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Biomedical subjects

T de Witte

Publications and source records attributed to T de Witte.

At least 145 records · Page 8Linked to original sources
PubMed1986

Ceftazidime does not enhance cyclosporin-A nephrotoxicity in febrile bone marrow transplantation patients.

Ceftazidime was used as monotherapy for 30 febrile episodes in 28 patients, who underwent allogeneic bone marrow transplantation and who were treated concomitantly with the immunosuppressive agent cyclosporin-A. Ceftazidime did not enhance the well established nephrotoxicity of cyclosporin-A as measured by serum creatinine levels or creatinine clearance. Although an increasing number of Gram-positive infections in these patients warrants vigilance, ceftazidime as initial empirical monotherapy proved to be successful in 95% of all febrile post-transplantation patients. All Gram-negative and 69% of the Gram-positive infections were cured with ceftazidime alone. The overall clinical cure rate was 72%, with microbiological clearance in 63%. This compares favourably with aminoglycoside containing schedules and avoids the aminoglycoside associated nephrotoxicity.

Adult↗
PubMed1986

Remission-induction of acute lymphoblastic transformation of chronic myeloid leukaemia, followed by long-term maintenance therapy.

Acute lymphoblastic transformation of chronic myeloid leukaemia (LT-CML) of 7 consecutive patients was treated according to a remission-induction and maintenance therapy used for de novo acute lymphoblastic leukaemia (ALL). All 7 patients achieved a second chronic phase with a median remission duration of 15 months. Two patients showed an isolated central nervous system (CNS) relapse. This did not occur in the 4 patients, who received prophylactic therapy with intrathecal methotrexate. The second transformation was nonlymphoblastic in nature in 4 out of the 5 patients. A treatment protocol similar to that of a bad risk ALL, including long-term maintenance therapy and CNS-prophylaxis is indicated in lymphoblastic transformation of CML.

Adult↗
PubMed1986

Ceftazidime alone for treating Pseudomonas aeruginosa septicaemia in neutropenic patients.

Twenty-nine patients with primary or secondary hypoplastic bone-marrow were treated successfully with ceftazidime alone for established septicaemia caused by Pseudomonas aeruginosa of which 38% strains were gentamicin-resistant . All the patients were neutropenic at the start of therapy; most were cured with microbiological confirmation before the bone marrow had regenerated. One patient died of cerebral haemorrhage due to profound thrombocytopenia without evidence of infection at autopsy. Significant toxicity was not observed. Ceftazidime alone is, therefore, a safe and effective treatment for infections caused by this organism even in the neutropenic patient.

Agranulocytosis↗
PubMed1986

The relation of exposure time and drug concentration in their effect on cloning efficiency after incubation of human bone marrow with cytosine arabinoside.

The effect of different cytosine arabinoside (Ara-C) concentrations and exposure times upon clonogenicity of normal bone marrow cells was studied. One hour incubation, even at the pharmacologically high Ara-C concentration of 10(-5) M, was not cytotoxic. Prolonged incubation resulted in a very great increase in Ara-C cytotoxicity, provided that inactivation of Ara-C by deamination was limited. The results show that long-term exposure to Ara-C, even at pharmacologically very low concentrations, is deleterious to clonogenic cells and provide an experimental basis for the reported therapeutic efficacy of long-term low dose Ara-C administration in leukaemia and preleukaemic syndromes.

Bone Marrow↗
PubMed1986

Enrichment of human bone marrow aspirates for low-density mononuclear cells using a haemonetics discontinuous blood cell separator.

Isopycnic density floatation centrifugation has been proven to be a suitable technique to enrich bone marrow aspirates for clonogenic cells on a small scale. We have tested a Haemonetics semicontinuous blood cell separator in order to process large volumes of bone marrow with minimal bone marrow manipulation. The efficacy of isopycnic density floatation was tested in a one and a two-step procedure. Both procedures showed a recovery of about 20% of the nucleated cells and 1-2% of the erythrocytes. The enrichment of clonogenic cells in the one-step procedure appeared superior to the two-step enrichment, first separating buffy coat cells. The recovery of clonogenic cells was 70 and 50%, respectively. Repopulation capacity of the low-density cell fraction containing the clonogenic cells was excellent after autologous reinfusion (6 cases) and allogeneic bone marrow transplantation (3 cases). Fast enrichment of large volumes of bone marrow aspirates with low-density cells containing the clonogenic cells by isopycnic density floatation centrifugation can be done safely using a Haemonetics blood cell separator.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Monitoring of cyclosporin during continuous intravenous administration.

