[Long-term results of treatment for T-cell lymphoblastic lymphomas].

AIM: To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL). SUBJECTS AND METHODS: Twenty-five patients with a verified diagnosis of T-LBL were examined. Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a preponderance of patients with the generalized stages of the diseases: 2, 5, and 18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20 (80%) of the 25 patients. Their treatment was performed according to the GMALL 2002 program and similar CHOP courses. Analysis was made in 2 groups that were not different in their clinical and morphological characteristics. Group 1 consisted of 17 of the 25 patients treated according to the GMALL programs; Group 2 comprised 8 patients who had similar CHOP and other chemotherapy regimens. RESULTS: In Group 1, 15 (88%) patients achieved a complete clinical and hematological remission and 2 (12%) patients died in the first stages of the treatment. No relapses were noted. The median survival had not been achieved; 5-year overall survival was 88 +/- 8%. In Group 2, three patients were alive; 2 completed their treatment; 5 (63%) patients died from treatment failures. The median survival was 23 +/- 18%; 5-year overall survival was 45%. CONCLUSION: The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

[High-dose polychemotherapy of patients with poor-prognosis anaplastic T.0-large cell ALK+ lymphosarcoma].

AIM: To evaluate efficacy of the protocol NHL BFM-90 in the treatment of adult anaplastic large cell lymphosarcoma (ALCL) ALK+ and validity of addition of transplantation of autologous stem hemopoietic cells (ASHC) into first line treatment. MATERIAL AND METHODS: We treated 13 patients with stage III-IV ALCL ALK+. The age of the patients ranged from 17 to 44 years (median 26 years). The diagnosis was made using morphological, histological, immunohistochemical methods with application of monoclonal antibodies to CD30, ALK, CD3, CD4, CD8, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA. The patients were treated according to the protocol NHL BFM-90. ASHC was made in two patients with the disease stage IV. RESULTS: We obtained a complete remission in 12 of 13 patients, one woman died of infectious complications in the beginning of the treatment, one man had early recurrence 45 days after the end of the treatment with lethal outcome and disease progression. Two patients at stage IV and poor prognosis had undergone ASHC transplantation. They are now in remission for 5 and 12 months. CONCLUSION: ALCL ALK+ is characterized by an aggressive clinical course (11 of 13 patients had stage III-IV), high rate of extranodal lesions. Twelve patients achieved a complete remission, 11 (91.6%) of 12 patients are alive in observation median 27 months. We effectively used ASHC transplantation in the first-line treatment of 2 patients with stage IV of the disease and poor prognosis.

[Diagnosis and treatment of skin T-cell lymphoma undergoing transformation in lymphosarcoma].

AIM: To define complex of parameters characterizing transformation of skin T-cell tumors in lymphosarcoma; to show specific treatment of patients with this transformation. MATERIAL AND METHODS: Of 57 patients with primary T-cell lymphomas of the skin (mycosis fungoides, Sezary's disease), we studied 12 patients with transformation of the process into lymphosarcoma by clinical, histological, moleculobiological and immunophenotypical parameters. RESULTS: We found that transformation of T-cell lymphoma into lymphosarcoma occurred in different time from the disease onset (2-12 years). In patients with mycosis fungoides (MF) the transformation was local while in those with Sezary's disease (SD) transformation of the tumor clone was determined by appearance of peripheral blood tumor cells rejuvenation. Morphological alterations were accompanied with immunomorphological parameters of progression. Most significant of them were high expression of the proliferative activity marker Ki-67 (10-70%), enhancement of activation (CD30, CD25), loss of some linear T-cell markers. Treatment of lymphosarcoma arising on the background of lingering MF or SD may combine two types of antitumor treatment--intensive and supporting because of coexistence of different clones of one tumor. CONCLUSION: Verification of skin T-cell lymphoma diagnosis and its transformation into lymphosarcoma must be based on the evidence from a number of examinations: histological, immunophenotyping, moleculobiological and clinical. Among criteria of the transformation, markers of lymphoproliferative activation are of great importance.

[Efficacy of therapy of different variants of anaplastic large T-cell lymphomas].

