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Biomedical subjects

C Nissen

Publications and source records attributed to C Nissen.

At least 109 records · Page 6Linked to original sources
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

Hemopoietic regulatory factors in human hemopoietic failures.

There are two distinct hemopoietic activities in human serum that do not have the properties of the known hemopoietic lymphokines. These two activities appear not to be produced by immune competent cells. "Direct" stimulatory activity acts in primary target cultures of normal marrow. There does not appear to be a feedback mechanism between bone marrow failure and "direct" activity; it appears to reflect ongoing disease. Indirect "releaser" activity stimulates peripheral blood cells to produce hemopoietic growth factors. It is invariably elevated when release of hemopoietic growth factors is poor, indicating that a feedback mechanism exists. The peripheral blood cells of young patients, particularly young girls, respond poorly to autologous "releaser" stimulation. Results of treatment with ALG in this group are poor. However, all patients with aplastic anemia appear capable of producing adequate amounts "releaser" factor.

Adult↗
PubMed1988

Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia.

Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte-macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.

Adult↗
PubMed1987

A comparison between ALG and bone marrow transplantation in treatment of severe aplastic anemia.

One hundred patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983. 28 patients had a HLA-identical sibling donor and were treated with bone marrow transplantation. 72 patients without a HLA-identical sibling donor were given antilymphocyte globulin followed by oral low dose androgen therapy. One and a half years to nine years after treatment 13 patients (46%) survive in the transplant group and 53 patients (74%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematological complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hemopoiesis: macrocytosis, mild granulocytopenia and mild thrombocytopenia. Relapse (11 of 72 patients) and clonal hematological disorders, such as paroxysmal nocturnal hemoglobinuria (4 patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. In spite of this we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplantation or antilymphocyte globulin.

Anemia, Aplastic↗
PubMed1987

Influence of stored aqueous ceftriaxone solutions on colony formation by neutrophil and macrophage precursor cells.

Aqueous solutions of ceftriaxone in concentrations similar to those achieved in man and stored at temperatures of 4 degrees C, 22 degrees C and 37 degrees C for up to four weeks were tested in methylcellulose cultures of normal bone marrow from ten donors. No significant differences were detected between the colony formation by neutrophil and macrophage precursors in control cultures and in cultures containing stored ceftriaxone. It is concluded that aqueous ceftriaxone solutions stored for up to four weeks at temperatures up to 37 degrees C are not altered to such an extent that they adversely affect colony formation by bone marrow progenitor cells from healthy donors.

Bone Marrow↗
PubMed1987

Engraftment of T-cell-depleted rabbit bone marrow.

T cell depletion of donor bone marrow prevents graft-versus-host disease (GvHD) but increases the risk of rejection. Rabbit bone marrow was T-cell-depleted using the properties of rabbit T cells to form spontaneous rosettes in the cold and by incubation in methylprednisolone (1 mg/ml, 10(6) cells/ml). New Zealand white rabbits were transplanted with Red Burgundy rabbit bone marrow from the opposite sex after conditioning with 12 Gy total body irradiation. Untreated animals die of GvHD at day 23. Three groups were studied: T cell depletion plus ciclosporin (A), T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat (B), and T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat plus ciclosporin (C). Buffy coat cells irradiated with 15 Gy were given for 5 days. Such cells do not form colonies in culture; however, they are able to release interleukin-2. In group A, 9 of 15 animals rejected, 6 survived for 45 days (median, range 16-249 days). In group B, all 5 of 5 animals died of rejection (median survival time 14 days, range 13-20 days). In group C, 8 of 10 animals did engraft, 4 died of GvHD (median survival 48 days, range 26-58 days), and 4 are long-term survivors (greater than 6 months to greater than 1 year), 3 as complete chimeras. We conclude that the combination of irradiated donor buffy coat cells, irradiated autologous bone marrow and ciclosporin restores engraftment of T-cell-depleted mismatched bone marrow without losing the benefit of reduced GvHD.

Animals↗
PubMed1987

[Serum factors and their effect on hematopoiesis].

