Vol 85, No 7 (2013)

Editorial
Therapeutic strategy for chronic myeloid leukemia: possibilities and prospects
Turkina A.G., Chelysheva E.I.
Abstract
Over the past decade the clinical introduction of agents that directionally blocks the activity of BCR-ABL tumor tyrosine kinase (TK) has changed the prognosis of chronic myeloid leukemia. A significant malignant Ph'-positive clone inhibition and durable remissions have made it possible to increase overall and relapse-free survival. Due to their higher life expectancy, the number of patients is on the increase and their quality of life and working capacity remain good. According to the All-Russian Register of Chronic Myeloid Leukemia, there were more than 6500 cases in the Russian Federation in 2012. Of them, 93.1% were diagnosed with the chronic phase of the disease, 6.4 and 0.4% with its accelerated phase and blast crisis, respectively. Among the BCR-ABL TK inhibitors (TKI) registered in the Russian Federation and recommended for the treatment of chronic myeloid leukemia, there are 3 medications: imatinib, nilotinib, and dasatinib. The efficiency and safety of TKI therapy have been well studied. The most important principle of treatment is to permanently affect the Ph'-positive tumor cell clone by the long-term daily use of TKIs. Regular cytogenetic and molecular genetic monitoring allows adequate estimation of the leukemic clone volume and it is essential in evaluating the therapeutic effectiveness. To choose a TKI for each specific patient with regard for its best tolerability and maximum efficiency permits individualized treatment. The prospect of therapy discontinuation can be discussed only in individual patients with a durable and stable complete molecular response and only within clinical trials.
Terapevticheskii arkhiv. 2013;85(7):4-9
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Treatment of adult patients with acute promyelocytic leukemia according to the AIDA protocol
Parovichnikova E.N., Troitskaia V.V., Sokolov A.N., Kliasova G.A., Galstian G.M., Kuz'mina L.A., Domracheva E.V., Dvirnyk V.N., Savchenko V.G.
Abstract
AIM: To give the results of an investigation conducted at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), to treat adult patients with acute promyelocytic leukemia (APL) according to the AIDA protocol elaborated by Spanish investigators/MATERIAL AND METHODS: The investigation enrolled 33 patients diagnosed with APL verified by cytogenetic and molecular studies, who had been treated at the HRC, MHRF, in July 2009 to January 2012. The patients classified in the low-, intermediate-, and high-risk groups were 30, 46.7; and 23.3%, respectively. The analysis was made in January 2013/RESULTS: The number of patients who achieved complete remission, as well as the mortality rates during remission induction were wholly comparable to those previously obtained when using the 7+3+ATRA protocol: 90.3 and 9.7%, respectively. One patient in remission died (3.6% mortality rate). The likelihood of recurrence in this investigation was high (21%), which was due to gross noncompliance with maintenance therapy. On examining the clearance of the malignant clone by FISH and polymerase chain reaction, a naturally chimeric transcript identified by a molecular study was statistically significantly more frequently revealed during postinduction therapy, which was associated with different sensitivity of the techniques. Comparison of changes in the disappearance of a chimeric marker for APL with the AIDA and 7+3+ARTA programs showed that the clearance of the malignant clone was much slower/CONCLUSION: The AIDA program is a highly effective treatment protocol for patients with APL.
Terapevticheskii arkhiv. 2013;85(7):10-17
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Allogeneic hematopoietic stem cell transplantation for acute myeloblastic leukemia in first remission
Bondarenko S.N., Semenova E.V., Vavilov V.N., Stancheva N.V., Morozova E.V., Alianskiĭ A.L., Babenko E.V., Osipova N.É., Zubarovskaia L.S., Afanas'ev B.V.
