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Biomedical subjects

T de Witte

Publications and source records attributed to T de Witte.

At least 127 records · Page 7Linked to original sources
PubMed1990

Continuous intravenous administration of daunorubicin and cytarabine for remission induction of poor risk acute myelogenous leukaemias and myelodysplastic syndromes.

Seventeen consecutively admitted poor risk acute myeloid leukaemia (AML) patients and 4 patients with myelodysplastic syndrome (MDS) were treated with a remission-induction regimen consisting of a 7-day continuous intravenous infusion of conventional doses of cytarabine and of three 24-h constant rate infusions of daunorubicin administered intermittently on days 1, 3 and 5. The diagnoses were: relapsed primary AML in 6 patients, secondary AML in 11 patients (9 untreated, 2 relapsed) and MDS in 4 patients. The median age was 50 yr. Five of 6 patients with relapsed primary AML, 3 of 11 patients with secondary AML and 2 of 4 patients with MDS achieved complete remission (CR). The overall CR rate was 48% with a median remission duration of 5 months (range: 0.25-20 months). Few acute toxic side effects were observed thanks to the constant rate of infusion of daunorubicin.

Acute Disease↗
PubMed1989

Diabetes insipidus associated with leukaemia.

Three cases of leukaemia complicated by pituitary diabetes insipidus are presented. In one patient diabetes insipidus developed five months before acute myelomonocytic leukaemia became apparent. The two other patients suffered from acute myelomonocytic leukaemia and from a blastic transformation of chronic myeloid leukaemia. In one case a transient cure of diabetes insipidus was obtained after intrathecal chemotherapy and irradiation of the skull.

Adult↗
PubMed1988

Irradiated donor buffy coat following T cell-depleted bone marrow transplants.

Twenty patients aged 27-47 years (median, 35 years) with hematological malignancies, treated with T cell-depleted bone marrow transplantation received in a pilot study five donations of 15 Gy irradiated donor buffy coat cells at days +1, +3, +5, +7, +14 in order to prevent rejection and leukemic relapse. Patients were conditioned with etoposide, cyclophosphamide and 12 Gy fractionated total body irradiation and given cyclosporine postgrafting. Donor bone marrow was T cell-depleted (median 3% remaining T cells) by counterflow elutriation. All patients engrafted. Fourteen (70%) are alive. Two are living with relapse, 12 (60%) are alive and well without any signs of disease, 2-27 months (median, 9 months) post-transplant. Three patients died of interstitial pneumonitis and/or graft-versus-host-disease; three died of relapse. This pilot study supports previous animal data. Repeated infusions of 15 Gy irradiated donor buffy coat are feasible and do not appear to increase transplant related mortality. Whether this approach ultimately will reduce the rate of rejection and relapse following T cell depletion needs to be confirmed in a larger, prospective study.

Adult↗
PubMed1988

A new multichamber counterflow centrifugation rotor with high-separation capacity and versatile potentials.

A new closed system for counterflow centrifugation (elutriation) is described. The system was developed to increase the capacity of counterflow centrifugation in order to be able to separate bone marrow intended for allogeneic bone marrow transplantation within 3 h. The rotor has the capacity for up to four separation chambers, offering the possibility of separating either a single-cell suspension under equal or differing conditions, or four different suspensions simultaneously. Profiles of low-density nucleated cells from normal blood were shown to be identical after elutriation in four different chambers. Leucocytes could be depleted from platelet concentrates without significant loss. Most (98%) of the lymphocytes were removed from donor marrow intended for transplantation within 3 h and the recovery of myeloid and erythroid clonogenic cells in the graft was similar to that obtained from the standard single chamber centrifuge.

Bone Marrow Cells↗
PubMed1987

Long-term oral ciprofloxacin for infection prophylaxis in allogeneic bone marrow transplantation.

The efficacy of oral ciprofloxacin to prevent bacterial infections during the first three months after allogeneic bone marrow transplantation (BMT) was assessed prospectively. Twenty-three recipients of lymphocyte depleted marrow grafts received ciprofloxacin orally, 500 mg twice daily for 90 days after BMT. Nine patients had no infections during ciprofloxacin prophylaxis; in the remaining 14 patients 19 febrile episodes occurred. No infections could be attributed to Gram-negative rods nor to fungal micro-organisms on the basis of the micro-organisms isolated. One infection, a pneumonia due to Bacteroides melaninogenicus, proved to be fatal. Allergic skin reactions were observed in three patients, but neither hematological nor nephrological side-effects could be substantiated in patients who were treated concomitantly with cyclosporine. Prolonged administration of ciprofloxacin turned out to be safe and effective in preventing serious aerobic bacterial infections during the first three months after BMT.