Human serum contains stimulators of hemopoietic precursor cells. Isolation of "factors" from serum is technically more difficult than from supernatants due to interactions of "factors" with the high molecular weight serum proteins. On the other hand, serum factors are naturally occurring activities which are likely to play a role in regulation of hemopoiesis. Two hemopoietic stimulators which differ from the known colony stimulating factor have been found in human serum. One of them is an indirect "releaser" activity, which induces the release of granulocyte colony stimulating factor (G-CSF) from normal peripheral blood lymphocytes. In patients whose cells release abnormally low amounts of G-CSA, this serum activity is elevated, indicating a feedback mechanism between "releaser" activity and the actual release. G-CSA itself does not circulate in serum. Thus, we assume that releaser activity has a local effect in the bone marrow on the release of G-CSF. These observations suggest that hemopoiesis is regulated by multi-step hormonal mechanisms, in analogy to other known hormone systems.

Anemia, Aplastic↗
PubMed1986

[Adverse effects of total body irradiation for bone marrow transplantation: prevention and therapy. Experience at Basel, July 1979-March 1986].

Acute toxicity, delayed complications and the incidence of interstitial pneumonitis (IP) after total body irradiation (TBI) are reviewed. Between July 1979 and March 1986 118 patients with hematological malignancies underwent bone marrow transplantation (BMT): all were conditioned with cyclophosphamide and TBI. 106 patients received single dose irradiation (18 with lung-shielding) and 12 had fractionated TBI. Except for mucositis all other symptoms of acute toxicity such as fever, vomiting, parotitis, headache and abdominal pain were usually of short duration. Fractionated TBI did not produce less acute side effects than single dose irradiation. Irradiation, and particularly the maximum lung dose, plays an important role in the multifactorial pathogenesis of IP. Delayed complications may appear several months or years after TBI. The majority of men suffer definitive sterility caused by azoospermia. In women primary ovarian failure and permanent sterility is a common sequela of BMT with TBI. The risk of developing cataracts after single dose TBI is about 80%, and surgical repair was necessary in 43% of these cases. Secondary tumors after TBI have been reported. So far we have observed no secondary malignancies in our patients after BMT. Rampant dental decay can be avoided by careful dental prophylaxis.

Adolescent↗
PubMed1986

The release of interleukin-2 (IL-2) and colony stimulating activity (CSA) in aplastic anemia patients: opposite behaviour with improvement of bone marrow function.

Peripheral blood cells from patients with aplastic anemia were tested for their ability to release interleukin-2 (IL-2) and colony stimulating activity (CSA) before treatment. IL-2 release--as measured in the mouse thymocyte assay--was abnormally high in 18/34, and abnormally low in 10/34 patients. "Low" release was due to simultaneous release of thymocyte inhibitors. In 18 patients who achieved self-sustaining hemopoiesis after high dose immunosuppressive therapy, excess IL-2 release decreased to low levels (p less than 0.001), and the release of inhibitors disappeared. In contrast, the release of CSA by patient cells--which did not correlate with peripheral blood monocyte counts--either remained high or increased to excessively high values in 24/24 patients tested before and after successful immunosuppressive treatment. Patients with stable hemopoietic grafts after bone marrow transplantation for aplastic anemia, did not release excess CSA. It is concluded that IL-2 and CSA play opposite roles in aplastic anemia. High IL-2 release seems associated with disease activity, whereas high CSA-release appears to reflect a repair mechanism.

Adolescent↗
PubMed1986

Immunoadsorption for removal of anti-A and anti-B blood group antibodies in ABO-incompatible bone marrow transplantation.

