Vol 82, No 7 (2010)


Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies

Parovichnikova E.N., Savchenko S.A., Klyasova G.A., Isayev V.G., Sokolov A.N., Kulikov S.M., Ustinova E.N., Gribanova E.O., Ryzhko V.V., Khorosko N.D., Kravchenko S.K., Galstyan G.M., Konstantinova T.S., Zagoskina T.P., Zyuzgin I.S., Kaplanov K.D., Moskov V.I., Sokolova I.V., Anchukova L.V., Lapin V.A., Loginov A.B., Tumakov V.A., Korobkin A.V., Milyutina G.I., Samoilova O.S., Tikunova T.S., Pristupa A.S., Kondakova E.V., Domnikova N.P., Gavrilova L.V., Obidina N.A., Porokhina O.V., Rekhtman G.B., Mashchuk V.N., Khuazheva N.K., Kaporskaya T.S., Golubeva M.E., Maksimov A.G., Ploskikh M.A., Menshakova S.N., Maltsev V.I., Rossiyev V.A., Pilipenko G.I.


Aim. To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009. Materials and methods. The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009. The analysis excluded patients with acute promyelocytic leukemias who were recruited in the AML-92 and AML-95 studies. These patients' statutory forms adequately filled in were 60-70% therefore toxicity was analyzed on the basis of the data of 631 patients. Results. The baseline clinical and laboratory parameters in the patients enrolled in the studies in different years slightly differ in the count of leukocytes at the onset of the disease and in the level of lactate dehydrogenase (LDH): the recent studies revealed a larger number of high-risk group patients (leukocytes more than 30109/l; LDH more than 500 units) possibly due to the later diagnosis of AML. During the studies, the number of complete remissions remained as before (55%) after the first course and increased from 65 to 78% after the second course using cytosine arabinoside in high doses. Despite treatment intensification, mortality in the induction period remained as before (19-21%). Remission mortality decreased from 18 to 10-13%. The long-term results of using the aggressive therapy did not differ from those obtained during the standard treatment protocols. The duration of leucopenia after standard induction courses during the all studies remained equal (17-19 days); the exclusion was a HAM course as the second induction course after which the duration of neutropenia was much more than that of the standard course (17 and 10 days, respectively). During the study years, there was an increase in platelet transfusion volumes (from 20 to 53 doses during the first course and from 7 to 28 doses during the second course) and a reduction in the percentage of severe hemorrhagic complications. The incidence of pneumonias remained at the same level (40-50%) during the induction courses and that of septic complications and necrotic enteropathy considerably decreased from 40-46 to 17-19%. The incidence of invasive aspergillosis during the current programs from AML treatment was 10% (two induction courses), that of invasive candidiasis was 4.7% (two induction courses). Conclusion. The long-term results of treatment for AML were virtually unchanged regardless significant therapy intensification. Mortality remained high during induction treatment and in the postremission period. Its cause is severe infectious complications developing during myelotoxic agranulocytosis. The results of the analysis provide the basis for developing a new AML treatment protocol that should take into account all the merits and demerits of the previous protocols and provide a toxicity-treatment efficiency balance.
Terapevticheskii arkhiv. 2010;82(7):5-11
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Efficiency of the ALL-MB-2002 protocol in children with acute lymphoblastic leukemia

Rumyantseva Y.V., Karachunsky A.I., Aleinikova O.V., Fechina L.G., Shamardina A.V., Litvinov D.V., Ponomareva N.I., Boichenko E.G., Dudkin S.A., Streneva O.V., Kondratchik K.L., Mansurova E.G., Minkina L.M., Lapotentova E.S., Inyushkina E.V., Yudina N.B., Pavlova G.P., Zhukovskaya E.V., Khlebnikova O.P., Lagoiko S.N., Basharova E.V., Denisov R.E., Zlobina V.D., Banshchikova E.S., Aslanyan K.S., Kondakova E.V., Tselousova E.V., Myakova N.V., Turobova T.V., Ryskal O.V., Chipsanova N.F., Varfolomeyeva S.R., Rumyantsev A.G.


