[Matrix metalloproteinase-9 in plasma of bone marrow aspirates of patients with acute myeloid leukemia and myelodysplastic syndrome].

There was studied the level of matrix metalloproteinase-9 (MMP-9) in plasma of bone marrow aspirates in 87 patients: 39 with acute myeloid leukemia (AML) and 48 myelodysplastic syndrome (MDS). It has been found out an association of the level of MMP-9 in plasma of bone marrow aspirates in patients with AML and MDS with a volume of leukemic mass.

Targeted therapy of polycytemia vera patients.

The discovery of the JAK2V617F mutation was the beginning of a new era in the study of myeloproliferative neoplasms (MPN). In addition to contributing to the understanding of the pathophysiology of Ph-negative MPN, JAK2 mutation has become a new therapeutic target in their treatment. In treatment of PV a new era began the era of targeted therapy, which gave a hope for better treatment outcomes and improved quality of life for patients who are resistant to standard therapy. This work presents literature data on molecular-genetic features of the pathogenesis of polycythemia vera (PV) and new possibilities in the treatment of this disease, literature review about JAKinhibitors, targeted therapy of PV. There are reviewed issues on resistance and intolerance of hydroxycarbamide and interferon (IFN-a) and the definition of the indications for administration of JAK-inhibitors. There are presented data on the efficacy and safety of ruxolitinib, which were proven within the clinical trial RESPONSE.

Role of molecular-genetic abnormalities in pathogenesis and risk stratification of multiple myeloma.

Over the past decades the studies have greatly improved our understanding of the molecular basis of multiple myeloma (MM) and mechanisms of disease progression. The majority of the most widespread chromosomal aberrations, revealing in MM, has independent predictive value and influence on a choice of optimal treatment. There were observed 190 MM patients in hematologic hospitals of St. Petersburg. Genetic anomalies (GA) were detected at 3l,3% of patients and did not depend on their age. Patients with ISS III had a detectability of GA higher than with ISS II and ISS I (48,°% (24/5°), 2l,2% (7/33) and 27,6% (8/29)). Translocation t(ll;l4) was found in 23,3% (3O/129) patients; dell3q - 20,8% (27/13°); dell7p - at 8,4% (7/83); t(4;l4) - at 6,9% (9/13O), that allowed to stratify patients in groups of risk according to mSMART version l. O and 2. O. Median overall survival (OS) modified mSMART l. O in group of standard risk was 7° months, high risk - 47,l months. Median OS mSMART 2. O in group of standard risk was 7° months, intermediate risk - 47 months, high risk - 45 months. OS did not depend on age, clinical manifestations, treatment and other factors.

[The specific features of diagnosis of mixed-phenotype acute leukemia: A combination of B-cell antigen expressions according to the results of flow cytometry and morphological markers of myeloid differentiation in blast cells: A clinical case].

This rare type of acute leukemia, blast cells of which express myeloid and/or lymphoid markers, is mainly diagnosed using flow cytometric findings. The paper describes a clinical case of mixed-phenotype acute leukemia, in which B-cell lymphoid antigen expressions were revealed by a flow cytometric technique, while bone marrow morphological specimens showed the signs of myeloid differentiation specific to blast cells. It is concluded that there is a need for a comprehensive examination of patients with new-onset acute leukemia and for an aggregate analysis of flow cytometric results with morphological and cytochemical findings.

[The specific features of the immunophenotype of blast cells in patients with de novo normal karyotype acute myeloid leukemia and FLT3-ITD mutation].

AIM: To study the specific features of de novo acute myeloid leukemia (AML) with FLT3-ITD mutation. SUBJECTS AND METHODS: The results of examination were analyzed in 101 patients. Bone marrow morphological specimens were stained with Pappenheim stain. The karyotype was investigated using the standard GTG-banding method. Blast cells were immunotyped in a five-color analysis on a Cytomics FC 500 laser flow cytofluorometer. RESULTS: FLT3-ITD mutation was identified in 21 patients who had a varying morphological nature of blasts, different karyotype variants, and frequently additional NPM1 gene mutation. The distinctive property of 10 patients with normal karyotype and FLT3-ITD mutation (without NPM1 gene mutation) was the larger number of cases with high expression of HLA-DR and CD7 than in the control group that included 18 patients with normal karyotype AML without FLT3-ITD nutation: 50% versus 6.2% (p = 0.007) and 100% versus 55.6% (p = 0.014), respectively. CONCLUSION: Normal karyotype AML with FLT3-ITD mutation is a group that is homogeneous in the biological phenotype of leukemia cells.

