[The biological characteristics and treatment of acute promyelocytic leukemia].
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Biomedical subjects
Publications and source records attributed to V G Savchenko.
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AIM: To evaluate efficacy of ampicilline/sulbactame and fluconasole in the regimen of empirical antibiotic therapy in patients with acute leukemia. MATERIALS AND METHODS: The trial covered 14 hematological departments of Russia and 1 of Ukraine. Acute myeloid leukemia patients were included. 92 cases of fever in 56 patients with analysis of efficacy in 66 cases were considered. At the first stage of empirical antibiotic therapy, cefoperason (4 g/day) and gentamycin (240 mg/day) were administered. If no response was reached, ampicilline/sulbactam (7.5 g/day) was added. This was the second stage. If no response occurred for 5 days the three drugs were joined by fluconasol (400 mg followed by 200 mg). RESULTS: Fever of unclear genesis was cured in 82% (28 of 34), clinical infection--in 80% (20 of 25), microbiologically confirmed infection--in 4 of 7 cases. A complete response to the empirical antibiotic therapy was registered in 52 of 66 cases (79%). 7(10.5%) patients died of infectious complications. 7(10.5%) received other antibiotics.
AIM: The study of changes in functional activity of albumin ligand centers in the course of accumulation of metabolic products in the blood of hematological patients. MATERIALS AND METHODS: Blood serum albumin transport function (TF) was investigated in 22 and 24 patients with acute and chronic leukemia, respectively. Lipid analyser AKL-01 and the kit "Zond-Albumin" ("Zond", Moscow) were employed to assess total albumin concentration (TAC), effective albumin concentration (EAC), albumin binding reserve (ABR), the toxicity index (TI). The control group consisted of 38 blood donors. The findings were processed with statistical techniques. RESULTS: In patients with manifest acute leukemia, ABR and TI decreased while TAC remained unchanged. Chronic leukemia patients had high EAC and close to control levels of ABR and TI. In terminal chronic leukemia ABR lowered, TI increased, TAC was high but EAC fell. In patients with chronic leukemia and acute leukemia remission changes in albumin TF was accompanied with growing TAC. CONCLUSION: A decline of albumin TF was found in patients with manifest acute leukemia and terminal chronic leukemia. In non-terminal chronic leukemia and in remission of acute leukemia albumin TF was normal.
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Erythrocyte chimerism, graft versus host reaction, and course of disease were studied in patients subjected to bone marrow transplantation from 40 HLA identical sibs and 7 monozygotic twins. Disease relapses were observed in 35% of patients after allogenic and much more often in those after isogenic bone marrow transplantation. Relapses occurred in all patients subjected to transplantation from monozygotic twins. These results may be explained by the genetic and biological deficiencies of bone marrow cells from HLA identical sibs. 15% of recipients developed an acute graft versus host reaction after transplantation from HLA identical sibs; this is three times less than after transplantation from genetically unrelated donors, as reported elsewhere.
To establish the type of hemopoiesis in 15 patients with hemoblastosis subjected to allogenic bone marrow transplantation, the amplification of four hypervariable human genome loci containing tandem repeats with varying copy numbers (loci ApoB, DX, S52, VWF, and YNZ22) were studied by means of polymerase chain reaction. The sensitivity determined by amplification of DNA mixture in dilutions was 1-2%. Based on the data obtained, various types of hemopoiesis recovery after bone marrow transplantation were determined; in most cases, a complete donor chimerism was revealed; in some patients, mixed chimerism; and in one case, a host type of hemopoiesis was found. An association between hemopoiesis type and further development of the disease was observed.
Made in Russia antilymphocytic globulin (ALG) was given to 43 patients with aplastic anemia (AA). 56% of the patients responded, 30% reached a complete or partial remission. 5-year actuarial survival of ALG-treated patients was 52% (44 and 60% for severe and non-severe forms). The data on ALG efficacy suggest its benefits in first-line therapy of both severe and non-severe AA as well as in management of patients resistant to other methods of immunosuppressive treatment.
