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Biomedical subjects

D Nemet

Publications and source records attributed to D Nemet.

At least 37 records · Page 2Linked to original sources

Quantity and origin of transplanted autologous blood cells are independent factors associated with speed of postransplant hematological reconstitution.

AIM: Multivariate analysis of the prognostic significance of clinical and laboratory parameters on hematological recovery after autologous hematopoietic stem cell transplantation. METHODS: Sixty-two patients suffering from hematological and non-hematological malignancies entered the study. After conditioning therapy, 28 patients received bone marrow stem cells, 21 received peripheral blood stem cells, and 13 received both. The dynamic of hematological engraftment was calculated as recovery probability of leukocytes and neutrophils. Statistics was done using Kaplan-Meier method and multivariate Cox's proportional regression. RESULTS: Numerous clinical and laboratory parameters correlated with hematological recovery, but only two variables were found to be independently associated. Faster reconstitution correlated with greater number of progenitors and patients who received bone marrow cells recovered significantly later than others. Faster recovery could be expected in patient s receiving >13x10(4) CFU-GM/kg body weight, and significantly slower in those receiving <8.5x10(4) CFU-GM/kg. CONCLUSION: The quantity of progenitor cells and transplant type are variables significantly associated with the speed of postransplant engraftment, but these two parameters are mutually independent. The number of stem cells estimated by CFU-GM assay is a good and reliable routine test for predicting hematopoietic recovery.

Acute Disease↗

Thiorphan stimulates clonal growth of GM-CFU in short-term cultures of bone marrow from a healthy donor and from patients with non-Hodgkin lymphoma.

Thiorphan, a specific inhibitor of membrane neutral endopeptidase (NEP, EC 3.4.24.11) also known as the common acute lymphoblastic leukemia antigen (CALLA, CD10) was added into short-term clonal cultures of the buffy coat concentrates of human bone marrow obtained from a healthy donor (six experiments) and from ten patients with non-Hodgkin lymphoma (NHL) (eight in complete remission, one in partial remission and one in relapse). Thiorphan concentrations ranged from 10(-5) to 10(-13) M. Nanomolar and higher concentrations of the drug mildly stimulated the granulocyte-macrophage colony-forming unit (GM-CFU) counts in the cultures of normal bone marrow, reaching the significance at 10(-7) M. Meaningful alterations of the GM-CFU counts were noted in 31 of 79 thiorphan-treated cultures of NHL bone marrow (39%). In those cultures the stimulatory effects (33%) outnumbered the inhibitory ones (6%). The stimulatory effects occurred mainly in the bone marrow samples of the patients with highly malignant NHL. The observations are compatible with the idea that the membrane endopeptidase (CALLA, CD10) participates in processes controlling the proliferation and differentiation of hematopoetic cells by cleaving the neuropeptides and related hemoregulatory peptides.

Bone Marrow↗

Relation between urinary cytology abnormalities and cyclosporine A therapy in bone marrow transplant recipients.

The aim of the study was to determine the relationship, if any, between abnormalities in urinary cytology and the administration of cyclosporine A in bone marrow transplant recipients. Specific attention was given to the presence of tubular cells with round inclusions (TCRI). Two bone marrow transplant recipient groups were studied: one with allogeneic bone marrow transplantation (BMT) (20 patients) who were treated with cyclosporine A, and the other with autologous BMT (12 patients) who did not receive cyclosporine A. Urinary cytology showed TCRI in 41.66% of the patients after autologous BMT and in 80% of the patients after allogeneic BMT. In the group of patients treated with allogeneic BMT, the occurrence of TCRI was associated with a high incidence of glycosuria and was followed by an increase in the blood level of cyclosporine A, an increase in the serum creatinine concentration and a decrease in the creatinine clearance. These results demonstrated that TCRI, although related to, were not found to be exclusively specific to the administration of cyclosporine A.

Adult↗

Treatment of chronic myeloid leukemia in relapse after umbilical cord blood transplantation.

Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells for allotransplantation. Donor-derived buffy coat cells are considered optimal treatment for leukemia relapses after transplantation of allogeneic bone marrow. Experience with relapses after UCB transplants are sparse. Here we report a girl who received an UCB transplant for chronic myeloid leukemia, relapsed after three years, failed to respond to donor buffy coat cells, but achieved a complete hematologic, cytogenetic, and molecular remission on interferon-alpha.

Child, Preschool↗

Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy.

From October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.

Adolescent↗

Anxiety as a possible predictor of acute GVHD.

In order to determine the influence of anxiety on the development of BMT complications and survival, we analysed data on 35 consecutive patients undergoing BMT in our Centre between June 1992 and December 1994. All patients received bone marrow from HLA-identical MLC non-responsive siblings. For GVHD prophylaxis, all patients received cyclosporin (CsA) and short methotrexate (MTX). The diagnosis and severity of acute GVHD were defined according to the Seattle Transplant Team criteria. The patients were tested with the Spielberger STAI test as a measure of anxiety as a state (STAI-S) and as a trait (STAI-T). The STAI-S/1 and STAI-T/1 were performed during the first week of isolation (day -5 to day -3 prior BMT) and STAI-S/2 and STAI-T/2 at the end of the discharge from laminar air flow units (day +35 to day +40 post-transplant). During isolation all patients had daily psychiatric support. Out of 35 patients, 31 (89%) fulfilled the STAI-S and STAI-T during the first week and at discharge from laminar air flow isolation. The level of anxiety at the beginning of isolation as measured by STAI-S/1 and STAI-T/1 tests had been significantly higher in patients who subsequently developed acute grade II-IV GVHD as compared to patients with GVHD grade 0-I (P < 0.001), irrespective of age, sex or stage of the disease prior to BMT. In those patients who died, the STAI-S/1, STAI-T/1 and STAI-T/2 tests had been almost identical to those of surviving patients, while STAI-S/2 had been significantly higher (P = 0.034). These data clearly indicate an association between the level of anxiety and the risk for BMT complications, but this should be confirmed in further controlled clinical trials.

Adolescent↗

Malignant germ cell tumors of the ovary: a study of 20 cases.

In a study of 20 patients diagnosed with malignant ovarian germ cell tumors between 1961 and 1993, clinical and pathologic findings were evaluated. Of the 20 patients, seven (35%) had dysgerminoma, two (10%) endodermal sinus tumor, three (15%) malignant teratoma, one (5%) malignant struma ovarii, one (5%) primary ovarian carcinoid, two (10%) benign teratoma with malignant transformation, and four (20%) combination germ cell tumor. Twelve patients (60%) had stage IA, five (25%) stage IC, and three (15%) stage IIIC. Twelve patients (60%) underwent conservative surgery and eight (40%) had at least bilateral salpingo-oophorectomy. At follow-up, 18 patients (90%) were alive free of disease, one (5%) had died of disease, and one (5%) had died of intercurrent disease. The actuarial 5-year survival rate was 93.3%. It is concluded that for young women who wish to preserve child-bearing capacity, regardless of the stage of the tumor, fertility-preserving surgery with complete surgical staging followed, if necessary by cisplatin-based combination chemotherapy is an appropriate and definitive treatment in the absence of involvement of the contralateral ovary and uterus. For patients in whom child-bearing capacity is not an issue, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy with complete staging, followed if necessary by chemotherapy.

Adolescent↗

An autopsy study of systemic fungal infections in patients with hematologic malignancies.

The aim of this study was to determine the incidence of fungal infections detected on autopsy in a group of 40 patients with hematologic malignancies treated with intensive chemotherapy or bone marrow transplantation, and to evaluate the risk factors for fungal infections. A control group included 38 patients with nonhematologic diseases and without granulocytopenia but with at least one of the known risk factors for fungal infections. Standard histopathological and microbiological methods were used. A higher incidence of invasive fungal infections was found in patients with hematologic malignancies as compared to the control group (p < 0.01). The predominant causes of fungal infections were Candida albicans and Aspergillus spp. The incidence of fungal infections caused by Aspergillus was higher (p < 0.05) in patients with hematologic malignancies than in the control group. The independent risk factors for fungal infections were fungal colonization, number of antibiotics and duration of antibiotic therapy, duration of fever and skin rash. A higher proportion of fungal infections was diagnosed on autopsy than during the patients' life (p < 0.01).

