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1.
Bratisl Lek Listy ; 117(2): 112-8, 2016.
Article in English | MEDLINE | ID: mdl-26830043

ABSTRACT

UNLABELLED: Career psychologists have argued that the career choice and personality interfere with each other. There have been lots of investigations aimed at seeking the relationships between career interests and personality characteristics. There is limited knowledge on personality profiles of the anatomists and on how they are related with their specialty choices. AIM: In this research we aimed to explore the relationship between personality and career interests of anatomists. METHOD: Out of 279 anatomists who had been asked to complete the survey via e-mail including three questionnaires, 79 (53 male, 26 female) responded in the present study. Personality was assessed using the Cloninger's Temperament and Character Inventory (TCI). The career interest was determined by Holland's Theme Codes. RESULTS: The order of high frequency Holland's Codes was as follows: social (44.3%), realistic (35.4%), investigative (27.8%), conventional (19.0%), artistic (7.6%), and enterprising (5.1%). With regard to temperament components of TCI was as follows: novelty seeking (mean=17.7±4.7), harm avoidance (mean=13.9±6.1), reward dependence (mean=13.2±3.4), and persistence (mean=5.4±2.1). Character profiles are as follows: self-directedness (mean=33.1±6.3), self-transcendence (mean=17.9±7.6), and cooperativeness (mean=30.6±5.9). According to the last questionnaire, the most important cause for choosing anatomy is the interest in anatomy since medical study time. CONCLUSION: These results in part support Holland's theory, which takes the career as a function of personality and the personality profiles of anatomists have affected the motivation to select their specialty choice partially (Tab. 3, Fig. 1, Ref. 10).


Subject(s)
Anatomists/psychology , Career Choice , Personality Inventory , Adult , Character , Female , Humans , Male , Middle Aged , Self-Assessment , Surveys and Questionnaires , Temperament
2.
Int J Psychiatry Med ; 45(2): 97-109, 2013.
Article in English | MEDLINE | ID: mdl-23977815

ABSTRACT

OBJECTIVE: Acute myocardial infarction (MI) has significant and detrimental effects on the lifestyles of the patients. It has been shown that quality of life (QoL) in patients with MI is impaired in every aspect. This study aims to evaluate the impact of depression and physical comorbidity on QoL in Turkish patients with acute first MI. METHOD: This multi-center cross-sectional study was carried out in 15 centers with 998 patients hospitalized for acute first MI. For detection of depression, Beck Depression Inventory (BDI) was used. For evaluation of QoL, World Health Organization Quality of Life Questionnaire (WHOQOL) was applied. RESULTS: The mean age of the patients was 57.5 +/- 10.1 years and 79.2 % (n = 792) of the patients were men. Patients with comorbid depression (BDI > or = 10) and comorbid medical conditions, and female patients had significantly lower scores in every domain of WHOQOL. In the regression analysis model, female gender, low education, comorbid medical conditions, especially comorbid hypertension, and BDI score were found to have a significant effect on the domains of WHOQOL. CONCLUSIONS: Female patients are more prone to impairment in quality of life after myocardial infarction. Both comorbid medical conditions and depression have a significant impact on the impairment of QoL in Turkish patients with acute MI. In order to improve the subjective wellbeing of post MI patients, both psychiatric and physical comorbidities must be detected and managed even in the short-term.


Subject(s)
Chronic Disease/psychology , Depressive Disorder/psychology , Myocardial Infarction/psychology , Quality of Life/psychology , Surveys and Questionnaires , Adult , Aged , Comorbidity , Cross-Sectional Studies , Depressive Disorder/diagnosis , Female , Humans , Interview, Psychological , Male , Middle Aged , Personality Inventory/statistics & numerical data , Psychometrics , Turkey
3.
Mediators Inflamm ; 2007: 65704, 2007.
Article in English | MEDLINE | ID: mdl-17497035

ABSTRACT

AIM: Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD). Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in OCD patients. METHODS: Plasma concentrations of TNF-alpha and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-alpha and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Both TNF-alpha and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P < .000, P < .001, resp.). In addition, the age of onset was negatively correlated with TNF-alpha level (r = -.402, P = .025) and duration of illness was weakly correlated with IL-6 levels (r: .357; P: .048) in patients group. CONCLUSION: OCD patients showed increases in TNF-alpha and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflammatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD.


Subject(s)
Interleukin-6/blood , Obsessive-Compulsive Disorder/blood , Tumor Necrosis Factor-alpha/blood , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male
4.
Int J Biol Markers ; 21(4): 206-10, 2006.
Article in English | MEDLINE | ID: mdl-17177157

ABSTRACT

BACKGROUND: Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascular endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND METHODS: Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were having the same malignancy, stage, metastatic site, performance status and age (+/-5 years) as patients in the VT group. RESULTS: Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). CONCLUSION: There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.


