Search PubMed⌕ Search

Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 343 records · Page 19Linked to original sources

Cyclosporine resistant effector cells in rabbit skin allografts.

Histoincompatible skin grafts in rabbits treated with cyclosporine can permanently engraft but show a transient mononuclear cellular infiltrate. This transient cyclosporine-resistant infiltrate consists of cells which are sensitive to steroids, radiation and cryopreservation. They have the same ACM-1 phenotype and the same characteristics as cyclosporine-sensitive cells.

Animals↗

[Experience using bone marrow transplantation in the treatment of hematologic neoplasms and solid tumors].

Between October 1983 and October 1985, 12 allogeneic bone marrow transplantations from HLA-identical siblings were performed for treatment of malignant disease (11 haemopoietic malignancies) or severe aplastic anaemia (1 case). All patients showed prompt and complete engraftment of donor cells on average around day 17 after transplantation. 10 patients are alive and well 50-760 days after transplantation, without any signs of recurrence and partly without immunosuppressive therapy. Two patients died, one due to relapse of the leukaemia, and one as a result of CMV interstitial pneumonia. Graft versus host disease was seen in 6 of the 12 patients. Additional immunosuppressive therapy was necessary in 4 of them. The incidence of idiopathic interstitial pneumonia in our group of patients was low (two cases). Also tested was an experimental protocol for the treatment of chemotherapy-resistant metastatic solid tumours. After removal of all clinically detectable tumour tissue by maximal surgical therapy in 5 patients, residual systemic metastases were treated by means of total body irradiation and high-dose cyclophosphamide, followed by autologous bone marrow transplantation with curative intention. Relapse occurred in 4 patients between day 100 and 720 after BMT bone marrow transplantation. Only one patient remains without sign of relapse.

Adult↗

Long-term results of two Swiss AML studies.

The Swiss group for clinical cancer research (SAKK) completed two first line protocols for the treatment of acute myelogenous leukemia (AML). In the first protocol (SAKK AML 74, from August 1974 to April 1977; 107 patients) the effectiveness of immunization with viral oncolysate during maintenance treatment was tested. After successful induction treatment, the patients were randomized in two groups: Group A: monthly maintenance chemotherapy for 2 years and group A+IT, which received the same maintenance chemotherapy regimen plus, on day 15, injection of viral oncolysate. Of the 107 patients, 57 (53%) achieved complete remission, 29 then being randomized to group A, 28 to group A+IT. As of August 1984, there is no statistical difference between the survival times of the two groups (p = 0.288). Ten years after the start of the study there is still no clear plateau of the survival curve. Nine percent of all patients (18% of the remission patients) are alive today. With the treatment of the mid-seventies, therefore, the cure of a patient suffering from AML was a rare event. The second protocol (SAKK AML 77, from April 1977 to April 1982; 162 patients) was designed to evaluate the usefulness of a prolonged maintenance treatment after early consolidation. The 74 patients who were still in remission after early consolidation treatment were assigned to either maintenance chemotherapy or to observation only. At 3.5 years after the last patient's entry there was no difference between the groups in duration of survival (p = 0.332).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

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↗

Bone marrow transplantation in multiple myeloma: report from the European Cooperative Group for Bone Marrow Transplantation.

Of 14 patients who received an allogeneic bone marrow graft from HLA-compatible sibling donors, 10 have survived for 6 to 34 months posttransplantation (median, 12 months). Four patients have died, two of relapse at extramedullary sites, one of severe acute GVHD, and one from GI bleeding and pericardial effusion. One patient is alive in relapse and four patients have signs of minimal persistent disease. Five patients are well without signs of active disease. Minor improvement in osteolytic lesions on X-ray were seen in three patients, but the X-ray bone structure was mainly unchanged in most patients. Bone marrow transplantation appears promising for treatment of certain patients with multiple myeloma.

Adult↗

[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↗