[Heterogeneity of acute myeloid leukemia with the translocation t(8;21)(q22;q22)].

AIM: To characterize the clinical and hematological variability of acute myeloid leukemia (AML) with t(8;21) and to identify the signs associated with the likelihood of its relapse. SUBJECTS AND METHODS: The results of examining 44 patients aged 11 to 70 years were analyzed; the efficiency of treatment was evaluated in 36. Their karyotypes were studied using the standard GTG method. Polymerase chain reaction (PCR) was employed to assess the mutational status of the FLT3, NPM1, NRAS and c-Kit genes. Qualitative PCR was used to reveal the chimeric transcript RUNX1/RUNX1T1. RESULTS: The M2 variant was verified using the French-American-British classification in 82% of cases. One patient was diagnosed with secondary AML. Additional chromosomal aberrations were found in 50% of the patients. The most common breakages were loss of one of the sex chromosomes (34.1%) and damage of chromosome 9 (16.6%). Gene mutations were detected in single cases. Following 2 7+3 induction chemotherapy (CT) cycles, complete remission (CR) was achieved in 97% of cases (3 patients with cytopenia died). Eight (25%) patients developed a relapse mainly within the first 7 months after achieving CR. The characteristic signs of relapse cases were the inefficiency of the first cycle of remission induction (RI), the absence of high-dose consolidation, damage of chromosome 9, D816V mutation in exone 17 of the c-Kit gene. Antirecurrent CT was ineffective in 5 patients. The median overall survival (OS) in patients with early recurrence was 10 months. That in the patients who were recorded to have CR was not achieved; 5-year OS was 57.8%. Chromosome 9 aberration was ascertained to have a negative impact on OS parameters (p=0.003). CONCLUSION: Patients with AML with t(8;21) is a group heterogeneous with respect to age, the morphological nature of blast cells, the pattern of the disease, the presence and type of additional chromosomal aberrations, mutations in individual genes, and clinical course. Those who are unresponsive to the first RI cycle and have additional chromosome 9 damages should be regarded as potential candidates for allogeneic hematopoietic stem cell transplantation.

[Prognostic value of a number of blood laboratory parameters in the use of erythropoiesis-stimulating agents in anemic patients with lymphoproliferative diseases].

AIM: To clarify the prognostic value of the baseline blood levels of endogenous erythropoietin (EE) and tumor necrosis factor-a (TNF-a) involved in the key components of the pathogenesis of anemia in lymphoproliferative diseases (LPD), the counts of reticulocytes and platelets (hematopoietic preservation indicators) in the use of erythropoiesis-stimulating agents (ESAs) to correct anemia syndrome (AS) in patients with LPD. SUBJECTS AND METHODS: The results of AS treatment with ESAs were analyzed in 48 patients with LPD. A study group comprised patients with chronic lymphocytic leukemia (n=1 3), indolent lymphomas (n=14), and multiple myeloma (n=21). Their hemograms (hemoglobin concentration, red blood cells, packed cell volume, reticulocytes, and platelets) and blood EE and TNF-alpha levels were examined before using ESAs. The hemogram was monitored during treatment. ESAs (eralfon (epoietin alpha) in 21 patients and epres in 27) were subcutaneously injected in a dose of 150 IU/kg thrice weekly (for not more than 16 weeks). A control group included 21 anemic patients with multiple myeloma who did not receive ESAs. Increasing hemoglobin concentrations up to 120 g/l was regarded as a positive response to ESA treatment. RESULTS: By and large, the efficacy of epoietin alpha was 62.5% (61.9% for eralfon and 63.0% for epres), which was significantly higher than that in the control group (23.4%; p<0.05). A number of blood laboratory parameters were found to be of value in predicting the efficacy of ESAs. The patients with the decreased baseline concentrations o EE ( <130 mlU/ml) and TNF- alfa (,15 pg/ml) were ascertained to show a positive response more frequently (80 and 92.9%, respectively; p<0.05) than those with thepredicting the efficacy of ESAs. The patients with the decreased baseline concentrations of EE (<130 mlU/ml) and TNF-a (<15 elevated concentrations of the enzymes in question. In addition, a positive response was more often recorded in patients with reticulocyte counts of more than 1% (77.4%; p<0.05) and platelets of 100-10(9)/1 (70%; p=0.05). CONCLUSION: Estimating the baseline blood levels of EE and TNF-a and the counts of reticulocytes and platelets prior to the use of ESAs enables prediction of the efficiency of erythropoiesis-stimulating therapy in anemic patients with LPD.

