Allogeneic BMT for AML in Zagreb.
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Biomedical subjects
Publications and source records attributed to D Nemet.
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This first part of the review deals with fundamental knowledge, rationale and methods for the use of autologous bone marrow transplantation in the treatment of neoplastic diseases. Use of high-dose chemo- and radiotherapy in the treatment of neoplastic diseases is limited by side effects on haemopoietic tissues. Bone marrow transplantation offers a possibility to escalate the dose of cytotoxic therapy, but this possibility is limited by two main factors: need for matched allogeneic donor, and patient age below 45 years. This has led to application of autologous BMT for the treatment of older patients and those without compatible marrow donors. Samples of bone marrow collected before intensive myeloablative treatment are stored by means of cryopreservation. Viability and clonogenicity of stored bone marrow stem cells prior to reinfusion into the patient are tested by in vitro bone marrow culture (usually CFU-GM). Treatment of marrow samples in vitro by monoclonal antibodies and/or cytotoxic drugs are used in order to cleane ("purge") the marrow of residual neoplastic cells.
A clinical, light microscope and electron microscope study of skin changes was undertaken in 19 patients after bone marrow transplantation. Thirteen of the total number of 19 patients were clinically suspect of the acute and 6 of the chronic form of GvHD. Skin biopsy between the seventh and thirtieth day following transplantation confirmed the diagnosis of the acute form of GvHD in 7 of the 19 patients. In 4 of the 6 patients in whom skin biopsy did not verify the diagnosis of the acute form of GvHD, completely atypical rash in addition to signs of GvHD of the liver and intestines developed between the 30th and 50th day following transplantation. In all 6 patients who were clinically suspect of the chronic form of GvHD, skin biopsy performed some 4-10 months after transplantation confirmed the diagnosis of chronic, sclerodermoid or lichenoid GvHD. Furthermore in 71% of the patients with histologically verified chronic form of skin GvHD, symptoms of liver and intestine GvHD were present too at the time of the skin biopsy. With regard to the fact that histologically the least reliable seems to be the diagnosis of Grade 1 cutaneous GvHD, the authors recommend that regular dermatological follow-up examinations be made in the period of 7 to 50 days following transplantation in addition to skin biopsy in the case of appearance of any rash. Electron microscopy revealed in both forms of GvHD, the acute and the chronic, the most significant epidermal changes, i.e. degeneration of the cellular organelles and the appearance of numerous intracytoplasmic vacuoles.
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In this second part of the review the clinical significance of autologous bone marrow transplantation (ABMT) as treatment for acute leukemias (AL) and malignant lymphomas is described. In most adult patients with AL in complete remission treated with conventional maintenance therapy relapse usually occurs within one year. However, the results of ABMT, as an intensive consolidation treatment in patients with AL in remission show long-term disease-free survival in a proportion of 40% of patients. Even better results have been reported in patients with purged bone marrow, although the difference is not statistically significant. A major problem of ABMT is still the high percentage of relapse (50%), while the probability of treatment related mortality is relatively low (up to 10%). ABMT is also showing good results in the treatment of non-Hodgkin's lymphomas of intermediate and high-grade histology and in Hodgkin's disease in cases refractory to the first line therapy and in sensitive relapse. However, in refractory cases the results are poor. It is noteworthy, that in all disorders treated with ABMT, prospective randomised controlled trials are missing and current data are based on heterogenous groups of patients. In the majority of solid tumors, even escalated doses of radiochemotherapy with ABMT are not able to eradicate malignant disease. In contrast, the results are very good in neuroblastoma. Although ABMT is a relatively complex and aggressive method, it is being increasingly applied to the treatment of haematological malignant diseases and the results obtained so far, are encouraging and showing that ABMT, besides allogeneic BMT, represents a promising potentially curative treatment for selected group of patients.
Autologous bone marrow transplantation (ABMT) allows application of intensive myeloablative therapy aimed at eradication of neoplastic disease by facilitating haematopoietic reconstitution. Between March and June 1988, four patients (two with acute myelogenous leukaemia in first remission, one with acute lymphoblastic leukaemia in second remission, and one with Burkitt lymphoma, stage IV with CNS involvement in second remission) received this treatment. Methods of collecting, processing and freezing bone marrow as well as thawing and reinfusion of the marrow into patients after intensive chemoradiotherapy are described. Viability of bone marrow cells tested by the dye exclusion method after freezing and thawing process was 89, 88, 91 and 78%, respectively. CFU-GM recovery in culture, as a test of marrow stem cells clonogenicity was between 63,3 and 156,5%. Patients received between 1,7 and 3,0 x 10(8)/kg nucleated cells and 4,0 to 7,6 x 10(4)/kg CFU-GM, respectively. In all four patients stable haematopoietic reconstitution was achieved. The bone marrow function was evident mainly at 11th day after marrow reinfusion. Leukocyte count reached 1,0 x 10(0)/L in 11 to 15 days, and granulocyte count raised more than 0,5 x 10(9)/L in 19 to 37 days after transplantation. Platelet recovery was prolonged with the minimum of 29 days and maximum of more than 60 days to reach 20 x 10(9)/L. Side effects caused by the intensive radiochemotherapy were moderate. Bacterial, fungal and viral infections in early posttransplant period were successfully treated. All patients have survived and left the hospital 63, 54, 36 and 65 days after ABMT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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