AIM: To compare efficacy of NHL-BFM-90 and CHOP-like courses in the treatment of anaplastic large cell lymphoma (ALCL). MATERIAL AND METHODS: Twenty-two patients with ALCL participated in the study. The diagnosis was made basing on the findings of clinical, device, morphological, immunohistochemical and molecular-genetic examinations with application of a panel of monoclonal antibodies to CD30, ALK, CD3, CD4, CDS, CD7, CD34, CD15, CD68, CD20, CD45RO, CD45RA, Ki-67. 14 cases of 22 were negative by kinase of anaplastic lymphocytes (ALK-) and 8 were positive (ALK+). Mean age of ALK-ALCL patients was 39.6 +/- 4.1 years, of ALK+ALCL patients - 23.4 +/- 2.6 years. 14 patients were treated by the protocol NHL-BFM-90, 8 were initially treated with other schemes (CHOP, MACOP-B, BEACOPP and others). All 14 patients treated according to NHL-BFM-90 had ALCL stages III-IV with B-symptoms. 12 patients who completed treatment by the above protocol achieved complete remission after the forth course, 2 patients failed the treatment. Of 8 ALCL patients treated initially according to other schemes, a complete remission was achieved in 4 patients (2 had stage II). One of 4 patients with remission had recurrence. Four patients who had failed to achieve complete remission died of the disease progression. CONCLUSION: ALCL occurs more frequently in young and middle-aged patients. The disease has an aggressive course with rapid generalization. For such processes it is more preferable to use a modified protocol NHL-BFM-90.

[Determination of T-cell clonicity by a T-cell receptor gamma-chain: final data].

AIM: To test diagnostic efficacy of T-cell clonicity determination by a gamma-chain of T-cell receptor (TCR). MATERIAL AND METHODS: The examination covered 426 patients (458 tests). T-cell tumors were detected in 132 patients. The samples from 294 patients in whom T-cell tumors were not found were referred to the laboratory for a differential diagnosis. Clonicity was determined by gamma-chain of TCR in the test for conformation polymorphism of one-chain DNA fragments. All the tests were made in one laboratory. RESULTS: Sensitivity of the method, found by analysis of different delusions of the cell line Jurkat in selected polyclonal CD3+ cells is 10%. The results were of 3 kinds: clonal, doubtful and polyclonal. In patients free of T-cell tumors there were 15 (5%), 34 (11%) and 258 (84%) false positive, doubtful and true negative results. False positive results were most frequent in an acute phase of infectious mononucleosis--in 8 (33%) of 24 patients. 127 (84%) true positive, 5 (3%) doubtful and 19 (13% 0 false negative results were documented in patients with T-cell lymphoma. The occurrence of false negative results was the highest in anaplastic CD30+ T-cell lymphomas--in 6 (46%) of 13 cases. CONCLUSION: Diagnostic efficacy of the method is 92%, but in 10% the result is doubtful. Main reason of false negative results is a small number of tumor cells in tissue samples. The main reason of false positive results is prevalence of one or some T-cell clones in the presence of immune response caused by viruses, autoimmune diseases and, possibly, depletion of bone marrow in aplastic syndromes.

[Clinicomorphological characteristics of Sezary's disease and mycosis fungoides].

AIM: To try a combined approach to the study of clinicomorphological and immunophenotypical characteristics of primary cutaneous T-cell lymphomas. MATERIAL AND METHODS: Clinical, histological, genotypic and immunophenotypical parameters were studied in 7 patients (4 male and 3 female, mean age 53.1 +/- 7.8%) with Sezary's disease (SD) and 10 patients (6 male, 4 female, mean age 54.0 +/- 4.0 years) with mycosis fungoides (MF) treated in Hematological Research Center in 1998-2004. RESULTS: Six of seven SD patients had SD stage IV with leukemization, Sezary's cells were found in peripheral blood. Bone marrow and lymph nodes involvement was observed in 5 patients. Morphological signs of transformation into lymphosarcoma were detected in three patients. Skin samples of all the patients showed epidermotropism with lymphoid infiltration of the derma and skin appendages. All the patients had clonal rearrangement of T-cell receptor by gamma-chain. Immunophenotyping (IPT) detected T-cell markers CD45RO, CD43, CD3, CD4 on lymphoid cells. IPT of peripheral blood lymphoid cells was typical for SD in 3 patients. Low density of CD4 and CD2, CD4 and CD5, the presence of CD7 were registered in 1 patient each. The disease history was 3.4 +/- 0.7 years. A lethal outcome was related with septic complications after polychemotherapy. MF history in 10 patients was 10.9 +/- 2.1 years. Stages III and IV were diagnosed in 2 of 10 patients. All the patients had typical pathohistological changes. Polymerase chain reaction test detected clone by rearrangement of gamma-chain of T-cell receptor. In 2 patients IPT detected CD4 absence in the presence of CD8 and CD7. The aberrant clone typical for NK-cells was detected in one case. Two patients died of the disease progression after 7 and 20 years of MF. CONCLUSION: Multiple tests help early diagnosis and conduction of optimal therapy for cutaneous T-cell lymphomas.