Subject(s)
Factor VIII/analysis , Neoplasms/mortality , Vascular Endothelial Growth Factor A/blood , Venous Thrombosis/blood , Adult , Aged , Fibrin Fibrinogen Degradation Products/analysis , Humans , Middle Aged , Neoplasms/blood , Prospective Studies
5.
Int J Biol Markers ; 21(4): 206-210, 2006.
Article in English | MEDLINE | ID: mdl-28207147

ABSTRACT

BACKGROUND: Venous thromboembolism (VT) increases mortality and morbidity in cancer patients. The primary aim of this study was to evaluate the effect of VT on the survival of cancer patients and its relationship with serum vascu-lar endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND METHODS: Eighty-two patients with locally advanced or metastatic cancer were included in this study between September 2001 and March 2004, and 31 of them had VT. Fifty-one matched-paired cancer patients without VT were prospectively selected as a control group in the same period. Criteria for the selection of control group patients were hav-ing the same malignancy, stage, metastatic site, performance status and age (5 years) as patients in the VT group. RESULTS: Plasma factor VIII and serum D-dimer levels in the VT group were significantly higher than those in the control group (p=0.030 and p=0.016, respectively). However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT group, the median survival of patients who had higher serum VEGF levels (>150 pg/mL) was significantly shorter than that of patients in the same group with lower serum VEGF levels (p=0.005). The median survival of the VT group was 14 months, whereas it was 25 months in the control group (p=0.199). CONCLUSION: There was a worse prognostic trend for cancer patients with VT. Nevertheless, the difference in survival was not statistically significant between the groups. Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer patients with VT. Cancer patients with VT and higher serum VEGF levels had a significantly poorer prognosis.

6.
Med Oncol ; 19(1): 59-67, 2002.
Article in English | MEDLINE | ID: mdl-12025892

ABSTRACT

All-trans retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia. Because ATRA has effects (increase in apoptosis, suppression of bcl-2), it has also been used for the treatment of other French-American-British (FAB) subtypes of acute myelogenous leukemia (AML). To find out the in vivo and in vitro effects of ATRA in AML, we analyzed 37 patients with de novo AML. Twenty-seven patients received ATRA before remission-induction (RI) treatment (ATRA group). Results were compared to a control group (10 patients) that received induction without ATRA during the same time period. Bone marrow or peripheral blood samples were collected from all patients on d 0 and 4. The immunphenotype, myeloperoxidase (MPO), reac tion and the efflux uptake of rhodamine 123 (Rh123) were analyzed on myeloblasts in these samples. In the myeloblasts from patients treated with ATRA, the uptake of Rh123 was increased significantly (p = 0.026) from d 0 to d 4, and all other parameters remained unaltered. ATRA administration increased the complete remission (CR) rate (88%, 22/25 vs 55%, 5/9) significantly (p = 0.042). Logistic regression analysis revealed that ATRA administration was the important factor in CR, among other potential factors including age, white blood count, bcl-2 expression, and the uptake and efflux of Rh123 (p = 0.05). Estimated disease-free survival and overall survival were similar between these two groups (43% vs 37.5% and 51.2% vs 37.5%, respectively). In conclusion, ATRA treatment prior to RI treatment may improve the CR rate in patients with de novo AML, which seems to be related to its beneficial effect on multidrug resistance.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Cytarabine/therapeutic use , Leukemia, Myeloid/drug therapy , Rhodamine 123/metabolism , Tretinoin/therapeutic use , Acute Disease , Adolescent , Adult , Aged , Antigens, CD/metabolism , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biomarkers, Tumor/metabolism , Case-Control Studies , Cytarabine/administration & dosage , Drug Resistance, Multiple , Etoposide/administration & dosage , Female , Fluorescent Dyes/metabolism , Humans , Idarubicin/administration & dosage , Immunophenotyping , Leukemia, Myeloid/metabolism , Leukocyte Count , Male , Middle Aged , Proto-Oncogene Proteins c-bcl-2/metabolism , Remission Induction , Treatment Outcome
7.
Br J Haematol ; 116(2): 468-74, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11841454

ABSTRACT

To date, no randomized study has compared different doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF) following submyeloablative mobilization chemotherapy. Therefore, we evaluated the effect of different doses of rhG-CSF following mobilization chemotherapy on yields of CD34+ peripheral blood stem cells (PBSC). Fifty patients were randomized to receive 8 (n = 25) versus 16 microg/kg/d (n = 25) of rhG-CSF following mobilization chemotherapy. The median number of CD34+ cells collected after 8 microg/kg/d of rhG-CSF was 2.36 x 10(6)/kg (range, 0.21-7.80), compared with 7.99 (2.76-14.89) after 16 microg/kg/d (P < 0.001). Twenty out of 25 (80%) patients in the low-dose and 23 out of 25 (92%) in the high-dose rhG-CSF arm underwent high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Median days to white blood cell engraftment in patients mobilized with 8 microg/kg and 16 microg/kg of rhG-CSF were 12 (10-20) and 9 (8-11) respectively (P < 0.001). There was no difference between the two groups regarding the other parameters of peritransplant morbidity: days to platelet engraftment (P = 0.10), number of red blood cell (P = 0.56) and platelet transfusions (P = 0.22), days of total parenteral nutrition requirement (P = 0.84), fever (P = 0.93) and antibiotics (P = 0.77), and number of different antibiotics used (P = 0.58). These data showed that higher doses of rhG-CSF following submyeloablative mobilization chemotherapy were associated with a clear dose-response effect based on the collected cell yields. Based on the parameters of peritransplant morbidity, 8 microg/kg/d was as effective as 16 microg/kg/d except for a rapid neutrophil engraftment in the high-dose arm. Therefore, in routine clinical practice, despite some advantage in the use of higher doses of rhG-CSF, lower doses may be used for PBSC collections following chemotherapy-based mobilization regimens in this cost-conscious era.


Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Adolescent , Adult , Antigens, CD34 , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Cell Count , Drug Administration Schedule , Female , Hematopoietic Stem Cell Transplantation , Humans , Lymphoma/drug therapy , Lymphoma/therapy , Male , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/therapy , Recombinant Proteins , Stem Cells/immunology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/therapy , Time Factors
8.
J Clin Apher ; 16(2): 67-73, 2001.
Article in English | MEDLINE | ID: mdl-11746531

ABSTRACT

The objective of this study was to quantify subpopulations of CD34+ cells such as CD41+ and CD42+ cells that might represent megakaryocyte (MK) precursors in peripheral blood stem cell (PBSC) collections of normal, recombinant human granulocyte-colony stimulating factor (rhG-CSF) primed donors and to determine whether there is a statistical association between the dose infused megakaryocytic precursors and the time course of the platelet recovery following an allogeneic PBSC transplantation. Twenty-six patients with various hematologic malignancies transplanted from their HLA identical siblings between July 1997 and December 1999 were used. All patients except one with severe aplastic anemia who had cyclophosphamide (CY) alone received busulfan-CY as preparative regimen and cyclosporine-methotrexate for GVHD prophylaxis. Normal healthy donors were given rhG-CSF 10 microg/kg/day subcutaneously twice daily and PBSCs were collected on days 5 and 6. The median number of infused CD34+, CD41+ and CD42+ cells were 6.61 x 10(6)/kg (range 1.47-21.41), 54.85 x 10(4)/kg (5.38-204.19), and 49.86 x 10(4)/kg (6.82-430.10), respectively. Median days of ANC 0.5 x 10(9)/L and platelet 20 x 10(9)/L were 11.5 (range 9-15) and 13 (8-33), respectively. In this study, the number of CD41+ and CD42+ cells infused much better correlated than the number of CD34+ cells infused with the time to platelet recovery of 20 x 10(9)/L in 26 patients receiving an allogeneic match sibling PBSC transplantation (r = -0.727 and P < 0.001 for CD41+ cells, r = -0.806 and P < 0.001 for CD42+ cells, r = -0.336 and P > 0.05 for CD34+ cells). There was an inverse correlation between the number of infused CD41+ and CD42+ cells and duration of platelet engraftment. Therefore, as the number of CD41+ and CD42+ cells increased, duration of platelet engraftment (time to reach platelet count of > or = 20 x 10(9)/L) shortened significantly. Based on this data we may conclude that flow cytometric measurement of CD41+ and CD42+ progenitor cells may provide an accurate indication of platelet reconstitutive capacity of the allogeneic PBSC transplant.


Subject(s)
Graft Survival , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Platelet Glycoprotein GPIIb-IIIa Complex/analysis , Platelet Glycoprotein GPIb-IX Complex/analysis , Adolescent , Adult , Anemia, Aplastic/blood , Anemia, Aplastic/therapy , Biomarkers , Blood Platelets/chemistry , Blood Platelets/cytology , Female , Flow Cytometry , Hematologic Neoplasms/blood , Hematopoietic Stem Cell Mobilization , Histocompatibility , Humans , Male , Middle Aged , Nuclear Family , Platelet Count , Predictive Value of Tests , Transplantation Conditioning , Transplantation, Homologous
9.
Transfus Apher Sci ; 24(1): 23-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11515607

ABSTRACT

The effect of granulocyte colony-stimulating factor (G-CSF) on peripheral blood lymphocytes (PBL) and CD34+ cell frequency in the apheresis product has been determined in 25 healthy stem cell donors. Peripheral blood mononuclear cells (PBMNC) were collected after five days of G-CSF 10 microg/kg/day s.c., which was well tolerated. The median number of leukocytes increased eight-fold over that of pretreatment levels. Collection of PBMNC lasted a median of two (range, 1-3) days. The mean mononuclear cell (MNC) count and total lymphocyte percentage were 6.69 x 10(8)/kg and 59.08%, respectively, and the frequency of CD34+ cell expression was 2.1% in the apheresis product. The frequency of CD3+, CD4+, CD25+, NK and CD122+ cell expressions in mobilized PBMNC and PBL showed no significant difference. However, the frequency of CD8+, CD8+28+, CD3+DR+, CD19+, CD20+ and CD22+ B cells expression in the apheresis product increased significantly compared to steady-state PBL. In contrast, the frequency of the CD11 a+ and CD8+38+ cell expressions in the apheresis product was decreased compared to the steady-state PBL. The mean yield of CD34+ and CD3+ cells were 13.6 x 10(6) and 2.69 x 10(8)/kg of recipient body weight (RBW), respectively. Following allograft all patients engrafted with >0.5 x 10(9)/l neutrophil and < or = 20 x 10(9)/l platelets on a median of day 13 and 12, respectively. Nine patients had grade II-IV acute GVHD and chronic GVHD occurred in eight patients. Four patients died due to transplant-related complications. There was one late engraftment failure which occurred on the fifth month. Thirteen patients are still alive. In conclusion, these results indicate that administration of G-CSF at 10 microg/kg/day in normal donors alters the lymphocyte subsets and there are significant differences in the lymphocyte contents of the recipients before apheresis and in apheresis product.