Aim. To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. Subjects and methods. A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. Results. With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73±13%; overall survival (OS) 78±2%; relapse-free survival 82±1%. The rates of EFS and OS were equal and amounted to 76±2 and 80±2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30±6 and 37±6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100109/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. Conclusion. Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.
Terapevticheskii arkhiv. 2010;82(7):11-19
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Recurrences of acute promyelocytic leukemia in children: experience with arsenic trioxide therapy and autologous hemopoietic cell transplantation

Baidildina D.D., Maschan M.A., Skorobogatova E.V., Dubrovina M.E., Rumyantseva Y.V., Maschan A.A., Rumyantsev A.G., Samochatova E.V.


Aim. To analyze the specific features of recurrences of acute promyelocytic leukemia (APL) in children after standard therapy with daunorubicin, cytosine arabinoside (Ara-C), all-trans retinoic acid (ATRA) and to develop further programmed treatment policy. Subjects and methods. The study included 9 patients with recurrent APL. The recurrences developed significantly more frequently in a very high-risk group (patients with minimal residual disease being preserved after the intensive therapy phase). Induction used arsenic trioxide (ATO) and/or standard chemotherapy + ATRA; ATO monotherapy was in consolidation. CD34+ cells were mobilized until molecular remission was achieved with high-dose Ara-C and granulocyte colony-stimulating factor. Pretransplantation conditioning involved melfalan as a basic drug in combination with high-dose Ara-C (5 pts), treosulfan (1 pt) or bisulfan (1 pt). Six patients received gemtusumab ozogamicin, 3-9 mg/m2, at different stages of therapy. Results. Before therapy one patient died; 8 patients achieved the second molecular remission; CD34+ cell mobilization and sampling were effective in 7 cases. Five patients were in long-term molecular remission after autologous hemopoietic stem cell transplantation (autoHSCT). Follow-up was 23-40 months. One patient is being prepared for transplantation. Following autoHSCT, another patient with a developed repeat recurrence died from complications due to related partially compatible transplantation. Visceral, including cardiological, toxicity of therapy was insignificant. In the APL-2003 protocol, overall and event-free survival rates were 93±3 and 76±6%, respectively. Conclusion. The application of ATO and autoHSCT in recurrent APL makes it possible to achieve and preserve the second molecular remission in case of insignificant extrahematological toxicity. Russian clinics should have access to ATO.
Terapevticheskii arkhiv. 2010;82(7):20-25
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Determinants for iron overload in patients with acute leukemias and aplastic anemia

Makeshova A.B., Levina A.A., Mamukova Y.I., Tsibulskaya M.M., Makarova P.M., Romanova E.A., Fevraleva I.S., Sudarikov A.B., Golovkina L.L., Stremoukhova A.G., Parovichnikova E.N., Savchenko V.G.


Aim. to reveal the determinants of the development of iron overload in patients with acute leukemias (AL) and aplastic anemia (AA). Subjects and methods. The investigation included 104 patients, including 64 with various types of AL, 31 with AA, and 9 with myelodysplastic syndromes (MDS). A group affiliation and an erythrocyte phenotype were determined from rhesus system antigens in all the patients and the HFE gene was studied to identify mutations. For control of siderosis, the authors determined serum iron (SI) by a colorimetric technique, by applying the kits of the AGAT firm (Russia), serum ferritin (SF) by an immunoradiometric method, by using the kits of Immunotech (Czechia). The volume of transfusion was estimated in the period of June 2007 to November 2009. Results. There is evidence for a relationship between the higher level of SF and the number of transfusions. SF was 1046.1 μg/l in patients, H63D heterozygous carriers who had received less than 10 packed red blood cell transfusions and 2856 μg/l in those who had 20 transfusions (p < 0.005). HFE gene mutation carriage accelerates iron accumulation and is an additional risk factor for siderosis. In patients with transfusion chimeras and a rare phenotype in terms of rhesus antigens, packed red blood cell transfusion results in a much more increase in iron stores. Conclusion. The most important factor of iron overload acceleration is no specific choice of packed red blood cells for patients with rare combinations of red blood cell antigens and for those with artificially induced chimeras.
Terapevticheskii arkhiv. 2010;82(7):26-29
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Prolonged bone marrow aplasias in patients with acute leukemias after chemotherapy

Gaidamaka N.V., Parovichnikova E.N., Zavalishina L.E., Garmayeva T.T., Gaponova T.V., Troitskaya V.V., Pokrovskaya O.S., Tikhomirov D.S., Khodunova E.E., Maryin D.S., Kaplanskaya I.B., Ustinova E.N., Mikhailova E.A., Isayev V.G., Gribanova E.O., Savchenko V.G.