Intravenous cyclosporin was administered continuously to 18 consecutive marrow transplant recipients. Blood samples taken from the single lumen central venous line through which the cyclosporin was administered showed invariably high concentrations. Toxic levels were still present after discontinuation of cyclosporin administration for 8 h, while the peripheral blood levels were in the therapeutic range throughout the observation time. These observations may explain some of the reported discrepancies between the levels of cyclosporin and the side-effects when using intravenous cyclosporin. Mean cyclosporin levels remained stable throughout the 4 weeks of continuous intravenous cyclosporin administration, despite a gradual decrease of the mean cyclosporin dose. Dose adaptations were made based on clinical side-effects and cyclosporin concentrations in blood samples from peripheral veins.

Adolescent↗
PubMed1986

Depletion of donor lymphocytes by counterflow centrifugation successfully prevents acute graft-versus-host disease in matched allogeneic marrow transplantation.

Bone marrow from 22 histocompatible siblings was depleted of 98% of the lymphocytes using a combination of density flotation centrifugation followed by counterflow elutriation. Even with the marrow suppressive influence of methotrexate (MTX), the viability of the hematopoietic stem cells was not affected, as indicated by the normal repopulation after grafting in the evaluable patients. One patient (UPN 9) showed a primary graft failure, possibly resulting from persisting septicemia and long-term antibiotic therapy. Two patients have persistent host lymphocytes, one of whom was examined during relapse; the other remains in remission. Two patients did not receive immunosuppression after bone marrow transplantation (BMT), and acute graft-v-host disease (GVHD) developed in both. Nine patients received MTX as immunosuppression following BMT. GVHD did not develop in any of them, but fatal infections in the immediate posttransplant period developed in five patients. Eleven patients received cyclosporine (CsA) after transplantation. Beginning in week 5 after BMT, CsA was gradually replaced by MTX. Acute GVHD, substantial chronic GVHD, or fatal infections did not develop in any of these patients. Removal of 98% of the lymphocytes by counterflow centrifugation prevents development of acute GVHD, provided that immunosuppression is administered after BMT. Graft rejection was not observed, but the number of evaluable patients is limited at present.

Adolescent↗
PubMed1985

Concentration of hematopoietic progenitor cells from human bone marrow by a new type of blood component separator.

A new type of blood component separator (BCS) was used for the isolation of hematopoietic progenitor cells from human bone marrow aspirates. The BCS was filled with 100-150 ml bone marrow and centrifuged to prepare a buffy coat. This buffy coat was isolated in 10-15% of the original bone marrow volume and contained 64 +/- 8% of the nucleated cells (NC). Morphological examination revealed that the buffy coat was highly enriched for myeloblasts, promyelocytes, lymphocytes and monocytes, whereas the contamination with granulocytes was reduced to 46 +/- 8% of the granulocytes initially present in the bone marrow suspension. In addition the contamination with red blood cells (RBC) was very low; the buffy coat contained only 6 +/- 2% of the RBC. Furthermore it was demonstrated by means of colony assays that the buffy coat was highly enriched for hematopoietic progenitor cells. It contained 91 +/- 6% of the granulocyte/monocyte progenitor cells (CFU-GM) and 87 +/- 9% of the erythroid progenitor cells (BFU-E). These results are comparable to those obtained with continuous or semicontinuous blood cell processors. The advantages of the BCS is that it is a simple and inexpensive apparatus which fits in a normal blood bank centrifuge. It permits efficient preparation and isolation of a buffy coat from human bone marrow without substantial loss of hematopoietic progenitor cells.

Bone Marrow Cells↗
PubMed1985

Repetitive cycles of cytoreductive therapy followed by stem cell autografting for nonlymphoblastic transformation of chronic granulocytic leukaemia.

