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Biomedical subjects

C Haanen

Publications and source records attributed to C Haanen.

At least 127 records · Page 7Linked to original sources
PubMed1986

Specific translocation t(1;3) in acute myelomonocytic leukemia: a further case.

We describe herein a translocation, t(1;3)(p36;q21), that was found in the bone marrow of a patient with acute myelomonocytic leukemia preceded by a long lasting myelodysplastic phase. An identical translocation has been reported in three other myelodysplastic patients. one of whom also developed an acute myelomonocytic leukemia. The possible significance of this specific translocation is briefly discussed.

Bone Marrow↗
PubMed1986

Plasma and human leukemic cell pharmacokinetics of oral and intravenous 4-demethoxydaunomycin.

On 3 consecutive days, 4-demethoxydaunomycin (D-DNM) was administered orally (30 mg/m2) as bolus injection and 4- or 24-hour infusion to seven patients with acute leukemia. Cellular (nucleated blood and bone marrow cells) and plasma drug concentrations were studied. After bolus injection, peak plasma D-DNM concentrations were about 50 mg/ml. D-DNM plasma t1/2s were 0.4 +/- 0.3 hours (T1/2 alpha) and 16.4 +/- 4.7 hours (T1/2 beta). D-DNM concentrations in nucleated blood and bone marrow cells were on the same order of magnitude and amounted to more than 400 times the plasma concentration, whereas 4-demethoxydaunomycinol (D-DNMol) concentrations were about 200 times higher. Cellular D-DNM concentrations were maximal at the end of intravenous dosing and at 2 to 4 hours after D-DNM ingestion. D-DNMol concentrations increased more slowly and accumulated on subsequent treatment days in cells and plasma; D-DNM and D-DNMol cellular t1/2 times were 42 and 72 hours, respectively. Antileukemic activity was observed.

Administration, Oral↗
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

A possible role of rifampicin in prolonging remission duration in acute myelogenous leukaemia.

The remission duration (RD) of 22 adult acute myelogenous leukaemia patients who received maintenance rifampicin treatment during 24 episodes was significantly longer than RD in 29 complete remission patients who received conventional maintenance chemotherapy (25 versus 9 months, p less than 0.003). Although this study was not randomized, the observed RD in the rifampicin group suggests a suppressive activity upon regrowth of residual disease in acute myelogenous leukaemia during apparent complete remission.

Clinical Trials as Topic↗
PubMed1986

Factor XI kinetics after plasma exchange in severe factor XI deficiency.

Plasma exchange in a patient with factor XI deficiency allowed the determination of the factor XI disappearance time. The decay curve showed a biphasic pattern with a t1/2 of h. After a loading dose by means of plasma exchange with fresh frozen plasma (FFP) up to a factor XI level of 65%, administration of 0.5 liter FFP every 12 h was necessary to maintain the factor XI concentration between 40 and 60%. The clearances of factor XI, calculated from the results of plasma exchange and from the maintenance dose, correlated very well and showed that the t1/2 of factor XI did not change after surgery. The patient underwent major surgery uneventfully but ultimately died 3 1/2 weeks after operation from cerebral damage due to cardiac arrest, which occurred on the 2nd postoperative day.

Factor XI↗
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

A single-parameter analog level discriminator: a cheap and powerful extension of FCM data acquisition.

Modern flow cytometers offer the possibility to measure more parameters of individual cells than the normally available data acquisition equipment can store. To enlarge the number of parameters that is taken into account while recording data, an analog level discriminator is described that is easy to build and easy to implement on any existing FCM system. An example of gated data acquisition in light scattering measurements on nucleated human bone marrow cells is given. The level discriminator may give a cheap and yet valuable extension of expensive data acquisition equipment.

Electronics↗
PubMed1985

Quantitation of anthracyclines in human hematopoietic cell subpopulations by flow cytometry correlated with high pressure liquid chromatography.

The major white cell subpopulations present in bone marrow and peripheral blood can be discriminated by forward and perpendicular light scatter two-parameter flow cytometry (FCM). Fluorescent properties of anthracycline antibiotics allow measurement of the concentration of these cytotoxic drugs in hematopoietic cells by FCM as a third parameter. Analysis of scatter-gated fluorescence histograms provides quantitative information about the cellular concentration of at least four cell categories in human blood and bone marrow cells. A good correlation was found between the mean cellular fluorescence measured by FCM and the overall cellular concentration of adriamycin, daunomycin, and their main metabolites determined with high-pressure liquid chromatography (HPLC). In incubation experiments with human hematopoietic tissues, the final concentration of various anthracyclines in subpopulations of white cells appeared to be dependent on cell density, incubation time, temperature, and type of compound and its concentration. FCM analysis is a rapid, sensitive, and quantitative method for measurement of cellular anthracycline concentrations in subpopulations and therefore provides an useful new tool in monitoring chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1985

A hereditary abnormal c-fms proto-oncogene in a patient with acute lymphocytic leukaemia and congenital hypothyroidism.

A patient with congenital hypothyroidism and acute lymphocytic leukaemia was found to be homozygous for a 0.4 kbp deletion in the c-fms proto-oncogene. This was established by studying DNA from the patient's leukaemic cells, from cultured skin fibroblasts of the patient and from normal white blood cells of both parents. The uncertain relevance of this finding to the condition of the patient is discussed.

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

Intermittent melphalan in the treatment of essential thrombocytosis with haemorrhage or thrombosis.

178 episodes of essential thrombocytosis with symptoms of haemorrhage or thrombosis, were treated in 15 patients with melphalan (5 mg/m2 orally during 4 d). An average reduction in the platelet count of 77% was achieved by oral melphalan in 14 responding patients. 1 patient appeared to be refractory to oral therapy, but a decrease of the thrombocyte count was achieved after intravenous administration of melphalan. All responding patients experienced a relief of the thrombocytosis-associated clinical symptoms. Reduction of the thrombocyte count persisted for 3-4 wk.

Adolescent↗
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↗