Aim. To analyze the causes of prolonged hematopoietic tissue aplasias in patients with acute leukemias (AL) after chemotherapy courses. Materials and methods. Data on 7 patients with acute myeloid leukemia, followed up at the Hematology Departments, Hematology Research Center, Russian Academy of Medical Sciences, over the period 2003 to 2007, who had developed deep bone marrow aplasia (BMA) inadequate to cytostatic drug exposure during chemotherapy, were analyzed. The authors compared in all the patients the values of peripheral blood and bone marrow (BM) puncture specimens and the results of blood tests using the polymerase chain reaction at different AL development stages with the results of an immunohistochemical study using the markers of viruses of hepatitis C and B, a herpes group (EBV, CMV, HSV-1, HSV-2) and parvovirus B19. Results. The marker of hepatitis C was detected in 6 of the 7 patients with prolonged BMA; 3 of these 6 patients showed a simultaneous infection with hepatitis B. Six of the 7 patients were found to have concomitant BM lesion with various herpes group viruses. Two patients had a resistant form of AL. Conclusion. Hepatitis C virus infection in patients and the resistant form of the disease were the principal causes of the development of BMA inadequate to cytostatic drug exposure. Affliction of abundant bone marrow cells with herpes group viruses was not a direct cause, but might substantially aggravate BMA.
Terapevticheskii arkhiv. 2010;82(7):29-34
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Results of hemopoietic cell transplantation in the first complete remission in children with acute myeloid leukemia from an intermediate risk group

Dyshlevaya Z.M., Skorobogatova E.V., Maschan M.A., Shipitsyna I.P., Skvortsova Y.V., Trakhtman P.E., Balashov D.N., Pashko Y.V., Kurnikova E.E., Suntsova E.V., Goronkova O.V., Solopova G.G., Baidildina D.D., Kalinina I.I., Khachatryan L.A., Shneider M.M., Maschan A.A.


Aim. To analyze the results of allogeneic and autologous hemopoietic cell transplantations (allo- and auto-HCT) in children with acute myeloid leukemia (AML) from an intermediate risk group, most of which were performed using lower-intensity conditioning modes. Subjects and methods. The study enrolled 36 children from an intermediate risk group, who had undergone auto-HCT (n = 22) or allo-HCT (n = 14) in December 1994 to December 2008. The patients' age was 0.7 to 16.6 years (median 12.8 years). Chemotherapeutic conditioning regimens were applied to all the patients. Melphalan was a basic myeloablative agent in 83.3% of cases. Results. With a median follow-up of 4.6 years (1.1-13.8 years), three-year relapse-free survival (RFS) was 80.4%; overall survival (OS) was 65.6%. Recurrences were documented only in 6 (16.6%) patients from the auto-HCT. Transplantation-associated mortality (TAM) was 13.8% (five patients died). After allo-HCT versus auto-HCT, RFS, OS, and TAM were 100 and 68.7% (p = 0.03), 93.2 and 55.5% (p = 0.02), and 7.1 and 18.2%, respectively. Acute and chronic graft-versus-host reactions developed in 57.1 and 23.1%, respectively. Conclusion. Transplantation of allogeneic hemopoietic cells from a compatible related donor in the intermediate risk group children with AML, by using melphalan-based conditioning regimen, demonstrates a high survival rate with the minimum toxicity.
Terapevticheskii arkhiv. 2010;82(7):34-40
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Transplantation of the bone marrow from a HLA-compatible unrelated donor after immunoablative conditioning in children with acquired aplastic anemia unresponsive to combined immunosuppressive therapy: Preliminary results

Novichkova G.A., Maschan M.A., Shipitsyna I.P., Skvortsova Y.V., Persiantseva M.I., Lebedeva L.L., Bobrynina V.O., Baidildina D.D., Goronkova O.V., Solopova G.G., Khachatryan L.A., Petrova U.N., Suntsova E.V., Kalinina I.I., Sinitsyna V.V., Skorobogatova E.V., Balashov D.N., Dyshlevaya Z.M., Shelikhova L.N., Kurnikova E.E., Trakhtman P.E., Maschan A.A.