About 10-15 percent of all patients undergoing allogeneic bone marrow transplantation have a major ABO-incompatibility with their donors. The risk of acute hemolytic reactions due to the infusion of an incompatible donor marrow into the recipient can basically be prevented by recipient antibody depletion or by donor marrow red cell depletion. Nine patients were treated by immunoadsorption using a cartridge with chemically synthesized human blood group A and B antigen as immunoadsorbent for antibody depletion. Within a four-hour-procedure about 2-4 times the patient plasma volume could be processed, thus lowering the anti-A and -B hemagglutinins by 2 to 3 tubes. There was a tendency of better IgG removal when titers initially were high, showing a high antibody clearing capacity. There was no significant correlation between starting titer or amount of plasma volume processed and titer reduction. No decrease in titers were observed in one case. We propose repeated immunoadsorption procedures over 2-3 consecutive days before BMT. The procedure is largely safe and without serious side effects. A major advantage is the avoidance of nonautologous human blood products compared to the conventional plasma exchange. All 8 patients surviving long enough had prompt and stable engraftment of all three cell lines post BMT. No late serological complications occurred when patients were regularly monitored and in vivo adsorption was used when titers increased.

ABO Blood-Group System↗
PubMed1986

Characteristics and clinical relevance of autolymphocytotoxins in patients with aplastic anemia.

Serum of 68 patients with aplastic anemia was tested for the presence of autolymphocytotoxins (auto-LTs). Prior to specific disease treatment, 16 patients (24%) displayed antibodies cytotoxic to their own lymphocytes. These antibodies had the characteristics of cold-reactive lymphocytotoxins. Their detection in patients' sera was found unrelated to a viral or toxic cause of the disease or the patients' HLA genotype. Broadly reactive anti-HLA antibodies were less frequent in pretreatment sera containing auto-LTs, suggesting that these autoantibodies could modulate alloantibody production. However, after specific disease treatment, the alloantibody frequency was comparable in patients with or without auto-LTs. We found no significant difference in response to antilymphocyte serum or bone marrow graft outcome in the patients in relation to the presence or absence of pretreatment auto-LTs. This observation suggests that the detection of these autoantibodies in aplastic anemia has no clinical relevance.

Adolescent↗
PubMed1986

Influence of graft-versus-host disease prophylaxis on early T-lymphocyte regeneration following allogeneic bone marrow transplantation.

An early decrease in the ratio between T4+ and T8+ T lymphocytes has been shown to correlate with the development of grade II-IV GVHD in allogeneic bone marrow transplant (BMT) recipients receiving methotrexate (MTX) as prophylaxis for acute graft-versus-host disease (GVHD). This study compares the onset of T-cell regeneration in patients receiving cyclosporin A (CyA) with those receiving MTX. Firstly, lymphoid recovery occurred at a significantly faster rate in the patients on CyA. Secondly, in those patients, the repopulation of T4+ and T8+ T cells started simultaneously, whereas in patients on MTX the repopulation of the T8+ subset lagged about a week behind that of the T4+ subset. Thirdly, the decrease in the T4/T8 ratios as a function of the lymphocyte counts occurred at a significantly slower rate in the patients on CyA than in those on MTX. Thus, the differences in the onset of T-cell regeneration in BMT recipients on CyA as compared with those on MTX abolished the correlation of the T4/T8 ratio changes with grades II-IV GVHD as described in patients receiving MTX.

Adolescent↗
PubMed1986

Acquired aplastic anaemia: a PNH-like disease?

Bone marrow from 20 patients with aplastic anaemia at different stages of disease and from three patients with paroxysmal nocturnal haemoglobinuria (PNH) was incubated in isosmolar sucrose with 5% autologous serum prior to culture in methylcellulose. If fresh serum was used, colony formation by granulocyte-macrophage colony forming cells (GM-CFC) and immature erythroid precursors (BFU-E) was reduced to approximately 50% in all patients tested, at any stage of disease, including complete autologous bone marrow recovery. Heat inactivation and complement inactivation with EDTA completely abrogated this inhibitory serum effect. Selective inactivation of the classical, antibody dependent complement pathway with Mg2+ EGTA reduced the inhibitory effect by 50%. Complement sensitivity of haemopoietic precursors is a known feature of PNH. Since the majority of our patients did not have PNH as judged by a negative sucrose-test on mature erythrocytes, we conclude that, in aplastic anaemia, haemopoietic cells express a PNH-like defect at a primitive level.

Anemia, Aplastic↗