[Characteristics of a clinical course of immune cytopenias with a high titer of autoantibodies to the microsomal antigen of the thyroid gland]. / Osobennosti klinicheskogo techeniia immunnykh tsitopenii, soprovozhdaiushchikhsia povyshennym titrom autoantitel k mikrosomal'nomu antigenu shchitovidnoi zhelezy.

AIM: To ascertain the role of high antibodies (Ab) titers to microsomal antigen (MA) of the thyroid in clinical manifestations of cytopenic syndromes. MATERIAL AND METHODS: Clinical data are presented on 144 patients with depressed hemopoiesis having different levels of thyroid Aab. RESULTS: When the titer was significantly elevated (41% patients with immune cytopenias), hematological malignancies run with recurrences, remission is rare. Treatment of the thyroid pathology improves hematological indices in some cases though does not reduce titers of Ab thyroid MA. CONCLUSION: Detection of autoimmune pathology of the thyroid is necessary not only for specification of the concurrent process diagnosis but also for initiation of adequate combined treatment.

[T-cell tumors with aplastic syndromes]. / T-kletochnye opukholi, protekaiushchie s aplasticheskimi sindromami.

AIM: To detect and verify the existence of a specific form of T-cell tumor accompanied by isolated lesions of bone marrow and aplastic syndromes. MATERIAL AND METHODS: Four patients with aplastic syndromes were examined using clinical, histological, cytological, cytogenetic, and immunophenotypic methods. RESULTS: Four cases of T-cell tumors of bone marrow with clinical and morphological manifestations of aplastic syndrome and scanty proliferation activity in bone marrow alone were diagnosed. The proliferation activity in bone marrow was observed as formation of small clusters composed of small-size lymphoid cells with dense nucleus. Dynamic monitoring of two patients revealed a trend toward an increase in the lymphoproliferation base against the remaining clinical picture of aplastic syndrome. The T-cell immunophenotype characterized by disappearance of some markers or decrease in their density, was observed only in some blood and bone marrow lymphocytes. The most significant changes of immunophenotype were observed in one of the patients (CD2+CD3-CD4-CD5-CD7-CD8-CD16-CD56-CD45RO++). The same patient had pronounced cytogenetic changes (47XY+Y[8], 47, XY, del(1)(p10) [23], 46 XY [3]) and resistance to routine therapy, including cyclosporin. In one patient the process transformed into lymphosarcoma. CONCLUSION: The results obtained in four patients allow their clinicomorphological characteristics to be regarded as particular forms of T-cell tumors accompanied by bone marrow damage and aplastic syndrome.

[Use of polymerase chain reaction for determining T-cell clonality]. / Opyt ispol'zovaniia polimeraznoi tsepnoi reaktsii dlia opredeleniia T-kletochnoi klonal'nosti.

AIM: To distinguish T-cell lymphomas and reactive T-cell proliferation it is important to confirm the ability of T-cells to be cloned. Conventional histological and immunophenotypic methods fail to determine the ability of T-cells to be cloned. An experience in the use of detection of T-cell receptor gene gamma-chain (TCRy) rearrangement for determining T-cellular clonality is described. MATERIAL AND METHODS: Polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) were used to determine T-cell clonality. Twenty healthy donors, 28 patients with T-lymphomas, and 26 patients with various non-T-cell lymphoproliferative disorders or reactive processes were studied. RESULTS: T-cell monoclonality was detected in 23/28 (82%) T-cell lymphoma cases, whereas in all the samples from normal subjects a polyclonal pattern of rearrangements TCRy was found. The sensitivity of the method was estimated as 2.5%, 7%, and 10% was demonstrated for bone marrow, spleen, and peripheral blood, respectively. CONCLUSION: PCR-SSCP for TCRy was found to be a useful supplement to routine histological and immunophenotypic methods in the diagnosis of T-cell lymphomas.