Adolescent↗

Granulocyte-monocyte colony forming unit content of autologous bone marrow transplants in patients with haematological malignancy.

Cell viability and number of granulocyte-monocyte colony forming units (CFU-GM) were systematically assessed in 57 patients who had undergone transplantation of the autologous bone marrow for treatment of haematologic malignancies. Bone marrow cell cultivation in agarose with feeder layers appeared inferior to that performed in agarose with recombinant human granulocyte-monocyte colony stimulating factor and methylcellulose with phytohaemaglutinin leukocyte-conditioned medium. Since the transplant cells were frozen in liquid nitrogen between harvesting and reinfusion, the following samples were tested: buffy coat cells, buffy coat cells immediately after addition of dimethylsulphoxide, cell sample that had been frozen for 24 hours, and frozen transplant cells at the time of thawing and transplantation. Each procedural step decreased both cell viability and the number of CFU-GM, but since the lymphohaematologic recovery in all patients followed the pattern reported in the literature for high-quality transplants, we concluded that our transplants retained the necessary number of progenitor cells. It appears that the best strategy for dynamic assessment of the transplant quality would be to perform tests after every step of the transplant processing. Cell viability and number of progenitors per body weight in transplants were also found to be associated with probability of neutrophil reconstitution after bone marrow reinfusion.

Adolescent↗

Serum enzyme activities following long-distance running: comparison between Ethiopian and white athletes.

Ethiopian runners are famous for their achievements in long-distance running. The recent immigration of Ethiopians to Israel provided an opportunity to compare some physiological variables between elite Ethiopian and white Israeli runners. Six Ethiopian and five white Israeli runners, aged 20 to 40 years, were studied before and after an 11 km race. Venous blood was sampled from each runner prior to the race, and 1 h, 48 h, and 5 days following the race. The activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured, and levels of serum electrolytes, urea, creatinine, phosphorus, albumin, cholesterol, and alkaline phosphatase were also determined. CK activity rose 2.6-fold with a peak 5 days after the race. LDH and AST levels rose as well (1.4-1.3-fold, respectively). Significant elevations also occurred in serum phosphorus, uric acid, and creatinine concentrations 1 h after the race. In contrast to previous studies in which higher enzyme activities were reported in blacks, we did not detect any difference in serum enzyme values between black and white runners.

Adult↗

Dose intensity of cisplatin-based chemotherapy in epithelial ovarian carcinoma. An important factor affecting survival.

Forty-three patients with epithelial ovarian carcinoma, were treated by cyclophosphamide and cisplatin (CP) following initial laparotomy. The mean dose intensity (DI) and mean relative dose intensity (RDI) respectively were for cyclophosphamide: 166.69 mg/sqm/week and 0.67, and for cisplatin: 16.29 mg/sqm/week and 0.65. The mean average relative dose intensity (ARDI) was 0.66. The three-year survival for all patients was 44.3%. The three-year survival for patients receiving cyclophosphamide with a RDI of more than median value was 63.82%, while for patients receiving cyclophosphamide with a RDI of less than median value three-year survival was 26.3% (p < 0.02). The three-year survival for patients receiving cisplatin with an RDI of more than median value was 62.01%, as compared to 24.17% for patients receiving cisplatin with a RDI of less than median value (p < 0.02). The three-year survival for patients receiving the CP regimen with an ARDI of more than median value was significantly higher than that for patients receiving the CP regimen with an ARDI of less than median value (63.82% versus 26.03%, p < 0.02). Dose intensity of cisplatin-based chemotherapy in epithelial ovarian carcinoma is an important factor affecting survival.

Adult↗

Autologous bone marrow transplantation for haematological malignancies--experiences of the centre of Zagreb.