Abstract
AIM: To evaluate the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloblastic leukemia in first remission depending on the regimens of conditioning, the source of a graft, and the characteristics of a donor and a recipient/MATERIAL AND METHODS: In 66 treated patients, including from partially HLA-mismatched relatives (n=4), the efficiency of allo-HSCT from related donors (n=26) and unrelated donors (n=40), were compared. According to cytogenetic findings, 7 (11%), 31 (47%), and 10 (15%) patients belonged to low-, intermediate-, and high-risk groups, respectively/RESULTS: Five-year overall survival (OS) and mortality associated with transplantation were 56 and 22% for allo-HSCT from related donors, 68 and 23% for that from HLA-matched donors, and 71 and 25% for that from partially HLA-mismatched donors, respectively (p=0.8 and p=0.7). The relapse risk after allo-HSCT from unrelated donors was significantly lower than after that from related donors (13 and 35%, respectively; p=0.8). Univariate analysis showed that the OS rates depended on the cytogenetic risk group (OS was 24 and 64% in the high- and intermediate-risk groups, respectively (p=0.027). The relapse risk in chronic graft-versus-host reaction (GVHR) and in grade 3 acute GVHR (p=0.01) was shown to be less than that in grades 1-2 acute GVHR (p=0.06)/CONCLUSION: OS rates after allo-HSCT from related and unrelated donors were comparable and unrelated to the source of a graft, the regimen of conditioning, and other characteristics of a donor and a recipient.
Terapevticheskii arkhiv. 2013;85(7):18-25
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Efficacy of donor lymphocyte infusion in patients after different types of allogeneic hematopoietic stem cell transplantation
Slesarchuk O.A., Babenko E.V., Semenova E.V., Bondarenko S.N., Éstrina M.A., Morozova E.V., Paina O.V., Vavilov V.N., Smirnov B.I., Zubarovskaia L.S., Afanas'ev B.V.
Abstract
AIM: To evaluate the efficacy of donor lymphocyte infusion (DLI) to prevent and treat recurrences in patients after different types of allogeneic hematopoietic stem cell transplantation (allo-HSCT)/MATERIAL AND METHODS: Data from 118 patients with malignant blood diseases were analyzed. Allo-HSCTs from HLA-matched related donors (n=49), HLA-matched unrelated donors (n=50), partially HLA-matched unrelated donors (n=2), and haploidentical donors (n=24) were performed. The indications for DLI were underlying disease relapse (59 DLIs), resistant disease course (n=40), minimal residual disease (n=16), falling donor chimerism (n=15), and recurrence prevention (n=13)/RESULTS: Therapy response was obtained after 57 (44%) DLIs. There were 36 (25%) and 30 (21%) cases of acute and chronic graft-versus-host reactions (GVHR), respectively. The use of DLI from HLA-matched donors, its performance in the periods of D+100 to one year after allo-HSCT, a donor chimerism level of over 90% at the moment of DLI, the administration of the initial DLI dose of below 1·106 CD3+/kg, and the development of chronic GVHR after DLI were associated with the highest rate of therapy responses. The overall survival rates of patients with DLI were significantly influenced by factors, such as DLI periods, donor chimerism levels at DLI, and the development of chronic GVHR after DLI/CONCLUSION: The choice of the optimal dose of cells, the periods of DLI and its preventive administration improve prognosis in patients after allo-HSCT. The occurrence of acute GVHR is affected by the degree of HLA matching and the type of a donor. The development of chronic GVHR after DLI is associated with the highest rate of responses to DLI and higher survival rates.
Terapevticheskii arkhiv. 2013;85(7):26-33
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Cytogenetic characteristics of hematopoietic and stromal progenitor cells in myelodysplastic syndrome
Pimenova M.A., Parovichnikova E.N., Kokhno A.V., Domracheva E.V., Manakova T.E., Mal'tseva I.S., Konnova M.L., Shishigina L.A., Savchenko V.G.