[Time course of changes in iron metabolic and oxidative-antioxidative system parameters in patients with acute myeloid leukemia].

AIM: To study an association between iron metabolism, free radical oxidation (FRO), and antioxidative system (AOS) in patients with acute myeloid leukemia (AML) during intensive chemotherapy. SUBJECTS AND METHODS: AML patients (n = 14) with a median age of 46 years received 7+3 courses (n = 3) containing cytarabine > or = 1 g/m2/introduction (n = 8) and myeloablative conditioning regimen before hematopoietic stem cell transplantation (n = 3). The concentrations of iron, ferritin, transferrin saturation (TFS), and malonic dialdehyde and the activity of superoxide dismutase (SOD), ceruloplasmin (CP), and catalase were investigated in their sera. The investigations were performed before and after chemotherapy and during hemopoietic recovery and rehospitalization. RESULTS; After therapy termination, there was a significant increase in TFS (6.8% vs 41.9%; p < 0.0001), which gave way to its reduction during hemopoietic recovery (89.5% vs 96.8%; p = 0.003). The activity of antioxidant enzymes was found to be altered at a time. That of catalase was enhanced throughout cytopenia (3.8 and 3.3 vs 5.7 conventional units (CU)/ml; p = 0.028 and p = 0.011). The lower activity of SOD (21.0 vs 41.0 CU/ml; p = 0.018) and the higher activity of CP (1.1 vs 0.8 g/l) were ascertained when leukocyte count increased up to > or = 1 x 10(9)/l. CONCLUSION: After intensive cytostatic therapy, there was a phasic TFS increase accompanied by the compensatory change in AOS activity, which is aimed at neutralizing FRO products.

[The combination of chronic myeloid leukemia and multiple myeloma in one patient].

The article describes the clinical observation of a patient with simultaneous course of lymphoid and myeloid neoplasms. The patient developed two diseases--chronic myeloid leukemia (CML) and multiple myeloma (MM), which were confirmed by corroborated hemogram, myelogram, immunophenotyping of bone marrow cells, biopsy, immunohistochemical, cytogenetic, biochemical and radiological studies. Target therapy of CML with tyrosine kinase inhibitors (imatinib at the standard dose of 400 mg per day) has provided a complete cytogenetic remission at 6 months and major molecular response at 18 months of treatment. Administration of 2 courses of programmed treatment "BD" > (bortezomib + dexamethasone) resulted in a very good partial response, which was maintained through a year and a half. However, against the background of programmed treatment there were developed complications as polyneuropathy of grade 2, which was treated with thioctacide, milgamy, and anemia of grade 2, successfully treated with epoetin beta. Subsequently, the patient was administered continuously with imatinib 400 mg that kept the major molecular response. Relapsed MM was revealed in 20 months and confirmed by a full clinical and hematological examination. The absence of organ dysfunction allowed choosing a supervisory tactics for the patient.

[Cytogenetic profile in patients with primary myelodysplastic syndrome].