Subject(s)
Antigens, CD34/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Transplantation/methods , Lymphocyte Subsets/drug effects , Adolescent , Adult , Antigens, CD34/analysis , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/toxicity , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunophenotyping , Leukapheresis/methods , Leukapheresis/standards , Male , Middle Aged , Transplantation, Isogeneic/adverse effects , Transplantation, Isogeneic/methods , Transplantation, Isogeneic/mortality
10.
Leukemia ; 15(8): 1268-73, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11480570

ABSTRACT

In order to investigate the frequency of HHV-8 in MM patients from another geographic location, we obtained fresh bone marrow (BM) biopsies from Turkish patients with MM (n = 21), monoclonal gammopathy of undetermined significance (MGUS) (n = 2), plasmacytoma (n = 1) with BM plasma cell infiltration, various hematological disorders (n = 6), and five healthy Turkish controls. The frequency of HHV-8 was analyzed by polymerase chain reaction (PCR) in two independent laboratories in the USA and in Turkey. Using fresh BM biopsies, 17/21 MM patients were positive for HHV-8 whereas all five healthy controls, and six patients with other hematological disorders were negative. Two patients with MGUS, and one patient with a solitary plasmacytoma were also negative. The data from the two laboratories were completely concordant. Also using primer pairs for v IRF and v IL-8R confirmed the results observed with the KS330233 primers. Furthermore, sequence analysis demonstrated a C3 strain pattern in the ORF26 region which was also found in MM patients from the US. Thus, HHV-8 is present in the majority of Turkish MM patients, and the absence of the virus in healthy controls further supports its role in the pathogenesis of MM.


Subject(s)
Bone Marrow/pathology , Bone Marrow/virology , Herpesviridae Infections/virology , Herpesvirus 8, Human/isolation & purification , Multiple Myeloma/virology , Biopsy , Herpesviridae Infections/epidemiology , Humans , Multiple Myeloma/epidemiology , Multiple Myeloma/etiology , Multiple Myeloma/pathology , Turkey/epidemiology
11.
Bone Marrow Transplant ; 27(5): 499-505, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11313683

ABSTRACT

We studied the effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic peripheral blood stem cell (PBSC) transplantation. Fifty-six patients with hematological malignancies who underwent allogeneic PBSC transplantation between 1995 and 1998 were entered into this study. Twenty-eight patients who received daily G-CSF from day +1 after allogeneic PBSC transplantation until the absolute neutrophil count (ANC) reached >0.5 x 10(9)/l for 3 consecutive days were compared with 28 patients (control group) who did not receive G-CSF in a non-randomized manner. The study group and the control group were comparable with respect to baseline patient and transplantation characteristics. Median times to ANC of >0.5 x 10(9)/l and 1 x 10(9)/l with or without G-CSF were 12 days (range 8-21), 13 days (10-32) (P = 0.04) and 13 days (9-21), 15 days (11-44) (P = 0.02), respectively. Median times to reach a platelet count of >20 x 10(9)/l with and without G-CSF were 11 days (0-20) and 13 days (9-26), respectively (P = 0.03). The incidence of febrile episodes was significantly lower with G-CSF, 75% vs 100% (P = 0.008). Patients receiving G-CSF had less grade III-IV mucositis than those who did not receive G-CSF (P = 0.01). There was also no increase in the incidence and severity of acute GVHD in patients using G-CSF (P = 0.22). Although the number of relapsing patients was greater in the G-CSF group (seven vs three patients), this was not statistically significant (P = 0.24). Disease-free and overall survival rates did not differ between the two groups (P = 0.58 and 0.53, respectively). The administration of G-CSF after allogeneic PBSC transplantation provided faster neutrophil and platelet engraftment associated with less severe mucositis and less febrile episodes.