Aim. To analyze the efficiency of transplantation of the bone marrow from a HLA-compatible unrelated donor and continued immunosuppressive therapy (IST) in children with aplastic anemia (AA) unresponsive to 2 courses of IST. Subjects and methods. The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case. Results. Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors. Conclusion. The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15±11%.
Terapevticheskii arkhiv. 2010;82(7):41-47
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The use of allogeneic bone marrow transplantation and immunosuppressive therapy in the treatment of patients with acquired aplastic anemia

Ganapiyev A.A., Golubovskaya I.K., Zalyalov Y.R., Estrina M.A., Afanasyev B.V.


Aim. To evaluate the efficiency of related and unrelated allogeneic bone marrow transplantation (allo-BMT) versus immunosuppressive therapy (IST) in patients with aplastic anemia (AA) having no HLA-compatible bone marrow donor. Subjects and methods. The study covered 61 patients (34 men and 27 women) diagnosed as having acquired AA. Of them, 51 patients were diagnosed as having severe AA, 5 had supersevere AA, and 5 had non-severe AA. Combined IST (antithymocyte globulin (ATG) + cyclosporin A (CsA)) was used in 43 patients; allo-BMT was performed in 18. The basic types of ATG (ATGAM (Pfizer), thymoglobulin (Genzim), ATG (Fresenius), and goat antilymphocyte globulin (ALG) (Research Institute of Gerontology, Ministry of Health of the Russian Federation) were administered. CsA was given in a dose of 5 mg/kg/day. The standard conditioning regimen (ATGAM + cyclophosphanum) and fludarabine-containing (fludarabine + cyclophosphanum + ATG; busulfan + fludarabine + ATG) programs were used in the allo-BMT group. A combination of CsA and metothrexate was given to prevent a graft-versus-host reaction. Results. Among the IST-receiving patients, overall survival (OS) was 71%. After the first course of IST by follow-up month 6, the response rate was 74%. The second course of IST was performed in 7 patients unresponsive after the first-line IST and in 8 patients with recurrent AA. After the second course of IST, the response rate was 46.7%. Four patients who failed to achieve remission after 2 courses of IST received its third course. A complete response was obtained in 3 patients. In 18 patients following allo-BMT (related and unrelated), OS was 86%; event-free survival was 65. In 12 patients after related allo-BMT, OS was 91.7%. Conclusion. Related allo-BMT is the method of choice if there is a HLA-compatible sibling. If there are contraindications to it or no related donor, IST with ATG + CsA is indicated. Ineffective IST is an indication for unrelated allo-BMT that may be recommended as life-saving therapy for young patients under 40 years of age.
Terapevticheskii arkhiv. 2010;82(7):48-52
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The basic properties of bone marrow mesenchymal stromal cells from donors: superficial markers

Svinareva D.A., Shipunova I.N., Olshanskaya Y.V., Momotyuk K.S., Drize N.I., Savchenko V.G.


Aim. To characterize a superficial phenotype and to make a cytogenetic analysis of bone marrow (BM) mesenchymal stromal cells (MSC) from donors. Materials and methods. The study analyzed BM samples from 11 healthy donors. The phenotype of obtained MSC was analyzed using cytofluorometry. Chromosomal analysis was carried out at the first-second passage. Results. The superficial phenotype of MSC was steady-state during 8 passages and conformed to the worldwide standard for this cell population. The marker NGFR+ was detectable only during the first 2 passages and the count of CD146+ cells was decreased to 50% as consecutive passages were carried out, which confirms that MSCs have lost their neural and endothelial differentiation capacity. MSCs are stably able to differentiate only into the mesenchymal lineage. The detection of chromosomal rearrangements in MSCs at different stages of cultivation revealed no clonal rearrangements in any case. However, chromosomal aberrations were found 3-10% of metaphases at the first and second passages, which may be associated with chromosome instability in primary cultures. Conclusion. The pooled data suggest that the analyzed MSCs meet the conventional worldwide standards.
Terapevticheskii arkhiv. 2010;82(7):52-56
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Effectiveness of bortezomib and bortezomib-containing programs FOR the treatment of recurrent and resistant multiple myeloma

Mitina T.A., Golenkov A.K., Katayeva E.V., Lutskaya T.D., Trifonona E.V., Klinushkina E.F.