Abstract
AIM: To study and compare cytogenetic abnormalities in the bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS)/MATERIAL AND METHODS: The results of a cytogenetic analysis of the total population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors. Cytogenetic examinations were performed by G-banding of chromosomes and fluorescence in situ hybridization (FISH)/RESULTS: The BMC karyotype was abnormal in 17 (49%) of the 35 patients (13 with MDS and 4 with AML); the others were found to have a normal BM karyotype. The FISH analysis confirmed the same cytogenetic abnormalities in the BM and PB CD34+ hematopoietic progenitor cells in all the examinees with an abnormal karyotype. The mean abnormal clone sizes in the total population of BMCs and BM and PB CD34+ progenitor cells did not differ and constituted 65.8, 73.1, and 74.8%, respectively. The patients with a normal BM karyotype had no chromosome abnormalities in the CD34+ cells either. The karyotype of MSCs was analyzed in 23 (19 with MDS and 4 with AML) of the 35 patients. No karyotype abnormalities were revealed in the patients with MDS transformed into AML. There were structural chromosome aberrations in 2 (11%) of the 19 patients with MDS (one with constitutional inv(9)(p13q21) was found to have non-clonal translocation t(2;22)(p10;q11) and the other had a clone with an additional segment of the long arm of chromosome 2 in 35% of the cells. No numerical MSC karyotype abnormalities were detected. A normal MSC karyotype was defined in 7 healthy BM donors/CONCLUSION: The cytogenetic analysis of hematopoietic and mesenchymal progenitor cells showed that the chromosome abnormalities revealed in these cell populations were different in the patients with MDS. The isolated CD34+ cells displayed the same cytogenetic abnormalities as in a total population of BMC. Examination of the latter could reveal no cytogenetic abnormalities in the majority of the patients. A normal BMC karyotype was detectable in the patients with AML. Two (11%) patients with MDS were found to have structural chromosome abnormalities that differed from those detected in the total population of BMC and in isolated CD34+ cells. The differences of chromosome abnormalities in the hematopoietic and mesenchymal progenitor cells point to the fact that the stromal microenvironment is not part of the abnormal clone in MDS, however, it may be of great importance in the pathogenesis of the disease.
Terapevticheskii arkhiv. 2013;85(7):34-42
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Cytogenetic profile in patients with primary myelodysplastic syndrome
Gritsaev S.V., Martynkevich I.S., Petrova E.V., Martynenko L.S., Ivanova M.P., Aksenova V.I., Tsybakova N.I., Potikhonova N.A., Abdulkadyrov K.M.
Abstract
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)/MATERIAL 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.
Terapevticheskii arkhiv. 2013;85(7):43-49
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Eight-year experience in treating aggressive mediastinal large B-cell lymphomas
Mangasarova I.K., Magomedova A.U., Kravchenko S.K., Shmakov R.G., Bariakh E.A., Vorob'ev V.I., Mar'in D.S., Skidan N.I., Gemdzhian É.G., Misiurin A.V., Kremenetskaia A.M., Vorob'ev A.I.
Abstract
AIM: To make a differential diagnosis of diffuse large B-cell lymphoma (DLBCL) with primary involvement of the mediastinal lymph nodes (LN) and primary mediastinal large B-cell lymphoma (PMLBCL); to evaluate the efficiency of a modified NHL-BFM-90 (M-NHL-BFM-90) program in the treatment of the above nosological entities/MATERIAL AND METHODS: The investigation enrolled 60 patients with large B-cell lymphoma (LBCL) with primary involvement of mediastinal LN who had been treated at the Hematology Research Center, Ministry of Health of Russia, in 2004 to 2012. The diagnosis of PMLBCL and DLBCL with primary involvement of mediastinal LN was based on histological findings, the phenotype of tumor cells, and molecular evidence. Treatment was performed according to the M-NHL-BFM-90 program. Three pregnant women received predelivery polychemotherapy (PCT) according to the VACOP-B protocol and continued to have a DexaBEAM chemotherapy regimen 3-4 weeks postpartum. In case of a residual mass, all the patients underwent consolidation radiotherapy to the mediastinal area in a total focal dose of 36 Gy/RESULTS: The diagnosis of PMLBCL was established in 39 patients: 10 men and 29 women whose ages were 18 to 60 years (median age 30 years); DLBCL with primary involvement of mediastinal LN was verified in 21 patients: 8 men and 13 women whose age was 21 to 70 years (median age 30 years). After m-NHL-BFM-90 treatment protocol, 5-year overall survival rates in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL were 95±5 and 86±6% and 5-year event-free survival rates were 95±5 and 78±7%, respectively. All the pregnant women diagnosed with PMLBCL who had received the VACOP-B ⇒ delivery ⇒ Dexa-BEAM PCT regimen during pregnancy achieved remission. The follow-up periods were 30, 36, and 42 weeks/CONCLUSION: The patients with new-onset LBCL and primary involvement of mediastinal LN are a heterogeneous group that includes patients having two different diagnoses: PMLBCL and DLBCL. The efficiency of high-dose PCT is different in the patients with DLBCL with primary involvement of mediastinal LN and in those with PMLBCL (in spite of their similar clinical features, similar epidemiological characteristics, and the presence of the same unfavorable prognostic factors at onset).
