females; aged 46 (range 26-67) years) and six patients with non-malignant hematological disorders (four males, two females; aged 56 (range 22-71) years). ACE (CD 143) surface antigen was shown to be over-expressed in leukemic myeloid blast cells. ACE is positively correlated with bone marrow blast count. Elucidation of the pathological activity of the local RAS-mediated regulation of the leukemogenesis is both pathobiologically and clinically important, since the angiotensin peptides represent a molecular target in the disease management.
Acute Disease↗
Unchanged global fibrinolytic capacity during the course of hematopoietic stem cell transplantation.
Hemostatic changes due to vascular endothelial damage are seen during the course of hematopoietic stem cell transplantation (HSCT). The fibrinolytic response to ongoing hemostatic activation in HSCT remains to be elucidated. Global fibrinolytic capacity (GFC) is a novel method, which reflects the amount of generated D-dimer when fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. The aim of this study was to serially assess GFC at certain critical time points (days -1, +7, +14, +21 prior to and following stem cell infusion) during the course of HSCT. The study group comprised 16 patients with hematological malignancies (11 women, five men; median age 32+/-9 years) in whom HSCT had been performed. Thirty healthy adults (21 women, nine men; median age 31+/-7 years) served as controls. In this study, global fibrinolytic response, as reflected by GFC, was unchanged despite ongoing hemostatic activation, as indicated by D-dimer, moreover GFC remained stable, despite the development of thrombocytopenia associated with HSCT prior to platelet engraftment. Our results indicate that a global fibrinolytic response was impaired as a compensatory response to endothelial activation and to other hemostatic changes seen in HSCT. Further studies in larger HSCT populations are warranted to better understand the implications of these findings.
Adult↗
Spontaneous splenic rupture in a healthy allogeneic donor of peripheral-blood stem cell following the administration of granulocyte colony-stimulating factor (g-csf). A case report and review of the literature.
Human granulocyte colony-stimulating factor (G-CSF) is a hematopoietic hormone promoting the growth, proliferation, differentiation and maturation of myeloid and leukocytic lineages. G-csfs have been used to improve granulocyte count in neutropenic patients, reduce the incidence and duration of neutropenia in patients receiving cytotoxic chemotherapy and to mobilize peripheral blood stem cells prior to leukapheresis for using in both autologous and allogeneic hematopoietic cell transplantation. In general, side-effects are mild to moderate and life threatening side-effects like splenic rupture are very rare. We herein, report a case of spontaneous splenic rupture secondary to high-dose G-CSF use (20 mcg/kg/day), in a healthy female allogeneic donor of peripheral-blood stem cell (PBSC) .
Abdominal Pain↗
Plasma osteopontin levels are elevated in non-ST-segment elevation acute coronary syndromes.
BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.
Aged↗
Local umbilical cord blood renin-angiotensin system.
Local bone marrow (BM) renin-angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34(+) hematopoietic stem cells (HSC). Angiotensin II stimulates the proliferation and differentiation of the HSC populations through the activation of AT1 receptors on HSC. Umbilical cord blood (UCB) is a rich source of HSC. The existence of a complete local UCB RAS has not been previously investigated. In this study, local synthesis of the major RAS components, namely, angiotensin-converting enzyme (ACE), renin, and angiotensinogen, was identified by demonstrating their corresponding mRNAs using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in human UCB. Local RAS could regulate cellular growth in a variety of tissues including the BM. Major RAS peptides can exert significant effects on primitive pluripotential HSC populations. Further studies should focus on the interactions between possible autocrine, paracrine, endocrine, and intracrine actions of the local UCB RAS and growth, engraftment, differentiation, and plasticity functions of HSC of UCB origin.
Angiotensin II↗
Unusual extramedullary relapses under imatinib mesylate treatment in chronic myeloid leukemia.
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Adult↗
Bone marrow and peripheral blood C-kit ligand concentrations in patients with thrombocytosis and thrombocytopenia.
C-kit ligand (stem cell factor, SCF) is a hematopoietic growth factor with diverse effects. It has stimulatory effects on megakaryocytopoiesis acting in synergism with interleukin-3 (IL-3), thrombopoietin (TPO) and granulocyte-macrophage colony stimulating factor (GM-CSF). The relationship between SCF and megakaryocytopoiesis, especially the correlations between blood and bone marrow SCF levels have been not clearly established in the literature. We therefore, investigated peripheral and bone marrow SCF levels in patients with thrombocytosis and thrombocytopenia. Subjects were divided into three groups: those with (i) thrombocytopenia, (ii) thrombocytosis and (iii) healthy adults as controls. When the three groups were compared, the mean peripheral blood SCF level of the thrombocytosis group (2149±197) was significantly higher than the thrombocytopenia (1586±178) and normal control groups (1371±68; p<0.05) and the bone marrow SCF level was higher (2694±267) than the thrombocytopenia group (1700±182; p<0.05). In the correlation analysis, considering all the groups together the bone marrow and peripheral blood SCF concentrations were positively and significantly correlated (p<0.01; r=0.93). Correlations between platelet number and both bone marrow SCF concentration (p<0.01; r=0.51) and peripheral blood concentrations (p<0.01; r=0.40) were also shown. Our results indicate that SCF is operative in the pathological megakaryopoiesis of clonal origin and reactive thrombocytosis both in the local bone marrow microenvironment and the peripheral circulating blood. We feel that further studies on the platelet-SCF relationship and SCF levels in different disease states are required.