Subject(s)
Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoiesis/drug effects , Hematopoietic Stem Cell Transplantation/methods , Adolescent , Adult , Case-Control Studies , Female , Graft vs Host Disease , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/standards , Histocompatibility , Humans , Infections , Male , Middle Aged , Nuclear Family , Recombinant Proteins , Recurrence , Survival Rate , Transplantation, Homologous/methods , Treatment Outcome
12.
Ther Apher ; 5(1): 54-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11258612

ABSTRACT

Allogeneic peripheral blood stem cell transplantation (PBSCT) is rarely applied for the treatment of severe aplastic anemia (SAA) because of questionable durability of engraftment and increased risk of graft versus host disease (GVHD). We performed allogeneic PBSCT in 3 SAA patients from their human leukocyte antigen (HLA)-identical siblings. One received bone marrow after conditioning with cyclophoshamide (Cy) plus antithymocyte globulin. He had a second transplant with peripheral blood stem cells from the original donor because of a graft failure (GF). Two other patients received PBSCT as a first option, with Cy as the only conditioning drug. The 3 patients received short-term methotrexate and cyclosporine as a postgrafting immunosupression. In the latter 2 cases, no GF has been observed, and a successful and complete hematological recovery was achieved and maintained for 28 and 25 months, respectively. In conclusion, PBSCT provides a quick and complete hematological recovery in SAA patients.


Subject(s)
Anemia, Aplastic/therapy , Stem Cell Transplantation , Adolescent , Adult , Fatal Outcome , Graft vs Host Disease/etiology , Humans , Leukapheresis , Male , Transplantation, Homologous
13.
Cytotherapy ; 3(4): 253-60, 2001.
Article in English | MEDLINE | ID: mdl-12171713

ABSTRACT

BACKGROUND: The effect of allogeneic hematopoietic cell transplantation (alloHCT) on hematologic malignancies is based on the graft-versus-malignancy effect. Obtaining this effect with reduced toxicity has been possible by non-myeloablative (NMA) alloHCT. Once mixed chimeric status, and host versus graft with graft versus host tolerance are achieved, further strengthening of chimerism and graft-versus-malignancy effect can be obtained by donor lymphocyte infusions (DLIs) when needed. METHODS: The patient group consisted of 13 patients with advanced hematological malignancies: seven had CML, four of them in blastic-, two in chronic- and the remainder in accelerated-phase; four patients with AML, refractory or in second remission state; one patient with primary refractory secondary AML; and one patient with ALL relapsed after alloHCT. Conditioning regimen consisted of fludarabine 30 mg/m(2)/day for 6 days and anti-T-lymphocyte globulin (ATG) 10 mg/kg/day for 4 days as immunosuppressive. Ara-C or Bu or melphalan were used as the cytoreductive component. All transplants were performed using HLA-identical sibling donors' peripheral blood hematopoietic cells, after priming with filgrastim. Post-transplant GvHD prophylaxis was achieved with CsA alone in 10 patients, and with CsA plus mycophenolate mofetil in the last three patients. RESULTS: Median follow-up is 3 months (range, 0-20) for all the patients and 6 months (range, 2-15) for the live patients. Donor chimerism was shown in 10 patients, not regarding any pretransplant feature. DLIs were performed in seven patients after transplantation and two of them achieved complete chimeric status and molecular remission. Two CML patients in blastic phase (CML-BP), and the primary refractory secondary AML patient did not respond to procedure. In four patients, drug therapy in conventional doses was added to post-transplant DLIs for their relapsed or refractory diseases. Two patients with AML in second CR, and another CML-BP patient, relapsed or progressed after transplantation. A patient with CML-BP achieved CR and full donor chimerism after transplantation, but developed refractory post-transplant lymphoproliferative disease in the 19th month. Two patients with refractory AML, one patient with relapsed ALL and two patients with CML in chronic phase were in complete chimeric status and free of disease signs. Acute GvHD, Grade II-III, was observed in five patients, and two of them developed secondary progressive chronic GvHD subsequently. We observed one early death in a platelet transfusion refractory blastic phase CML patient due to intracranial hemorrhage. Procedure-related severe toxicity was not observed, either in standard-risk patients or stem-cell donors. DISCUSSION: Establishing engraftment with donor chimerism was the first successful step in this approach. The second step, which was the result of the graft-versus-malignancy effect, could be seen in most of the patients, but was not sustained in all of them because of the aggressiveness of their malignancy. It can be suggested that the immunotherapeutic efficacy of this approach could be more successful, and with acceptable toxicity, when performed in patients with minimal residual disease. The role of NMA conditioning, and of the treatment in standard disease indications, remains to be determined in further studies.


Subject(s)
Graft Survival/immunology , Graft vs Tumor Effect/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/immunology , Immunosuppressive Agents/therapeutic use , Transplantation Conditioning/methods , Adult , Bone Marrow Purging/adverse effects , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/physiopathology , Hematologic Neoplasms/physiopathology , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cells/cytology , Host vs Graft Reaction/immunology , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/physiopathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/physiopathology , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Myeloablative Agonists/therapeutic use , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Remission Induction/methods , Secondary Prevention , Transplantation Chimera/immunology , Transplantation, Homologous , Treatment Failure
14.
Bone Marrow Transplant ; 25(12): 1229-32, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10871726