Terapevticheskii arkhiv. 2013;85(7):50-56
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Evaluation of tumor vascularization and microenvironment in follicular lymphoma
Nesterova E.S., Kravchenko S.K., Gemdzhian É.G., Osmanov E.A., Kovrigina A.M.
Abstract
AIM: To characterize the degree of follicular lymphoma (FL) vascularization and microenvironment by immunohistochemical studies (IHCS) of lymph node biopsy paraffin-embedded sections in 2 different disease pattern groups/MATERIAL AND METHODS: The investigation included 59 patients: 39 (67%) women and 20 (33%) men whose age was 27 to 83 years (median age 53 years) treated at the Hematology Research Center, Ministry of Health of the Russian Federation (n=49), and the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences (n=10), in April 2001 to May 2011. In accordance with the clinical features of the disease, the authors identified 2 patient groups: 1) 31 patients with the good results of FL treatment and 2) 28 patients with its poo/RESULTS: IHCS was performed on lymph node tumor biopsy paraffin-embedded sections prior to treatment using antibodies to CD34, D2-40, CD68, and granzyme B. Morphometric analysis was made applying microscopy and a Leica ×400 digital camera. The images of histological specimens were processed by the computer program VideoTesT-Morphology 5.2: the specific vessel area (%) in relation with tumor tissue was estimated under visual guidance of an investigator. Cytotoxic lymphocytes (CTL) and macrophages were quantitatively characterized using 1 mm2 of tumor tissue (12 fields of vision with the objective lens magnifying ×400). Immunohistochemical specimens to be examined were chosen randomly, by using the random number table/RESULTS: In Group 2, the specific area of blood vessels was statistically significantly higher than in Group 1: 0.04% (95% confidence interval (CI), 0.03 to 0.05%) versus 0.02% (95% CI, 0.01 to 0.03%; p=0.05). In Group 2, that of lymphatic vessels was significantly higher than in Group 1: 0.06% (95% CI, 0.04 to 0.07%) versus 0.03% (95% CI, 0.01 to 4%; p=0.03). With a nodular diffuse growth, Group 2 showed a significantly more CD68-positive macrophages than did Group 1: 800 (95% CI, 380 to 1222) versus 79 (95% CI, 10 to 566; р=0.01). In Group 1, the count of CTL was statistically significantly (p=0.05) higher than in Group 2 in both the nodule (with a nodular growth pattern: 14 (5-27) versus 5 (1-11)) and the internodular space (with a nodular growth pattern: 158 (118-410) versus 35 (5-287) and with a nodular diffuse growth pattern: 126 (102-360) versus 35 (3-120))/CONCLUSION: Increased tumor vascularization (estimated by the specific density of tumor vasculature) and a pronounced macrophageal reaction are associated with the poor outcomes of FL; the marked cytotoxic component in tumor tissue is linked to the favorable outcomes of the disease.
Terapevticheskii arkhiv. 2013;85(7):57-64
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Morphological evaluation of dysmyelopoiesis in decitabine-treated patients with myelodysplastic syndromes
Dvirnyk V.N., Kokhno A.V., Glasko E.N., Gemdzhian É.G., Diagileva O.A., Platonova T.L., Parovichnikova E.N.
Abstract
AIM: To estimate a change in myelodysplasia in decitabine-treated patients with myelodysplastic syndromes (MDS)/MATERIAL AND METHODS: Thirteen MDS patients from a high-risk group were examined; 75 bone marrow puncture specimens and 67 bone marrow trepanobiopsy specimens from these patients were analyzed before and after decitabine treatment. Dysplastic changes in the hematopoietic cells were monitored during the treatment/RESULTS: The dysplastic changes in the hematopoietic cells are a morphological portrayal of the ineffective hematopoiesis in patients with MDS. The study has indicated that the use of the hypomethylating agent decitabine promotes the restoration of cell differentiation to mature forms, causing hematopoiesis to be more effective. The incidence of myelodysplasias (including mixed double- and triple-lineage ones) was statistically significantly reduced by decitabine treatment, which was associated with a positive response to treatment as a whole. The count of cells with dysplastic features remained unchanged in patients with therapy resistance or further disease progression/CONCLUSION: Analysis of myelodysplastic manifestations in different hematopoietic lineages in patients with MDS should be based on the comprehensive dynamic assessment of cytological and histological parameters at both the primary diagnosis of the disease and different stages of treatment. With a response to decitabine therapy (as shown by the results of aspiration and trepanobiopsy), all cell lines displayed reduced myelodysplastic changes, indirectly indicating a decrease of the abnormal clone itself in high-risk MDS patients.