Treatment of nonlymphoblastic transformation of chronic granulocytic leukaemia (CGL) by marrow ablative chemotherapy, followed by autologous stem cell reinfusion, induced a 2nd chronic phase with a median duration of 5.5 months at the cost of high morbidity and mortality. One course of intensive cytoreductive chemotherapy, similar to a remission induction course in acute nonlymphoblastic leukaemia (ANLL), followed by a buffy coat reinfusion, induced a short-lived 2nd chronic phase in 4 out of 9 patients. Two successive courses, each followed by an autologous stem cell reinfusion, induced a new chronic phase in 4 out of 5 consecutive patients. Multiple intensive chemotherapy courses, followed by autologous stem cell rescue, offer an effective palliative treatment of nonlymphoblastic transformation of CGL with a relatively low morbidity due to the treatment itself.

Adult↗
PubMed1985

A randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective, randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime and flucloxacillin in 100 febrile neutropenic patients. Thirty-four bacteriologically documented infections, of which 26 were bacteremias, in 51 patients were treated with ceftazidime alone. Thirty-four bacteriologically proven infections, of which 29 were bacteremias, in 49 patients were treated with a combination of ceftazidime and flucloxacillin. The clinical response rate for ceftazidime monotherapy was 80%; the bacteriological cure rate was 90%. Efficacy against gram-negative pathogens appeared to be excellent, achieving a 100% cure rate. The clinical response and bacteriological cure rates for the combination were 76 and 86%, respectively. Three superinfections were registered in the ceftazidime group, and four, involving six pathogens, were registered in the combination group. Other side effects of ceftazidime were minimal. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients. It offers the opportunity to avoid the aminoglycosides in first-line treatment. It may be appropriate to combine ceftazidime with cephalothin or vancomycin or to modify therapy if resistant gram-positive strains are encountered.

Adult↗
PubMed1985

Influence of peripheral blood admixture on the number of hematopoietic progenitor cells (CFU-GM and BFU-E) in human bone marrow aspirates.

Peripheral blood contamination in human bone marrow aspirates was calculated from the ratios between the erythrocyte and nucleated cell counts in both the bone marrow aspirate and a simultaneously obtained peripheral blood sample. This method is based upon experimental data which showed that the erythrocytes in bone marrow aspirates are mainly derived from the intravascular blood compartment. A strong negative correlation was found between the peripheral nucleated cell fraction (FBl) and the number of myeloid progenitor cells in 65 bone marrow samples (correlation coefficient r = -0.51; p less than 0.001). A similar correlation was found between erythroid progenitor cells and peripheral blood fraction (r = -0.55; p less than 0.01). The culture conditions were continuously monitored, using large batches of frozen marrow samples as controls. The correction for peripheral blood admixture permits a more reliable and reproducible interpretation of the quantitative results obtained from studies on the number of clonogenic cells in human bone marrow aspirates. Moreover, the method allows the interpretation of data obtained from bone marrow samples which are heavily contaminated by peripheral blood.

Biopsy, Needle↗
PubMed1984

Allogeneic bone marrow transplantation in a patient with acute myeloid leukemia secondary to Hodgkin's disease.

A patient with Hodgkin's disease entered complete clinical remission by combination radiochemotherapy. He developed dyshematopoiesis 1.5 years later and an overt acute nonlymphocytic leukemia 3 years after diagnosis. A complete remission was achieved following 2 courses of intensive polychemotherapy. Four months later, while still in remission, he underwent an allogeneic bone marrow transplantation (BMT) from an HLA-identical sister. Mild chronic graft versus host disease of the skin occurred 3 months after BMT, and now the patient has been in complete remission of leukemia for over 2 years. This appears to be a unique case of prolonged remission of a leukemia secondary to an intensively treated Hodgkin's disease.

Acute Disease↗
PubMed1984

Separation of immunoreactive lymphocytes from human pluripotent stem cells (CFU-GEMM) by means of counterflow centrifugation.