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Passaged bone marrow fibroblasts (PBMF) fail to maintain long-term hemopoiesis in culture unlike stromal adhesive layers of long-term culture of the bone marrow (LTCBM). What differs PBMF from LTCBM stromal cells in terms of the above ability we attempted to find out using immunocytochemical microscopy and flow cytometry. There were no differences as to protein production of the extracellular matrix, production of granulocytic-macrophagal colony-stimulating factor, stem cell factor, transforming growth factor beta, interleukin-1 beta and interleukin-6. The difference lies in inability of PBMF to produce granulocytic colony-stimulating factor (GCSF). It is evident that production of GCSF by stromal cells of the bone marrow is essential for maintenance of myelopoiesis in LTCBM.
Macrophagal function of the liver and the spleen has been studied using dynamic scintigraphy in 46 patients with chronic lymphatic and myeloid leukemia. There was an increase in the share of the spleen in total accumulation of radionuclide, shortening of the time of its capture by the liver macrophages and an increase in the indices of hepatic and splenic clearance with the same total time of drug elimination from the blood. The above changes became more distinct with leukemia progression and seem to be more severe in chronic myeloid leukemia.
Bone marrow stromal cells are important sources of cytokines and growth factors which participate in regulation of proliferation and differentiation of hematopoietic stem and progenitor cells. Recently flt3/flk-2-ligand (flt3-L), a new growth factor which uses a membrane tyrosine kinase receptor, was cloned. It is expressed in transmembrane and soluble forms and stimulates/co-stimulates proliferation and colony formation of hematopoietic stem/progenitor cells. It has not been reported whether flt3-L is produced by cells of the hematopoietic bone marrow microenvironment. We demonstrate the expression of flt3-L in bone marrow fibroblasts (BMF) and in stromal cells of adherent layers of long-term bone marrow cultures by RT-PCR, Northern blot, immunocytochemistry and FACS analysis. The latter two methods localized flt3-L intracellularly and on cell membranes. Treatment with interleukin-1 alpha increased the expression of flt3-L in BMF. This demonstrates production and modulation of flt3-L in stromal cells of human bone marrow.
Four patients with acute leukemia suffering from a chronic secondary illness (CSI) which developed 1.5 to 34 months after allogenous transplantation of bone marrow are described. One patient (female) was followed up over time: 14, 15, and 20 months after CSI was diagnosed, the rest patients were examined once, 15.5, 23, and 29 months, respectively, after the disease was diagnosed. Besides visual characterization of the buccal mucosa, results of cytologic examination of smear impressions are presented. Specific features of mucosa involvement at the peak of clinical manifestation of CSI and later, when the rest symptoms of secondary disease to a certain measure regressed, are described. The authors emphasize a similarity between the detected changes in the buccal mucosa and those observed in diseases which might be caused by immunity disorders.
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Inhibition of normal hemopoiesis is a regular finding in acute (AML) and chronic (CML) myelogenous leukemias and functional abnormalities of the hemopoietic microenvironment may be involved in this regard. In order to evaluate this possibility we studied the formation of adherent stromal cell layers (ASCL) in long term bone marrow cultures (LTBMC) of 7 patients with CML and 7 patients with AML and examined the ability of these ASCLs to support hemopoiesis after irradiation and a second inoculation of bone marrow cells. The formation of ASCLs was significantly impaired in CML and AML. These CML patients and 3 AML patients did not form typical ASCLs and the cellularity of these layers was greatly reduced. Colony forming unit granulocyte-macrophage (CFU-GM) production from bone marrow cells seeded on normal irradiated ASCLs peaked at week 3 and then gradually decreased by week 8. In CML and AML cocultures CFU-GM numbers decreased rapidly to zero by weeks 4-6 and did not differ significantly from the control cultures which did not contain preestablished ASCLs beginning from week 3. It is suggested that there may be a functional microenvironmental defect in CML and AML that may play a role in the pathogenesis of inhibition of normal hemopoiesis in these diseases.
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