From April 1988 to May 1993, 71 patients (32 acute myelogenous leukaemia [AML], 24 acute lymphoblastic leukaemia [ALL], 7 Hodgkin's disease [HD], 5 non-Hodgkin lymphoma [NHL], 2 neuroblastoma, 1 chronic myelogenous leukaemia [CML]) were treated with myeloablative therapy followed by reinfusion of cryopreserved autologous bone marrow (ABMT). The majority of patients with acute leukaemia were in first complete remission (CR), while 11 AML patients and 9 ALL patients were in advanced stage of the disease (> I CR or relapse). The BM was reinfused without purging. The conditioning regimen for all ALL and proportion of AML patients consisted of cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TB) in a total dose of 12 Gy. 18 AML patients received busulfan 16 mg/kg instead of TBI. Leukaemia-free survival (LFS) for first CR AML patients was 48% at 43 months with the median follow-up of 17 months. Probability of relapse was 44%. LFS for advanced AML was only 9% and the probability of relapse 89%. LFS for first CR ALL patients was 72% at 53 months with the median follow-up of 15 months, while probability of relapse was only 23%. For advanced ALL, LFS was 32% at 33 months and probability of relapse 64%. Probability of toxic death for first CR patients was 11%. We found a predictive value of viability testing and in vitro CFU-GM assay for haematologic recovery after ABMT. We conclude that ABMT with cryopreserved BM is a relatively safe method for consolidation therapy of AL. The results of treatment are encouraging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Granulosa cell tumor of the ovary: a study of 18 cases.

In a study of 18 patients diagnosed with ovarian granulosa cell tumor between 1961 and 1992, clinical and pathologic findings were evaluated. Of the 18 patients, 15 (83.3%) were diagnosed in Stage I and three (16.7%) in Stage III or IV. Six patients (33.3%) underwent conservative surgery and in 12 (66.7%) total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. At follow-up three patients (16.6%) had died of disease, three, 16 and 288 months, respectively, after initial surgery. The actuarial 5-year survival rate for Stage I was 100%, while that for Stages III and IV combined was 33.3% (P < 0.05). It is concluded that for patients with Stage IA, unilateral oophorectomy seems to be adequate treatment and for those with more than Stage IA, surgery should include total abdominal hysterectomy and bilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy is advocated for patients in whom spread of tumor beyond the ovaries has occurred.

Adolescent↗

High incidence of conservative RAS mutations in acute myeloid leukemia.

RAS mutations are found in about 25% of acute myeloid leukemia (AML) cases. The importance of these changes is unknown. If RAS mutations confer growth advantage to leukemia subclones in which they emerge, substantially more nonconservative than conservative mutations should be found. The incidence of conservative mutations was not reported previously. We sequenced N-RAS and K-RAS codons 12 and 13 and N-RAS codon 61 in 20 subjects with newly diagnosed AML. Four nonconservative N-RAS mutations and 4 conservative K-RAS mutations were found. There were no differences between subjects with AML and nonconservative RAS mutations and those with conservative or without RAS mutations. Additional studies are needed to examine the incidence of conservative RAS mutations in subjects with AML.

Acute Disease↗

Correlation of morphological FAB classification and immunophenotyping: value in recognition of morphological, cytochemical and immunological characteristics of mixed leukaemias.

Correlation between the FAB classification and immunophenotype was studied in 169 consecutive adult patients with acute leukaemia (AL). The lineage of leukaemic cells could be determined in the majority of cases, whereas 3 patients (1.8%) remained unclassified. In 22 out of 71 patients (31%) with acute myeloid leukaemia (AML) FAB M1 and M2 types, and in 5 out of 16 patients (31%) with chronic myeloid leukaemia (CML) in myeloid blast crisis, leukaemic cells did not express myeloid lineage-related markers, indicating asynchronous expression of cell markers in a substantial proportion of patients. Flow cytometric two-colour immunofluorescence revealed mixed AL immunophenotype in 6 out of 169 patients (3.4%). This group included five CD2+AML (5% of AML tested) and one undifferentiated AL expressing CD10(CALLA), CDw65(VIM-2). The former group included FAB M1, M2, M3 and M4 forms of AML with a single cell population, and an AML M2 patient with both cytochemically and immunologically two separate populations of leukaemic cells. This further illustrates the heterogeneity of the target cell(s) for leukaemogenesis and the level of differentiation of AML cells. However, there was no difference in the treatment response and the remission duration between AML patients and patients with mixed phenotype AML.

Acute Disease↗