Terapevticheskii arkhiv. 2013;85(7):65-71
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Characterization of the genotypes of patients with Gaucher disease type 1 in the Russian Federation
Lukina K.A., Fevraleva I.S., Sysoeva E.P., Mamonov V.E., Sudarikov A.B., Lukina E.A.
Abstract
AIM: To characterize the genotype and genotype-phenotype correlations in patients with Gaucher disease (GD) in the Russian Federation. Materials and methods. One hundred adult patients with GD type 1 were examined. Their clinical study encompassed the evaluation of the severity of osteoarticular lesions from instrumental findings. An allele-specific real-time polymerase chain reaction assay was used to screen four most common acid Β-glucoside gene (GBA) mutations (N370S, 84GG, L444P, IVS2+1)/RESULTS: The N370S mutation and the N370S/? genotype where the second allele was presented with the mutation outside the 4 most common GBA gene mutations were found in the Russian patients with GD. Analysis of the clinical manifestations of the disease revealed no association between the genotype under examination and the severity of osteoarticular lesions and supported the unfavorable role of splenectomy (SE) in the development of severe bony disease/CONCLUSION: SE should be carried out in patients with unclear cytopenia and splenomegaly after the diagnosis of GD is excluded. The GD patients undergoing SE should receive emergency enzyme replacement therapy to prevent severe osteoarticular lesions and an irreversible orthopedic defect.
Terapevticheskii arkhiv. 2013;85(7):72-75
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Successful use of vemurafenib in a patient with resistant hairy cell leukemia
Urnova E.S., Al'-Radi L.S., Kuz'mina L.A., Kariakina A.A., Kovrigina A.M., Dvirnyk V.N., Iakutik I.A., Sudarikov A.B., Parovichnikova E.N., Savchenko V.G.
Abstract
The paper describes a case of a patient with refractory hairy cell leukemia. In spite of the absence of CD25 expression, the disease was classified as a classical form according to the WHO classification (2008), as also confirmed by the detection of BRAFV600E mutation. The disease was characterized by resistance to all lines of therapy (interferon-α, splenectomy, cladribin). Clinical and hematological remission was achieved within 2 months of administration of the BRAF kinase inhibitor vemurafenib.
Terapevticheskii arkhiv. 2013;85(7):76-78
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Successful therapy for enteropathy-associated peripheral T-cell lymphoma using high-dose polychemotherapy and autologous hematopoietic stem cell transplantation
Vorob'ev V.I., Kravchenko S.K., Kovrigina A.M.
Abstract
Enteropathy-associated T-cell lymphoma (EATL) is a rare disease that accounts for not more than 1.4% of all lymphomas. It is most common in Europe, followed by North America and Asia. The disease is associated with gluten-sensitive celiac disease in 50% of cases and divided into types I and II. Mean-dose CHOP-like therapy is ineffective, with a median overall survival of 7-10 months. With high-dose therapy, 5-year survival rates can be 60%, but it can be used in not more than half of the cases. This is associated with the serious somatic status of most patients at diagnosis and with a median age of 57-64 years. The article presents a literature review and a case of successful therapy in a 58-year-old patient with type I EATL using the mNHL-BFM-90 protocol and autologous hematopoietic stem cell transplantation.
Terapevticheskii arkhiv. 2013;85(7):79-83
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Multiple myeloma predominantly involving the spleen
Ryzhko V.V., Klodzinskiĭ A.A., Grachev A.E., Varlamova E.I., Sataeva M.S., Nakastoev I.M.