AIM: To analyze the prevalence of chromosome aberrations presented in the revised International Prognostic Scoring System (R-IPSS) in patients with de novo myelodysplastic syndrome (MDS). Subjects and methods. Chromosome aberrations were analyzed in 197 patients aged 14 to 86 years (median age 64 years) with de novo MDS. RESULTS: Karyotype abnormalities were revealed in 129 (65.5%) patients with de novo MDS. According to the IPSS criteria, the karyotypes found 52 (26.4%) patients were assigned to an intermediate prognostic group whereas in accordance with the R-IPSS guidelines, an intermediate karyotype group included chromosome abnormalities in 32 (16.2%) patients. Out of 5 R-IPSS prognostic types, the favorable karyotype group was the largest (48.2%). The very favorable and unfavorable karyotype groups comprised few patients with MDS: 3 and 3.6%, respectively. Despite the fact that it was not mentioned in the R-IPSS, a monosomal karyotype was verified in 24 (12.2%) patients There was a correlation of the (normal and complex) karyotype with bone marrow blast counts (r=0.469; p=0.000), but not with age. CONCLUSION: A variety of cytogenetic damages cannot identify the prognostic potential of all chromosome aberrations occurring in patients with MDS even if prognostic factors increased up to 5.

[Complex karyotype is a marker of very poor prognosis in over 70-year-old patients with acute myeloid leukemia and extended types of myelodysplastic syndrome and high comorbidity index].

AIM: To identify a category of persons with very low overall survival (OS) rates, whose intensive chemotherapy is unreasonable, amongst the patients with acute myeloid leukemia (AML) with extended forms of myelodysplastic syndrome (MDS) and complex karyotype. MATERIALS AND METHODS: OS rates were retrospectively analyzed in 41 patients with AML and 26 with MDS; their median age was 61 years (range 15 to 77 years). Thirty-four (50.7%) patients received standard induction courses; 19 (28.4%) patients had low-intensity therapy. Restraining therapy was used to treat 14 (20.9%) patients. The length of follow-up was 1.5 to 171 months. RESULTS: Irrespective of the type of disease, the median OS was 6 months. A difference in OS was found when the patients were divided into 4 age groups: those who were under 40 years of age (n = 11 ), 41-60 years (n = 21), 61-69 years (n = 21), and > or = 70 years (n = 14). With age, the median OS decreased from 9.5 to 4 months (p = 0.041). Multivariate analysis revealed that the intensity of induction courses was the cause that affected OS. High comorbidity index and, first of all, cardiovascular diseases were the main reason for discontinuing standard chemotherapy courses in patients aged 70 years or older. CONCLUSION: Standard induction courses of cytostatic therapy are not indicated for patients aged > or = 70 years with AML and extended stages of MDS with complex karyotype and high comorbidity index.

[Age-specific characteristics of acute myeloid leukemia karyotype].

AIM: To study distribution of some karyotype variants among patients of different age with acute myeloid leukemia (AML). MATERIAL AND METHODS: Distribution of balanced, normal, unbalanced, complex and monosomic karyotype among 244 patients with de novo AML in age groups 16-20, 21-30, 31-40, 41-50, 51-60, 61 and older was analysed. RESULTS: There is difference in frequency of balanced and complex karyotype in patients under and over 60 years. Number of AML patients with balanced aberrations including favourable variants t(8;21), t(15;17) and inv(16) falls after 60 years of age (6.7% versus 15.0% in patients aged 16-20 years; p < 0.001), while a complex karyotype occurs more frequently in AML patients at the age of 61 and older (56.8% versus 2.7% in the group 16-20 years; p < 0.001). With age, more frequently detected is the most unfavourable monosomic karyotype with aberrations similar to those in myelodysplastic syndrome (57.1% in patients aged 16-60 years and in 80.0% in the group of 61 years of age and over). CONCLUSION: Age-specific karyotype features detected may be explained by different biological mechanisms involved in leukosogenesis in young and elderly AML patients.

[FLT3 and NPM1 gene mutations in patients with acute myeloid leukemias and the impact of FLT3-ITD mutations on the survival of patients with a normal karyotype].

AIM: To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML). MATERIALS AND METHODS: The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied. RESULTS: Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1 and FLT3-ITD+/ NPM-T genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-1TD mutation on EFS. CONCLUSION: The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM-genotypes to be identified as a poor prognosis group.