Adult↗
Detection of inhibition of bovine viral diarrhea virus by aromatic cationic molecules.
Bovine viral diarrhea virus (BVDV) is an economically significant pathogen of cattle and a problematic contaminant in the laboratory. BVDV is often used as an in vitro model for hepatitis C virus during drug discovery efforts. Aromatic dicationic molecules have exhibited inhibitory activity against several RNA viruses. Thus, the purpose of this research was to develop and apply a method for screening the aromatic cationic compounds for in vitro cytotoxicity and activity against a noncytopathic strain of BVDV. The screening method evaluated the concentration of BVDV in medium and cell lysates after 72 h of cell culture in the presence of either a 25 or 5 microM concentration of the test compound. Five of 93 screened compounds were selected for further determination of inhibitory (90 and 50%) and cytotoxic (50 and 10%) concentration endpoints. The screening method identified compounds that exhibited inhibition of BVDV at nanomolar concentrations while exhibiting no cytotoxicity at 25 microM concentrations. The leading compounds require further investigation to determine their mechanism of action, in vivo activity, and specific activity against hepatitis C virus.
Animals↗
Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: preliminary evidences.
Until last the decade, the renin-angiotensin system (RAS) was considered as a circulating endocrine system. It is now known that there are local RASs in many tissues. It has also recently been hypothesized that there exists a local bone marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of this study was to detect BM and peripheral blood levels of the essential RAS components in normal and leukemic hematopoiesis. Concentrations of renin and angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and 10 post-treatment megaloblastic anemia patients with normal blood counts, as controls. In the leukemia group, the ACE concentration was found to be significantly higher in the BM (38+/-6.2 U/l) than in the peripheral blood (29.5+/-5.3 U/l), (p=0.029). In the leukemia group, although the BM renin concentration was higher than the peripheral blood levels (21.3+/-8.3 vs. 18.6+/-6.2 U/l), this difference was not statistically significant (p=0.196). In the control group, mean BM renin levels were insignificantly lower than in the peripheral blood (8.6+/-3 vs. 12.1+/-4.6 pg/ml) (p=0.059). In the leukemia group, serum ACE levels positively correlated with BM and peripheral blood blast percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral blast percentages (p<0.01) were inversely correlated with serum potassium in the leukemia group.The results of this study can be considered as the preliminary evidence supporting the hypothesis of the presence of a local BM RAS. Further, molecular biologic and immunohistochemical studies are needed to shed light on this important subject. A better understanding of the interrelationships of RAS and hematopoiesis will bring new insights into the pathobiology and even novel therapies for such neoplastic diseases.
Adolescent↗
Thrombopoietin as a drug: biologic expectations, clinical realities, and future directions.
After the cloning of thrombopoietin (c-mpl ligand, Tpo) in 1994, 2 recombinant thrombopoietic growth factors, full-length glycosylated recombinant human Tpo (reHuTPO) and polyethylene glycol conjugated megakaryocyte growth and development factor (PEG-reHuMGDF), have been studied in humans in a variety of clinical settings. Both thrombopoietins are generally well tolerated if administered intravenously (IV). The c-mpl ligands produce a dose-related enhancement of platelet levels, reduce nonmyeloablative chemotherapy-induced mild thrombocytopenia, and mobilize hematopoietic progenitors. On September 11, 1998, the development of PEG-reHuMGDF was suspended in the U.S., due to formation of the neutralizing anti-Tpo antibody. Those neutralizing antibodies lead to thrombocytopenia and pancytopenia in some patients receiving subcutaneous (SC) PEG-reHuMGDF. Japanese investigators indicate that the probability of antibody formation against PEG-reHuMGDF is low when the drug is administered IV instead of SC. reHuTPO has a more favorable safety profile from the point of antibody production. The c-mpl ligands can improve apheresis yields when administered to normal platelet donors. Preliminary data about the use of PEG-reHuMGDF in myelodysplasia, aplastic anemia, and immune thrombocytopenic purpura are promising. Tpo is usually not effective in myeloablative thrombocytopenia when bone marrow hematopoietic progenitors are not present. The major obstacle for the thrombopoietins is their delayed action for managing clinical thrombocytopenia. This review will focus on the biologic basis, current clinical experience, and future directions for the use of thrombopoietic molecules as drugs. The identification of a safe, effective, and potent pharmacologic platelet growth factor could significantly improve the management of thrombocytopenia-induced bleeding.
Animals↗
Current therapy for Behçet's disease.
Classified among the vasculitides, the clinical spectrum of Behçet's disease (BD) ranges from a mild mucocutaneous disease to a life-threatening systemic vasculitis, characterized by remissions and recurrences. The major morbidity is recurrent eye inflammation that may lead to blindness, but severe central nervous system, gastrointestinal, or vascular involvement may occur and might be fatal. In contradistinction to most other vasculitides, the venous system is commonly affected in BD. The treatment of BD is usually symptomatic and palliative. This includes topical steroids for orogenital ulcers, nonsteroidal antiinflammatory agents for joint involvement, and colchicine as prophylaxis against disease flares (although evidence that colchicine prevents recurrences of oral and genital ulcers is restricted to female patients). Immunosuppressives and cytotoxic agents are used for more severe involvement, and thalidomide and interferon have attracted attention in recent years.
Adrenal Cortex Hormones↗