Counterflow centrifugation with continuous monitoring of the output for cell number and cell scatter was used to separate low density (d less than 1.070 g/ml) human bone marrow cells in two fractions: one containing the majority of small size lymphocytes and the other the majority of the larger sized committed progenitor cells. The recovery of the pluripotent stem cells (CFU-GEMM) in the large cell fraction was complete. The mitogenic reactivity of this putative stem cell fraction had decreased to 6% and 11%, of the original value as measured with phytohemagglutinin stimulation and one way mixed lymphocytic culture respectively. Counterflow centrifugation offers a physical separation technique, by which the majority of the immunoreactive cells can be separated from the pluripotent hematopoietic stem cells.

Bone Marrow Cells↗
PubMed1984

Bone marrow repopulation capacity after transplantation of lymphocyte-depleted allogeneic bone marrow using counterflow centrifugation.

Bone marrow from six allogeneic HLA-matched and MCL nonreactive siblings was fractionated by means of isopycnic flotation centrifugation and subsequent counterflow centrifugation. The low density fraction (d less than or equal to 1.070 g/ml) obtained by IFC contained 20% of the nucleated cells and more than 90% of the myeloid and erythroid progenitors. The putative stem cell fraction obtained by CC showed a satisfactory recovery (88%) of the CFU-GM and BFU-E and only 3.5% of the original number of T lymphocytes. Bone marrow repopulation capacity was not impaired in comparison with a comparable group of patients. Despite the average high age of this group (29.6 years), only one of the four evaluable patients developed graft-versus-host disease.

Adolescent↗
PubMed1984

Separation of human bone marrow by counterflow centrifugation monitored by DNA-flowcytometry.

Human bone marrow was fractionated by counterflow centrifugation into 16 fractions with increasing cell size. Three distinct subpopulations could be recognized: small lymphocytic cells, medium-sized nucleated erythroid cells and large myeloid elements. DNA-flowcytometry and 3H-thymidine uptake showed that within the erythroid and myeloid cell populations counterflow centrifugation separates each population according to the cell cycle phase. Hypotonic treatment of bone marrow for removal of the erythroid nucleated cells resulted in a complete abrogation of the proliferating erythroid cell population. Counterflow centrifugation also separates the small non-proliferating myeloid and erythroid committed stem cells from the larger proliferating stem cells. It appeared feasible to separate the small lymphocytic cells from the majority of BFU-E and CFU-GM, due to the larger size of the proliferating normoblasts and the committed progenitor cells. Elimination of the mature lymphocytes from the haematopoietic stem cells by counterflow centrifugation may offer an alternative approach to the prevention of graft versus host disease (GvHD).

Bone Marrow↗
PubMed1984

T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease.

Acute graft-versus-host disease (GVHD), a major complication of allogeneic bone marrow transplantation (BMT), is probably mediated by T lymphocytes present in the marrow graft. In this study, the repopulation of the peripheral blood with T4+ and T8+ T cells was investigated during the period preceding the occurrence of acute GVHD. Twenty-four allogeneic and 11 autologous BMT recipients were monitored from day 4 post-BMT onward by the use of monoclonal antibodies, indirect immunofluorescence, and flow cytometry. The recipients of allogeneic transplants received methotrexate as GVHD prophylaxis. Similar recovery patterns for T4+ and T8+ T cells were found following autologous and allogeneic BMT. However, lymphoid repopulation occurred at a clearly faster rate after autologous BMT. T4+ T cells were the first to reappear in the peripheral blood, followed by T8+ T cells 4-7 days later. The T8+ T cell reconstitution occurred at an even faster rate in patients who were to develop grade II-IV GVHD, as compared with those with grade O-I GVHD, thus leading to an earlier decrease in the T4/T8 ratio. Of 10 patients with a T4/T8 ratio less than 2.5 at day 19, 9 developed grade II-IV GVHD and 1 showed no GVHD. Of 14 patients with a ratio greater than 2.5 at that time, only 2 developed grade II-IV and 12 grade O-I GVHD (p less than 0.001). In the 11 patients developing grade II-IV GVHD, the T4/T8 ratio decreased to values less than 2.5 before the first clinical symptoms of GVHD in 9; it coincided in one and occurred later in another patient. Thus, early monitoring of the T4/T8 ratio can distinguish patients at risk of developing grade II-IV GVHD.

Adolescent↗