Administration, Oral↗
PubMed1987

Prognostic factors in adult patients with acute leukemia at first relapse.

The case histories of 252 adolescent and adult patients with acute leukemia diagnosed and treated between 1975 and 1985 are analyzed with special attention to prognostic factors determining the second complete remission (CR) rate. A first CR was achieved in 65% of cases, 60% for acute myelogenous leukemia (AML), and 75% for lymphoblastic leukemia (ALL). In 86 patients a relapse occurred (50 AML, 36 ALL), and 50% of them entered a second CR after reinduction therapy. Median survival after first relapse of these reinduction-responders was significantly prolonged in comparison to the reinduction-nonresponders for both AML (15 versus 2 months) and ALL (11 versus 3 months). Median duration of the first CR of the reinduction-responders was significantly longer than that of the second CR (13 versus 6 months). The major determinant for the probability to obtain a second CR after reinduction therapy was the duration of the first CR. The latter was significantly longer in the reinduction-responders than in the nonresponding group (13 versus 5 months). Furthermore patients younger than 40 years, and those who relapsed after ending the maintenance therapy, tended to have better chances to achieve a second CR. Rapid achievement of the first CR, and sex of the patients seemed not to be of predictive value. The authors conclude that aiming for a second CR is worthwhile in young patients who relapse after a long first CR.

Adolescent↗
PubMed1987

Infusion-rate independent cellular adriamycin concentrations and cytotoxicity to human bone marrow clonogenic cells (CFU-GM).

The effect of adriamycin (ADM) infusion-rate on cellular ADM concentrations and on clonogenicity of human haematopoietic cells was studied in vivo and in vitro. In patients an ADM dose of 30 mg m-2 was administered as a bolus injection, or as a 4 h or a 24 h infusion. In vitro the effect of ADM on clonogenic cell growth was determined after exposure during 5 min, 2 h and 24 h of human bone marrow cells to increasing ADM concentrations. ADM showed rapid intracellular accumulation, to levels 100-fold the plasma concentration in vivo or the incubation medium concentration in the in vitro experiments. After a bolus injection or 5 min exposure only approximately 10% of the cellular peak ADM was retained after elimination of the drug from the plasma or the incubation medium. Ninety percent of the ADM was apparently 'loosely' bound. After 4 h and 24 h constant-rate infusions and also after 2 h and 24 h incubations in vitro, the cells accumulated ADM gradually, and the subsequent washing-out of the cellular ADM was substantially less, most of the ADM being 'tightly' bound. Despite these different patterns of uptake and retention after in vivo short- and long-lasting infusion of the same total dose, the 'tightly-bound' cellular ADM concentrations were the same. Moreover, comparable cellular ADM concentrations, retained after efflux of the 'loosely-bound' cellular ADM fraction were equally cytotoxic to normal human clonogenic cells. Short-lasting cellular peak ADM concentrations which occur after a bolus injection or after short exposure to high ADM concentrations are not essential for the cytotoxic effect, in contrast to the retained, 'tightly-bound' cellular ADM levels.

Bone Marrow↗
PubMed1987

A simple method to obtain low density marrow cells for human marrow transplantation.

Removal of more than 99% of the erythrocytes and 74% of the nucleated cells from marrow grafts was achieved by density floatation separation in Percoll gradients with a density of 1.070 g/ml in eight 250-ml tubes, containing up to 3 X 10(9) nucleated cells per gradient. More than 90% of the myeloid and erythroid progenitor cells were recovered in the low density fraction. It appeared mandatory to use a centrifuge with the possibility of a gradual acceleration and deceleration. Twenty-five patients received a marrow graft from a histocompatible sibling after additional lymphocyte depletion by counterflow centrifugation, and 5 patients with T lymphoblastic malignancies received an autograft after in vitro purging with immunotoxins. All evaluable patients engrafted within normal limits, except 1 patient with an autoimmune pancytopenia who responded to steroids and 1 patient with a CMV infection. Four patients died too early for complete evaluation. The described separation method is easy, cheap and requires only 2 h for the complete processing of a marrow graft.