Aim. To evaluate the effectiveness of bortezomib and bortezomib-containing treatment programs in the therapy of resistant and recurrent multiple myeloma (MM) within a large unicenter study in real clinical practice conditions. Subjects and methods. The study enrolled 101 patients (48 men and 53 women aged 34 to 77 years, mean age 54 years) with resistant and recurrent MM. According to the types of paraprotein (PIg), the authors revealed the usual distribution: G, 60.7%; A, 23.8%; BJ, 13%; M, 1.15%; D, 1.15%. The PIg κ/λ light chain ratio was 1.7. The complicated course of the disease was noted in 50.4% of the patients. The patients were randomized into 4 treatment groups: V1 - velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 of a 21-day cycle; V2 - velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 20 mg orally on day 2 of a 28-day cycle; V3 - velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 9 mg/m2 orally for 4 days, prednisolone 60 mg/m2 orally for 4 days of a 42-day cycle; V4 - velcade 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, melphalan 9 mg/m2 orally for 4 days, prednisolone 60 mg/m2 orally for 4 days, cyclophosphanum, 250 mg/m2 intravenously dropwise on days 1 to 7 of a 60-day cycle. An average of 6.5 induction treatment cycles was performed. Results. Amongst the 27 patients receiving bortezomib therapy (V1), an objective response to therapy was obtained in 70.3%, including a complete response (CR) in 18.5%, a near-complete response (NCR) in 14.8%, and a partial response (PR) in 37%. When a combination of melphalan and bortezomib (VM; V2) was used, 22 patients achieved CR, NCR, and PR, which were equal to 9, 13, and 45.4%, respectively. In the group of 20 patients on the triple combination (VMP; V3), the amount of CR and PR was 90%. The use of the quadruple combination regimen (V4; VMCP) yielded an objective response (CR + NCR + PR) in 63.2% of the 32 patients, which did not virtually differ from other programs other than V3. However, the amount of CR +NCR (43.6%) was more than that in other groups. When all these programs were implemented, clinically significant myelotoxicity and grades 3 and 4 polyneuropathy were not seen. When the bortezomib-containing programs were applied, the median overall survival from the moment of diagnosis was 103 months. Conclusion. Bortezomib in the monotherapy and multidrug therapy for resistant and recurrent MM shows immediate and long-term benefits and a low toxicity.
Terapevticheskii arkhiv. 2010;82(7):57-61
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Diffuse large B-cell lymphoma with primary involvement of mediastinal lymph nodes: diagnosis and treatment

Mangasarova Y.K., Magomedova A.U., Kravchenko S.K., Zvonkov E.E., Kremenetskaya A.M., Vorobyev V.I., Maryin D.S., Gubkin A.V., Skidan N.I., Kaplanskaya I.B., Vorobyev I.A., Samoilova R.S., Vorobyev A.I.


Aim. To diagnose diffuse large B-cell lymphosarcoma (DLBCLS) with primary involvement of the mediastinal lymph nodes (LN) and to evaluate the efficiency of aggressive polychemotherapy (PCT). Subjects and methods. The study included 15 patients (6 men and 9 women aged 18 to 70 years; median 38 years) followed up at the Hematology Research Center, Russian Academy of Medical Sciences, in 2004 to 2009. Three and 12 patients had Stages II and IIE DLBCLS, respectively. B symptoms were found in 14 (93.4%) patients. Increased lactate dehydrogenase (LDH) concentrations were detectable in 14 (93.4%) patients; tumors of 10 cm or more (bulky disease) were seen in 11 (73.3%). Enlarged cervical, supraclavicular, and axillary lymph nodes were found in 9 (60%) patients; lung involvement via extension in 9 (60%), and invasion into the pericardium in 5 (33.3%) and soft tissues of the anterior thoracic wall in (13.3%). There were no signs of involvement of extranodal organs at the moment of diagnosis. All the 15 patients received PCT according to the modified NHL-BFM-90 program: 4 to 6 courses depending on the response to the therapy; 10 (66.6%) and 5 (33.3%) patients had 4 and 6 courses, respectively; for consolidating purpose, 11 (78.5%) patients were prescribed radiotherapy applied to the mediastinum in a cumulative dose of 36 Gy due to the fact that they had a residual mass. Results. Thirteen (86.6%) patients achieved a complete remission (CR). Primary PCT resistance was confirmed in one case. Another patient was stated to have near-complete remission. No recurrences were notified during the follow-up. The mean CR duration was 24.5 (range 2-49) months. Conclusion. DLBCLS with primary LN involvement is an individual nosological entity to be differentiated from primary mediastinal large B-cell lymphosarcoma. In most cases, DLBCLS shows signs of a poor prognosis, which makes it necessary to perform aggressive PCT.
Terapevticheskii arkhiv. 2010;82(7):61-65
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Polyclonal rabbit antithymocyte globulin (thymoglobulin): immunomodulatory effects and new aspects of its clinical application