ABSTRACT

Fifty-three patients with standard risk leukemia who underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from their HLA-identical siblings were analyzed for engraftment, incidence and severity of GVHD, and relapse rate. Standard risk leukemia was defined as AML in first complete remission or CML in first chronic phase within the first year after diagnosis. The median age was 34.5 years (range 13-47). Stem cells were mobilized by using 10 microg/kg G-CSF subcutaneously for 5 days. A median of 5. 7 (2.1-21.4) x 106/kg CD34+ cells was collected over a median of 2 (range 1-5) apheresis procedures. Cyclosporin A (CsA) plus short-course MTX were used for GVHD prophylaxis. Recovery to granulocytes >0.5 x 109/l and platelets >20 x 109/l occurred at a median of day +13 (range 8-32) and +13 (range 8-51), respectively. Day +100 transplant-related mortality was 13.2% (7/53). Acute GVHD occurred in 20 of 49 (41%) evaluable patients and only six (12.3%) of them had severe disease (grade III-IV). Chronic GVHD occurred in 30 of 42 (71.4%) evaluable patients. Relapse rate at 2 years was 7. 5%. The median overall and leukemia-free survivals were 22 (4-44) and 20 (3-44) months, respectively. Estimated 4 year leukemia-free and overall survival rates were 60% and 62%, respectively. In conclusion, alloPBSCT in standard risk leukemia seems to be associated with a low relapse rate and no increased risk of acute GVHD, but there is a trend for higher incidence of cGVHD. Bone Marrow Transplantation (2000) 25, 1229-1232.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia/therapy , Adolescent , Adult , Female , Humans , Leukemia/pathology , Male , Middle Aged , Recurrence , Transplantation, Homologous , Treatment Outcome , Turkey
15.
Cytotherapy ; 2(4): 259-65, 2000.
Article in English | MEDLINE | ID: mdl-12042035

ABSTRACT

BACKGROUND: We analysed the effects of rhG-CSF (Amgen-Roche, USA) on serum changes of four soluble adhesion molecules (SAM) (sICAM-1, sL-Selectin, sE-Selectin and sCD44) in healthy peripheral allogeneic stem-cell transplantation donors and their correlation with acute GvHD and effect on engraftment kinetics. METHODS: Serum SAM of 15 consecutive healthy HLA identical-sibling donors (median age 30 years, male:female ratio, 7:8) were monitored using a commercial ELISA Kit (Bender Med, Austria) prior to, on the day of first apheresis and 24 h after the cessation of rhG-CSF (10 microg/kg/day s.c. on 5 days) administration. Leukapheresis was started on the fifth day of rhG-CSF administration, using a continuous-flow blood separator (Cobe Spectra, COBE BCT, Inc, Lakewood, CO). Apheresis cycles were continued daily until a target of 4.0 x 10(6) CD34(+) cells/kg was reached. RESULTS: The results indicate a steady rise of sL-Selectin, sE-Selectin, and sCD44, but not of sICAM-1. Median number of mononuclear cells (MNC) and CD34(+) cells transfused were 7.7x 10(8)/kg and 6.0 x 10(6)/kg, respectively. There was a near-significant correlation between the sL-Selectin levels and CD34(+) cell yield (r = 0.49, 0.06). Median granulocyte and platelet engraftment days were 11 (10-18) and 12 (9-33), respectively. There was a significant inverse correlation between the CD34(+) cell dose and granulocyte levels (r = -0.68, p = 0.022), but not for platelet engraftment. The only correlation between SAM levels and engraftment was for sICAM-1 levels. Increasing sICAM-1 levels were a sign of prolonged neutropenia (r = 0.72, p = 0.011). No correlation between the apheresis day serum levels of adhesion molecules and acute GvHD was documented. DISCUSSION: Analysis of sICAM-1, sL-Selectin, sE-Selectin and sCD44 levels during allogeneic PBSC apheresis did not reveal any significant effect on engraftment and GvHD, except the correlation of sL-Selectin levels and collected CD34(+) cells. More research and data about the role of not only SAM levels, but also antigenic expression of SAM are required to enlighten leukocyte-endothelial cell interactions and egress of stem cells during G-CSF administration.


Subject(s)
Blood Donors , E-Selectin/blood , Granulocyte Colony-Stimulating Factor/pharmacology , Hyaluronan Receptors/blood , Intercellular Adhesion Molecule-1/blood , L-Selectin/blood , Stem Cell Transplantation/methods , Adult , Antigens, CD34/analysis , Antigens, CD34/immunology , Enzyme-Linked Immunosorbent Assay , Female , Graft vs Host Disease , Humans , Leukapheresis , Male , Middle Aged , Recombinant Proteins , Solubility , Stem Cells/cytology , Stem Cells/drug effects , Time Factors , Transplantation, Homologous
16.
Clin Nucl Med ; 24(11): 842-4, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10551462

ABSTRACT

PURPOSE: The influence of patient posture on the incidence and severity of gastroesophageal reflux is well known. Scintigraphic imaging, however, is routinely performed with the patient lying in the supine position, because current gamma camera designs do not allow for changes to the angle of the patient table. METHODS: To overcome this difficulty and to increase the diagnostic sensitivity of scintigraphy, we used an alternative patient position. Twenty-seven adult patients (eight men, 19 women; mean age, 47.5+/-11.5 years) with gastroesophageal reflux disease were prospectively studied consecutively using two body positions, the supine and the knee-chest positions. Each consisted of dynamic acquisition of 450 seconds. An entire study for each patient required only 15 minutes. Images were interpreted qualitatively by three observers. RESULTS: Although gastroesophageal reflux was positively identified in only 9 of 27 (33%) patients using the supine position, 20 of 27 (74%) patients were shown to have gastroesophageal reflux in the knee-chest position (P < 0.05). No reflux was detected in seven patients using both positions. In five patients, whose study results were positive using both positions, the number of reflux episodes was greater in the knee-chest position compared with the supine position. CONCLUSION: The knee-chest position increases the diagnostic efficiency of gastroesophageal reflux scintigraphy.