[Autoantibodies to the thyroid gland in hemoblastoses and cytopenias]. / Autoantitela k shchitovidnoi zheleze pri gemoblastozakh i tsitopeniiakh.

AIM: To study the level of thyroid antibodies (TAB) in blood diseases. MATERIAL AND METHODS: TAB levels dynamics was studied in 413 patients with hematological diseases. RESULTS: Increased incidence of cases with high Ab titer to thyroid microsomal antigen was found. High and moderate titers were revealed in 33% of all examinees, including 41%, 22%, 32% and 29% among patients with immune cytopenia, chronic lymphoid leukemia, generalized mature-cell lymphoma and myeloproliferative diseases, respectively. These high and moderate titers were rather stable. In 15% patients Ab were elevated insignificantly, this rise being unstable. CONCLUSION: Stable high titers of antibodies to thyroid antigens point to increased incidence rates of concomitant autoimmune hyroiditis in patients with blood diseases.

[Use of thymodepressin for treating autoimmune cytopenia]. / Primenenie timodepressinoa dlia lecheniia autoimmunnykh tsitopenii.

AIM: To study influence of thymodepressin on the course of autoimmune cytopenia. MATERIAL AND METHODS: Thymodepressin is a new synthetic hemoregulatory dipeptide (gamma-D-Glu-D-Trp). It was used for the treatment of 22 patients with autoimmune cytopenia. RESULTS: Hemoglobin levels were elevated in autoimmune hemolytic anemia and platelet levels were high in idiopathic thrombocytopenic purpura. A thymodepressin course resulted in a fall of total lymphocyte count and activated CD3+CD69+ lymphocytes. CONCLUSION: The above results, safety, absence of toxicity and allergenicity, parenteral and intranasal useability open perspectives for further studies of therapeutic action of thymodepressin as an immunodepressant in autoimmune processes.

[Postradiation recovery of hematopoiesis in mice affected by Neogen (IEW)]. / Postradiatsionnoe vosstanovlenie krovetvoreniia u myshei pod vliianiem neogena (IEW).

The effect of the synthetic peptide IEW (Neogen) with immunomodulating properties on postradiation recovery of haemopoiesis was investigated. We have shown that Neogen is a potential stimulator of haemopoiesis. The administration of Neogen after irradiation shortened duration of period of the recovery of the compartment of CFU-S-8 and the amount of bone marrow cells. The comparision of the effects of Neogen and GM-CSF (Leucomax) and G-CSF (Granocyte 34) have shown that the targets for these agents are probably different: polypotent CFU-S-for Neogen, and CFU-GM-for GM-CFS. Based on the results, we suggested the mechanism of Neogen effects on heamopoiesis.

[Radiation damage of the thyroid gland as a probable cause of increased incidence of non-Hodgkin lymphoma and other hematologic diseases]. / Radiatsionnoe povrezhdenie shchitovidnoi zhelezy kak veroiatnaia prichina uvelicheniia chastoty nekhodzhkinskikh limfom i drugikh gematologicheskikh zabolevanii.

Th distribution of autoimmune thyroiditis in the patients with diseases of blood system was investigate. The attribute of autoimmune thyroiditis was revealed by the detection of antimicrosomal antibodies. It was established that the autoimmune thyroiditis are more often in patients with various hematological diseases than in control group. It is supposed that the increase in frequency of some hematological diseases in residents suffered from the Chernobyl accident can be defined not only by the influence of the radiation on blood system, but also can be connected with damage to thyroid glands.

[The probable sequelae of thyroid damage from radioactive iodine during the Chernobyl accident]. / Veroiatnye posledstviia povrezhdeniia radioaktivnym iodom shchitovidnoi zhelezy v period Chernobyl'skoi avarii.

An important peculiarity of the Chernobyl catastrophe is the discharge into the atmosphere of tremendous amount of radioactive iodine and, as a result, selective damage of the thyroid in children from the affected areas. The most dangerous consequence is the thyroid cancer. The analysis of the situation when children's thyroids were subjected to irradiation shows that tumors can most frequently develop as late as 20-30 years after irradiation. There are reasons to believe that tumors are induced by low dose of irradiation. The most important factor in development of pathologies is for sure the age of the children of the moment of irradiation. A well-known consequence of the impact of radiation on the thyroid is the lymphocyte thyroiditis. The interest to this pathology is determined by the fact that it substantially increases the probability of development of various haematologic diseases (lympho- and myeloproliferative neoplasms).