Kulagin A.D., Lisukov I.A., Miloserdov I.A., Afanasyev B.V.


Antithymocyte immunoglobulins remain to be one of the most effective immunosuppressants used in transplantology and in the treatment of autoimmune diseases. The unique features of the mechanisms of individual antithymocyte globulin preparations should be borne in mind. Due to its polyclonal nature, thymoglobulin provides a wide spectrum of diverse immunomodulatory effects, which is the basis for its wide use in order to reduce the risk for graft rejection and a graft-versus-host reaction and to treat aplastic anemia.
Terapevticheskii arkhiv. 2010;82(7):65-72
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Hereditary spherocytic hemolytic anemia in an adult with the formation of ectopic foci of extramedullary hemopoiesis in the chest

Melikyan A.L., Egorova E.K., Karagyulyan S.R., Silayev M.A., Kaplanskaya I.B., Gitis M.K., Kolodei S.V., Kovaleva L.G.


The paper describes a rare case of formation of paravertebral extramedullary hemopoietic foci in microspherocytic anemia or Minkovsky-Shoffar disease in an adult. Therapeutic splenectomy has led to regression of extramedullary hemopoietic foci, which supports that there is a direct relationship of the above formations to the specific features of the etiology and pathogenesis of microspherocytic anemia.
Terapevticheskii arkhiv. 2010;82(7):72-75
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Multiple myeloma in renal transplant recipients

Rekhtina I.G., Biryukova L.S., Varshavsky V.A., Golitsina G.P., Savchenko V.G.


Severe renal failure (RF) may be the first and only clinical manifestation of multiple myeloma (MM). Occasionally the disease remains long unrecognized and the patients receive renal function replacement therapy, including renal transplantation (RT). To treat MM in renal transplant recipients is a complex medical and ethical problem. The paper presents the authors' experience in treating 3 patients with MM diagnosed after RT and evolving transplant lesion. Various morphological types of grafted kidney lesion were detected. These included fibrillar glomerulonephritis, cast nephropathy, and the latter concurrent with light-chain deposition disease. RF most rapidly progressed in cast nephropathy. The natural history of the disease was unfavorable in all patients; VAD and PAD chemotherapy programs proved to be ineffective. It is concluded that RT should not be performed in patients with extended-stage MM due to the fact that there is a considerable risk for renal transplant lesion and severe infectious complications that may occur during chemotherapy. Blood and urine immunochemical studies should be conducted in all the patients who are to undergo RT.
Terapevticheskii arkhiv. 2010;82(7):76-79
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Neurosurgical treatment for chronic subdural hematoma in a patient with chronic autoimmune thrombocytopenic purpura

Ryzhko V.V., Mamonov V.E., Shutov S.A., Klodzinsky A.A.


Intracranial hemorrhage in patients with chronic autoimmune thrombocytopenic purpura (CATP) is a rare and severe complication of the disease. By taking into account a concomitance of chronic subdural hematoma (CSH) and CATP and no generally accepted approaches to managing the patients with this concomitance, the authors describe a clinical case of mini-invasive CSH drainage in a patient with CATP.
Terapevticheskii arkhiv. 2010;82(7):79-81
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