Subject(s)
Gastroesophageal Reflux/diagnostic imaging , Posture , Female , Humans , Male , Middle Aged , Organotechnetium Compounds , Phytic Acid , Radionuclide Imaging , Radiopharmaceuticals , Supine Position , Time Factors
17.
J Hepatol ; 31(2): 202-9, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10453930

ABSTRACT

BACKGROUND/AIMS: Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS: A total of 151 patients received an allogeneic hematopoietic stem cell transplantation at the Department of Hematology-Oncology, University of Ankara, between June 1989 and June 1998. Among these, eight HBs-Ag positive and four HBs-Ag negative recipients received a product from a hepatitis B virus positive donor. The median follow-up period for these 12 patients was 13.2 months. RESULTS: Three of the eight HBs-Ag positive recipients died (one from hepatic failure); of the remainder, two are HBs-Ag negative, two HBs-Ag positive with normal liver injury tests and one HBs-Ag positive with elevated ALT levels. Of the four HBs-Ag negative recipients who received stem cells from a hepatitis B positive donor, two died; none of the patients in this group became HBs-Ag positive after transplantation. CONCLUSION: Hepatitis B virus infection is a common problem in patients being considered for allogeneic hematopoetic stem cell transplantation, especially in areas where hepatitis B virus infection is endemic. We believe that the presence of HBs-Ag positivity is not an absolute contraindication for allogeneic hematopoetic stem cell transplantation unless the hepatitis B virus is in a replication phase.


Subject(s)
Carrier State/immunology , Hematopoietic Stem Cell Transplantation , Hepatitis B Surface Antigens/blood , Hepatitis B virus/pathogenicity , Hepatitis B/prevention & control , Adolescent , Adult , Carrier State/virology , Contraindications , Fatal Outcome , Hepatitis B/immunology , Hepatitis B/transmission , Humans , Immunity, Innate , Immunosuppression Therapy , Immunotherapy, Adoptive , Male , Middle Aged , Virus Replication
18.
Biol Blood Marrow Transplant ; 5(1): 28-35, 1999.
Article in English | MEDLINE | ID: mdl-10232738

ABSTRACT

To detect the effect of the stem cell source, allogeneic peripheral blood stem cell transplantations (alloPBSCTs) performed between 1995 and 1997 from human leukocyte antigen (HLA)-identical siblings in 40 patients with acute and chronic hematological disorders were compared with a historical group of 40 patients with similar variables who had received allogeneic bone marrow transplants (alloBMTs) between 1993 and 1995. Patients in both groups were identical except that both the recipient and the donor ages were, on average, higher in the alloPBSCT group (26 vs. 36 [p = 0.005] and 27 vs. 32 [p = 0.024], respectively). Patients received similar therapy excluding posttransplant granulocyte colony-stimulating factor administration (97% in alloBMT vs. 12.5% in alloPBSCT). The median time to reach neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L was 13 and 14 days, respectively, in patients receiving alloPBSCTs compared with 19 and 27 days in patients receiving alloBMTs (p = 0.0014 and p = 0.0002). The alloPBSCT group required similar transfusions of red blood cells or platelets. The incidence of grade II-IV acute graft-vs.-host disease (aGVHD) was similar in both groups. However, chronic GVHD (cGVHD) of all grades developed in 78.1% of patients in the alloPBSCT group after a median follow-up period of 12.5 (range 0.5-34) months. In alloBMT recipients, cGVHD of all grades developed in 21.4% after a median follow-up period of 38 (range 0.5-62) months (p = 0.00001). Day 100 transplant-related mortality was also similar: 20% (8 of 40) in the alloBMT patients and 17.5% (7 of 40) in the alloPBSCT group. Although not statistically significant, a relatively higher relapse rate occurred in the alloBMT group (21.4 vs. 10.7%). The estimated disease-free survival in month 24 was 51.3% for alloBMT and 54.6% for alloPBSCT, and the estimated overall survival in month 24 was 56.1% for alloBMT and 64.6% for alloPBSCT. In conclusion, this retrospective comparison suggests that alloPBSCT from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of aGVHD, but a high incidence of cGVHD.


