[High-dose autologous stem cell administration in malignant diseases--an established method, unclear indications].
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Biomedical subjects
Publications and source records attributed to L Brinch.
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A patient with sideroblastic anemia was splenectomized. After the splenectomy numerous inclusions were present in the erythrocytes, whereas there were almost none before the splenectomy.
Infusion of haematopoietic stem cells, either autologous or allogeneic, allows treatment of malignant diseases with marrow ablative doses of cytostatics or whole body irradiation. Hospitalization and general anaesthesia is necessary for bone marrow harvesting, while the harvest of peripheral stem cells may be performed without hospitalization. Mobilization of haematopoietic stem cells from the bone marrow to peripheral blood, followed by cytapheresis and harvesting of the stem-cell containing fraction is a promising alternative to the harvest of marrow. We have tried this in one patient with advanced acute myeloid leukaemia and discuss our experience and that of others.
We report 11 years experience with a modified version of a chemotherapy programme in use at the MRC Leukaemia Unit from 1982 to 1984, supplemented by allogeneic bone marrow transplantation in first relapse or second or later remission from 1985. 79 consecutive patients aged 15-60 years with newly diagnosed acute lymphoblastic leukaemia (ALL) were given induction chemotherapy. This included a standard DAT course (daunorubicin, cytarabine and thioguanine) applied as in acute myelogenous leukaemia approximately midway in the induction programme. A 3-year rotating maintenance programme consisted of combinations of cytotoxic drugs used in the induction therapy. CNS prophylaxis did not include CNS irradiation. Allogeneic BMT was not performed in first remission. The overall complete remission (CR) rate was 82% (65/79). 26 patients relapsed (seven first in the CNS). Seven patients underwent allogeneic BMT of whom six are alive and well with a mean observation time of 32 months (range 4-99 months) after transplantation. Three patients died in first CR. Estimated 5- and 8-year overall survival was 51% (95% confidence interval (CI) 39-63) and 47% (CI 33-61). For patients who reached CR, the corresponding figures were 63% (CI 50-76) and 57% (CI 41-73). Estimated disease-free survival in the remitters was 54% (CI 40-68) at 5 years and 44% (CI 28-60) at 8 years. Patient age below 25 years and white cell count below 15 x 10(9)/l at presentation were both found to improve the chance of overall survival.
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We present updated results from allogeneic bone marrow transplantation in adult patients who received transplants between 1985 and 1992. Of 47 patients, 36 where disease-free survivors 8-93, mean 32 months after transplantation. Of these, seven had received marrow from unrelated donors. The present treatment capacity is insufficient to cover the demand for allogeneic bone marrow transplants for Norwegian patients.
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Examples of patients are used as a basis for discussing the treatment of severe aplastic anaemia with clonal chromosomal aberrations in haematopoietic cells, the aplastic form of paroxysmal nocturnal haemoglobinuria and myelodysplasia, with allogeneic bone marrow transplantation. Transplantation with marrow from an HLA-identical sibling donor has curative potential in selected patients with these disorders. The procedure should preferably be carried out before the patients have received massive treatment for the complications of marrow failure. The use of matched unrelated bone marrow donors is still at the investigation stage.
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Two patients with relapsed hyper-granular promyelocytic leukemia were treated with all-trans-retinoic acid. Both obtained complete remission with minimal transfusion requirements, no haemorrhagic complications or serious infections, and involving short periods of hospitalization. This course of events corresponds well with previously published information from larger patient materials, which are also discussed in the article.
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Ninety-one patients with acute myelogenous leukaemia (AML) aged 17-59 years were treated with a chemotherapy programme which could be completed within 30 weeks for patients who achieved complete remission (CR). Four courses included daunorubicin, cytarabine and thioguanine, while two courses included amsacrine, etoposide and cytarabine. Sixty-five patients obtained CR (71%), more often in patients below (82%) than above (60%) 40 years of age (P = 0.03). Five patients underwent allogenic bone-marrow transplantation, and one patient received an autologous bone-marrow transplant after relapse. Five patients developed central nervous system leukaemia. The overall actuarial 3- and 5-year survival was 29% and 21%, respectively; for patients who obtained CR the corresponding survival rates were 40% and 30%, respectively. Patients below 40 years of age appeared to fare better (5-year survival 26%) than older patients (5-year survival 16%). The estimated disease-free survival rate was 26% at 3 years and 22% at 5 years. The main advantage of this regimen is that results compare favourably with those obtained with other regimens were achieved, without exposing patients to long periods of maintenance therapy.
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