[Investigation of FLT3-ITD and NPM1 mutations in patients with myelodysplastic syndrome and mixed myeloid diseases].

Two FLT3-ITD mutations, one FLT3-TKD) and five NPM1 mutations were detected in 7 patients with de novo myelodysplastic syndrome (MDS) out of 44 cases of MDS and MDS/mixed myeloid diseases. Expression of one of the three investigated mutations was identified: 4 in gene NPM1 (9.1%) and 2--FLT3-ITD (4.5%); simultaneous FLT3-ITD and NPM1 mutation--1 (2.3%); no progression in NPM1 within 9-20 months--3, although with chromosome 7 damage--2. It was suggested that NPM1 mutation without complex karyotype may serve as marker of relatively favorable course.

[Prognosis factors in imatinib mesilate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia].

AIM: To reveal prognostically significant factors affecting efficacy of glivek therapy in untreated (duration of the disease < or = 6 months) and pretreated (duration of the disease > 6 months) patients with chronic myeloid leukemia (CML) in a chronic phase. MATERIAL AND METHODS: A total of 338 patients (64 untreated and 274 pretreated) with a chronic-phase CML on glivek therapy entered the trial. RESULTS: Five-year survival on glivek was high (89, 98 and 88% in untreated and pretreated patients, respectively). Incidence of transformation in the acceleration phase and blast crisis was low both in untreated and pretreated patients (1.6 and 11%, respectively) and correlated with the rate of a complete cytogenetic response (CCR). Untreated patients had no factors affecting treatment efficacy negatively, CCR probability was 96%. Blastemia, thrombocytosis and splenomegaly reduced CCR probability significantly in pretreated patients. Slow reduction of the tumor mass, late achievement of a complete hematological response and a cytogenetic response decreased probability of CCR. CONCLUSION: Glivek is a drug of choice for patients with chronic-phase CML. High probability of CCR both in untreated and pretreated patients lowers the risk of the disease transformation into the phase of acceleration/blast crisis and raises overall survival in both groups.

Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies.

PURPOSE: To investigate the effect of recombinant human erythropoietin (epoetin beta) on anemia, transfusion need, and quality of life (QOL) in severely anemic patients with low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma (MM). PATIENTS AND METHODS: Transfusion-dependent patients with NHL (n = 106), CLL (n = 126), or MM (n = 117) and a low serum erythropoietin concentration were randomized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks. Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival (hemoglobin [Hb] > 8.5 g/dL) between weeks 5 to 16. Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need. QOL was assessed by the Functional Assessment of Cancer Therapy scale. RESULTS: Transfusion-free (P =.0012) survival and transfusion- and severe anemia-free survival (P =.0001) were significantly greater in the epoetin beta group versus placebo (Wald chi(2) test), giving a relative risk reduction of 43% and 51%, respectively. The response rate was 67% and 27% in the epoetin beta versus the placebo group, respectively (P <.0001). After 12 and 16 weeks of treatment, QOL significantly improved in the epoetin beta group compared with placebo (P <.05); this improvement correlated with an increase in Hb concentration (> or = 2 g/dL). A target Hb that could be generally recommended could not be identified. CONCLUSION: Many severely anemic and transfusion-dependent patients with advanced MM, NHL, and CLL and a low performance status benefited from epoetin therapy, with elimination of severe anemia and transfusion need, and improvement in QOL.

[Clinical significance of lymphocyte subpopulations and cytokine-producing activity of blood cells in patients with primary myelodysplastic syndrome].

Lymphocyte subpopulation composition and spontaneous production of tumor necrosis factor-alpha (TNF-alpha) by blood cells were studied in 22 and 15 patients with myelodysplastic syndrome (MDS), respectively, who were under immunosuppressive therapy (IST). Patients with hematological response revealed a significantly increased cytotoxic CD8+ lymphocyte concentration and TNF-alpha production. A direct correlation between TNF-alpha production rate and CD8+ lymphocyte level was established. Maximum cytokine-producing activity of blood cells was identified in MDS patients with enhanced erythroid response. The study established a great diversity of MDS, its hypoplastic variants and the prognostic value of spontaneous production of tumor necrosis factor-alpha (TNF-alpha) by blood cells as marker of IST efficacy.