Abstract
Extramedullary disease is an uncommon manifestation in multiple myeloma (MM) and can be observed at onset or develop at disease progression or relapse. Splenic involvement is very rare. The paper describes a 52-year-old female patient with MM who in 1990 was diagnosed with monoclonal gammopathy of undetermined significance with IgGκ secretion and a considerably enlarged spleen. Specific therapy with bortezomib and dexamethasone was initiated in 2006 and proved to be inefficient. After splenectomy there was a 50% reduction in IgGκ concentration. Splenic histological examination revealed monoclonal infiltration by the pleomorphic plasma cells expressing a kappa light chain.
Terapevticheskii arkhiv. 2013;85(7):84-86
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Tuberculous sacroiliitis in a patient with Gaucher disease
Lukina E.A., Mamonov V.E., Lukina K.A., Khomenko V.A., Pisetskiĭ M.M., Iatsyk G.A.
Abstract
Gaucher disease (GD) is an inherited enzymatic defect resulting from a deficiency of acid Β-glucosidase, a lysosomal enzyme involved in the degradation of cell metabolic products. The major clinical manifestations of GD are hepatosplenomegaly, cytopenia, and bony involvement varying from asymptomatic osteopenia to severest osteoporosis and ischemic necrosis to develop irreversible orthopedic defects. Timely enzyme replacement therapy with recombinant glucosidase makes it possible to arrest disease progression and to prevent damage to the vital organs. However, GD in adult patients is frequently diagnosed in the presence of occurring osteoarticular lesions (arthrosis deformans, abnormal fractures). In these instances, besides enzyme replacement therapy, high-quality orthopedic care is required. The description of the case history of a patient undergoing splenectomy in childhood is given as a clinical example of severe osteoarticular lesion in GD and complex differential diagnosis with the intercurrent disease extrapulmonary tuberculosis.
Terapevticheskii arkhiv. 2013;85(7):87-89
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Role of high-dose chemotherapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma
Gavrilina O.A., Gabeeva N.G., Morozova A.K., Sidorova A.A., Zvonkov E.E.
Abstract
High-dose chemotherapy (HD-CT) in combination with autologous stem cell transplantation (auto-SCT) has long become the gold standard treatment for chemosensitive recurrences and refractory diffuse large B-cell lymphoma (DLBCL). By taking into account the low efficiency of rescue therapy (postrecurrence five-year survival rate is not more than 10-20%), it is clear that the results of treatment should be improved in the induction of the first remission. The study performed in the rituximab time showed the higher efficiency of first-line therapy using auto-SCT. Therapeutic effectiveness was also noted to depend on the intensity of pretransplantation regimens. Indications for HD-CT with auto-SCT must be substantiated because of the higher toxicity together with therapy intensification. Conventional clinical criteria for this are insufficient. Thus, it is necessary to search for new molecular genetic prognostic factors that will be able to portray tumor biology.
Terapevticheskii arkhiv. 2013;85(7):90-97
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Gene expression of vascular endothelial growth factors and their receptors in different variants of the course of multiple myeloma
Golenkov A.K., Buravtsova I.V., Dudina G.A., Lutskaia T.D., Mitina T.A., Kataeva E.V., Karamysheva A.F., Kakpakova E.S., Sablina I.A., Stavrovskaia A.A.
Abstract
AIM: To determine the significance of the angiogenic activity estimated from the gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFR1s, VEGFR2, and VEGFR3 in the mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells predominating in different variants of the course of multiple myeloma (MM). Materials and methods. The gene expression of VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFR1s, VEGFR2, and VEGFR3 was determined by reverse-transcription polymerase chain reaction (RT-PCR)/RESULTS: VEGF-A, VEGF-C, VEGF-D, as well as VEGFR1, VEGFR1s, VEGFR2, and VEGFR3 were expressed showing different intensities in the mononuclear cell fraction of BM aspirates with a predominance of tumor plasma cells in the patients with MM, which allowed patient groups to be identified. In the group of high gene expression of VEGFs and their receptors, the number of clusters of plasma cells and vascular endothelium in the BM aspirates and the degree of osteolysis in the skeletal bones of patients with MM were significantly higher than those in the group of low or absent gene expression. The survival in the latter group was significantly higher/CONCLUSION: The investigation could provide an estimate of angiogenic processes in MM and establish their association with clinical manifestations and cytological characteristics.
Terapevticheskii arkhiv. 2013;85(7):98-102
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