Bone Marrow Transplantation↗
PubMed1987

Randomized prospective study of ceftazidime versus ceftazidime plus cephalothin in empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime plus cephalothin in 102 febrile neutropenic patients. Thirty bacteriologically documented infections, of which 23 were bacteremias, in 48 clinically assessable patients were treated with ceftazidime alone. Twenty-four bacteriologically proven infections, of which 18 were bacteremias, in 42 clinically assessable patients were treated with a combination of ceftazidime and cephalothin. The clinical response rates in assessable patients were 77% for ceftazidime monotherapy and 88% for the combination. The bacteriological clearance rate was 70% for ceftazidime monotherapy and 79% for the combination. Efficacy against gram-negative pathogens appeared to be excellent, with 93% clearance for ceftazidime monotherapy and 100% clearance for the combination. The bacteriological clearance of gram-positive infections was only 60% for both regimens, with failures mainly due to Streptococcus faecalis and Streptococcus sanguis, which are primarily resistant to both ceftazidime and cephalothin. After addition of vancomycin to those infections which did not respond to empiric therapy, bacteriological clearance rates of 94% (ceftazidime plus vancomycin) and 90% (ceftazidime and cephalothin plus vancomycin) were achieved. Three superinfections were registered in the ceftazidime group and two were seen in the combination group. Other adverse effects of ceftazidime were minimal and were not enhanced by combination with cephalothin. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients, especially if one is prepared to modify therapy if resistant gram-positive strains or mycotic infections are encountered. Neither the clinical nor bacteriological cure rates could be substantially improved by adding cephalothin to ceftazidime in initial empiric treatment of febrile neutropenic patients.

Adolescent↗
PubMed1987

Origin of T-lymphocytes in human mixed hematopoietic colonies.

The presence of T-lymphocytes in mixed hematopoietic colonies (CFU-MIX) has been reported by some investigators. Though depletion before culturing was performed, residual T cells might be responsible for the observed phenomenon. Using nondepleted marrow or bone marrow depleted to about 2%, T-lymphocytes could be detected in mixed colonies. However, reduction of the T-lymphocytes to less than 0.7% by using a modified E-rosette technique or a cocktail of anti-T-cell monoclonal antibodies (WT1, WT32, WT82) in the presence of baby rabbit complement, resulted in mixed colonies free of T-lymphocytes. After addition of 1.75% T-lymphocytes to this T-cell-depleted bone marrow, T-lymphocytes could be detected in most mixed colonies, but not after the addition of the same percentage of irradiated T-lymphocytes. The presence of T cells in mixed colonies was determined by an adapted immunofluorescence technique (WT32 plus GAM-FITC). The results indicate that mononuclear cells with T-lymphocyte antigens are not the offspring of mixed hematopoietic colony-forming progenitors, but of a low number of T-lymphocytes contaminating the bone marrow after insufficient T-cell depletion.

Cytological Techniques↗
PubMed1987

Influence of dose and duration of exposure on the cytotoxic effect of cytarabine toward human hematopoietic clonogenic cells.

The cytotoxic effect of cytarabine (ara-C) on the clonogenic potential of human normal and leukemic hematopoietic cells was investigated. Cells were exposed to ara-C at different concentrations and for periods of one to 120 hours and continuously. Colony growth (CFU-GM/CFU-E/BFU-E) in semisolid culture was assessed after seven and 14 days. The exposure time to ara-C appeared much more important in colony growth inhibition than the drug concentration. For instance, one-hour exposure to 10(-5) mol/L ara-C appeared not cytotoxic, while cocultivation in the presence of 10(-7) mol/L ara-C resulted in a total inhibition of colony growth. Cell fractionation with use of counterflow centrifugation allowed enrichment in subfractions for cells with different amounts of DNA. The inhibition of the clonogenic potential by ara-C was most pronounced in the cell fractions with the highest proliferation activity. Colony-forming cells, assessed after 14 days of culturing appeared less sensitive for ara-C cytotoxicity than seven-day CFUs. This means that ara-C is more cytotoxic to cycling than noncycling cells because compared to the seven-day colonies, 14-day colonies originate from the more resting, more primitive progenitor cells. The cytotoxicity of ara-C to clonogenic cells appears to be related to the proliferating and the cycling state of the progenitor cells and increases with the time of exposure. This phenomenon may be explained by the fact that ara-C is a cycle-specific drug and by the fact that the probability of cells entering the cell cycle is a time-dependent process. The results of this study indicate that development of more effective antileukemic therapy should not aim so much at very high drug levels but rather at prolonged administration of ara-C.

Bone Marrow Cells↗