[Prognostic potential of morphological and cytogenetic indices in patients with myelodysplastic syndrome].

AIM: To examine prognostic potential of the number of bone marrow (BM) blasts and cell karyotype as risk factors of transformation of myelodysplastic syndrome (MDS) in acute myeloblastic leukemia AML. MATERIAL AND METHOD: The analysis of examination was made for 72 patients with primary MDS in the groups formed by number of blasts in BM, karyotype and IPSS variant. MDS was diagnosed by WHO criteria. Transformation into AML was established in blastosis > 20% in peripheral blood and/or BM. The karyotype was studied according to GTG technique. RESULTS: More frequent progression of MDS was seen in patients with blastosis > 10%, unfavourable karyotype and high IPSS risk. The least number of leukemic transformations occurred in karyotype of intermediate prognosis while disease-free survival in patients with karyotype of good prognosis was similar to that of patients with unfavourable karyotype. The number of blasts in BM and IPSS variant appeared to be prognostic markers of duration of leukemia-free survival in one-factor analysis. The multifactorial analysis found out one factor of MDS transformation in AML: number of blasts in BM puncture biopsy. CONCLUSION: Prognostic priority of the number of BM blasts as a risk factor of MDS progression compared to karyotype is explained by biological heterogenicity of MDS.

[The prognostic role of determining spontaneous leukocyte DNA damage and that occurring during chemotherapy in leukemia patients]. / Prognosticheskaia rol' opredeleniia spontannykh i voznikaiushchikh v protsesse khimioterapii povrezhdenii DNK leikotsitov bol'nykh leikozami.

The authors studied spontaneous DNA damages and the extra plan synthesis of DNA in various leukemias (chronic lympholeukemia, chronic myeloleukemia, acute leukemia) to predict the natural course of leukemias and the efficiency of chemotherapy. The level of genuine DNA breaks, which had been determined by the nic-translation test, was lower in peripheral blood cell DNA in all leukemias than that in the lymphocytes and granulocytes from donors. On the contrary, the levels of alkaline-labile DNA sites and nuclear matrix protein-bound DNA in the mature and maturing leukemia cells are high and decrease with progression of chronic lympholeukemia and chronic myeloleukemia. The extra plan DNA synthesis largely reflects the cellular levels of genuine DNA breaks, and the ultraviolet-induced DNA repair capacity is the highest in the lymphocytes in chronic lympholeukemia and particularly in the blasts in acute leukemia. The efficiency of chemotherapy was predicted during chemotherapy from the intensity of formation of genuine blast cell DNA breaks.

[The colony-forming capacity of the precursor cells of granulomonocytopoesis in bone marrow aplasia]. / Kolonieobrazuiushchaia sposobnost' kletok-predshestvennikov granulomonotsitopoéza v usloviiakh aplazii kostnogo mozga.

Retrospective analysis of 80 patients with aplastic anaemia (AA) was performed in order to examine clonogenic properties of granulomonocytopoiesis precursors and to specify the extent of disorder of hemopoiesis in AA. Sharp decrease of clonogenic properties of precursors, especially in severe form of AA was established to be present in 95% of patients, while only in 5% of patients initial indexes of the clonogenic ability were discovered to be normal. After treatment with ALG, prednisolum and androgen and also after splenectomy, clonogenic ability increased appropriately in 43%, 16.6% and 76.9% of patients, although the effect was not steady. The best results were obtained after allogenic transplantation of bone marrow (TBM), when the clonogenic properties normalization was observed against the background of remission 1-3 years lasted. Thus, low indexes of clonogenic properties of the precursors of granulomonocytopoiesis in AA, and positive effect of TBM may indicate the lesion of the precursor. At the same time normal initial indexes in some patients, and diverse effect of different methods of therapy make it possible to admit the probability of the lesion of stromal microenvironment cells.