Subject(s)
Bone Marrow Transplantation , Graft vs Host Disease/epidemiology , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Female , Graft Rejection , Humans , Incidence , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Opportunistic Infections/drug therapy , Recurrence , Retrospective Studies , Transplantation, Homologous , Treatment Outcome , Turkey/epidemiology
19.
Transfus Sci ; 20(1): 69-71, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10621563

ABSTRACT

Forty-five patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) were evaluated in order to investigate any relationship between CD34+ cell dose given and hematological recovery. Granulocyte counts > 1.0 x 10(9)/L and platelet > 50 x 10(9)/L were considered as hematological recovery. Three different regimens were used for mobilization, by adjusting the recombinant granulocyte colony stimulating factor (rhG-CSF, Roche) dose. The first group (n = 3), whose donors mobilized with 5 micrograms/kg/d s.c. rhG-CSF received a mean of 5.9 x 10(6)/kg (95% confidence interval for mean (CI); 2.4-9.3) CD34+ cells. The second group (n = 37), mobilized with 10 micrograms/kg/d s.c. rhG-CSF and the third group (n = 5) mobilized with 15 micrograms/kg/d s.c. rhG-CSF, received a mean of 5.7 x 10(6)/kg (95% CI; 4.6-6.75) and 6.56 x 10(6)/kg (95% CI; 4.57-8.55) CD34+ cells, respectively. CD34+ cell dose was 5.82 x 10(6)/kg (95% CI; 4.97-6.68) for all the patients. All patients received rhG-CSF from day +1 until attaining granulocyte count > 1.0 x 10(9)/L for three consecutive days. Median granulocyte and platelet engraftment days for the whole group was 15 (range; 11-44) and 14 (11-54) days respectively. There was a close correlation (r = -0.301, p < 0.05) between the CD34+ cell dose and granulocyte recovery for the whole group. When these analyses were performed separately within groups, this correlation was also found significant for the first group (r = -0.99, p < 0.05) for granulocyte recovery. On the contrary the same analysis did not reach significance for the other groups, nor for platelet recovery for the whole group (r = 0.039, p = 0.821). We calculated a minimum dose of 4 x 10(6)/kg CD34+ cells for a safe alloPBSCT. There was no difference between patients who received more than 5 x 10(6)/kg CD34+ cells, and those who received more than 2 x 10(6)/kg and less than 5 x 10(6)/kg CD34+ cells. In conclusion, we have demonstrated a correlation between the CD34+ cell dose given and faster hematological recovery for alloPBSCT patients.


Subject(s)
Antigens, CD34/blood , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Cell Count , Child , Child, Preschool , Dose-Response Relationship, Immunologic , Female , Graft Survival/immunology , Humans , Male , Transplantation, Homologous
20.
Med Oncol ; 15(3): 183-90, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9819795

ABSTRACT

Various regimens have been explored in the treatment of acute nonlymphoblastic leukaemia (AML), but so far none has been shown to be superior. Here we report on a comparison of three widely used protocols defined by Berman (Group 1), MRC AML 10 (Group 2), and Arlin (Group 3). Group 1 includes cytosine arabinoside (Ara-C) (100 mg/m2/d, days 1-7) and idarubicin (Ida) (12 mg/m2/d, days 1-3) for induction, and Ara-C (200 mg/m2/d, days 1-6) and Ida (15 mg/m2/d, day 1) twice for consolidation. Group 2 includes Ara-C (200 mg/m2/d, days 1-10), daunorubicin (Dnc) (50 mg/m2/d, days 1, 3, 5) and etoposide (VP16) (100 mg/m2/d, days 1-5) for induction. The first consolidation therapy consisted of the same schedule except for Ara-C given on days 1-8. The second consolidation regimen consisted of Ara-C (200 mg/m2/d, days 1-8), VP16 (100 mg/m2/d, days 1-5) and amsacrine (100 mg/m2/d, days 1-5). Mitoxantrone (Mitox) (10 mg/m2/d, days 1-5) and Ara-C (200 mg/m2/d, days 1-3) were given as the third consolidation therapy. Group 3 was identical to Group 1 except for Ida being replaced with Mitox. During the study period 99 patients were enrolled and 34 were allocated randomly to Group 1, 36 to Group 2, and 29 to Group 3. Except for age distribution all patients' characteristics were similar between the groups. As there were more elderly patients in Group 1, time to complete remission (CR) was longer in this group as they needed more second induction. Induction deaths were 9.7%, 12.9% and 14.8% in Groups 1, 2 and 3, respectively. Patients in Group 2 received a higher amount of Ara-C compared with the other groups (P < 0.001). After a median follow-up period of 45 months (1-67 for survivors) an advantage in Group 1 was observed. Relapse-free survival (RFS) was better in Group 1 (P = 0.014) at 3 years. Fourteen of the patients were transplanted (11 allografts, 3 autografts). When patients with transplants were excluded, overall survival was longer in Group 1 both at 3 years and 5 years (P = 0.05). In conclusion, despite patient advanced age and lower dose of Ara-C, the idarubicin-containing treatment was superior to the other regimens.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Aged , Amsacrine/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Idarubicin/administration & dosage , Male , Middle Aged , Mitoxantrone/administration & dosage , Remission Induction , Survival Analysis
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