[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.

[Ten-year outcomes of lymphogranulomatosis treatment according to the protocol MOPP-ABVD+radiotherapy].

AIM: To analyse overall recurrence-free survival of lymphogranulomatosis (LGM) patients given polychemotherapy (PCT) MOPP (mustargen-caryolisin, vincristine, natulan, prednisolone) - ABVD (adriamycin, bleomycin, vinblastin, dacarbasin) in combination with radiotherapy (RT) for 10 years. MATERIAL AND METHODS: The trial included 211 LGM patients admitted to Hematological Research Center in 1990-1996 from other hospitals without random selection. The patients were examined by the standard program including biopsy of the affected organ or lymph node, bilateral trephine biopsy. Splenectomy was performed in 17 patients, 83 patients received PCT in other hospitals, 128 untreated patients received MOPP-ABVD therapy (3 courses of MOPP and 3 courses of ABVD). Forty one patients had defects in PCT, 16 of them rejected PCT and RT. The latter was performed 4 weeks after the 6th course, contraceptives were not prescribed to women. At LGM stage II-III RT was performed by the subradical program (no radiation to ilioinguinal lymph nodes) in doses 40-44 Gy on the foci and 32-36 Gy preventively, on massive and residual foci after PCT - 5-10 Gy additionally. RESULTS: Ten-year overall and recurrence-free survival in the untreated group reached 83 and 80%, respectively, for pretreated patients - 46 and 36%, respectively. Causes of death of 26 patients were LGM progression, infection (tuberculosis, as a rule), secondary tumors and acute myeloblastic leukemia (AML). After remission 25 women gave birth to a healthy child and 12 healthy children were born to 9 males. CONCLUSION: MOPP-ABVD plus radiotherapy program according to subradical and radical variants was in the past effective but invalidating rescue therapy. Present-day programs consider the histological variant, stage and prognostic factors allowing an individual therapeutic approach with step-by-step reduction of RT in the treatment of LGM patients. Involvement of the bone marrow in primary patients had no influence on the treatment results. This refers this affection not to a generalized stage IV, but to stage III along with involvement of the lymph nodes and the spleen.

[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.

[Hemoglobin oxygen-transport activity in lymphosarcomas]. / Kislorodtransportnaia aktivnost' gemoglobina pri limfosarkomakh.

To evaluate oxygen transport function of Hb in lymphoid sarcomas, 15 patients aged 16-63 were examined for Hb oxygen capacity, concentrations of fetal Hb and creatinin, basic ligands H+, CO2, 2,3-diphosphoglycerate (2,3-DPG). Oxy-Hb dissociation curves were plotted. The patients' blood contained HbF in elevated quantities, whereas red cells had high creatinin. This emphasizes the role of hemolysis in genesis of anemia in lymphosarcomas. 70% of the examinees retained normal Hb affinity to oxygen in vivo, in 30% this affinity exceeded the standard. Compensatory mechanism responsible for low Hb affinity to oxygen in this disease fails. Therefore lymphosarcoma patients with anemia need early replacement hemotransfusions.

[The first case of Hb Camden carriage in Russia]. / Pervyi sluchai nositel'stva Hb Camden v Rossii.

Structural hemoglobinopathy due to carriage of Hb Camden was diagnosed in a male patient and his mother. Anomalous Hb was detected after a detailed analysis of the clinical evidence, blood smears microscopy, marrow examination, data obtained by a complex of methods to identify unstable Hb. It was defined as Hb Camden beta 131 GLN-->GLU. The carriage of this variant brings no clinical manifestations, but leads to impaired red cells morphology, decline of their life span, enhanced hemolysis. These properties are typical for mutant Hb lacking stability. Hb Camden carriage is considered as a compensatory hemolytic process.

[Distribution of abnormal hemoglobins S and C in the Republic of Guinea]. / Rasprostranenie anomal'nykh gemoglobinov S i C v Gvineiskoi respublike.

Distribution of the HbS and HbC in the Guinean Republic was determined by the analysis of the excerption of 2213 inhabitants representing different ethnic groups of the country. It was found that the mean frequency of the HbS heterozygotes is 21.2 +/- 0.9% and of the HbC heterozygotes is 2.6 +/- 0.3%. Among major nationalities of the country the frequencies of the HbS heterozygotes make up 21.0 +/- 1.9% for the Fulbe, 22.2 +/- 1.6% for the Malinke and 26.5 +/- 1.6% for the Susu and frequencies of the HbC heterozygotes make up 3.0 +/- 0.8% for the Fulbe, 2.5 +/- 0.6% for the Malinke and 1.6 +/- 0.4% for the Susu. Relative viability of the HbS and HbC carriers for major Guinean nationalities is estimated. The relative fitnesses account is 1.05-1.13 for HbC heterozygotes and 1.07-1.16 for HbC heterozygotes.

[A new strategy for structural identification of abnormal human hemoglobins]. / Novaia strategiia strukturnoi identifikatsii anomal'nykh gemoglobinov cheloveka.

A new strategy for structural identification of abnormal human hemoglobins is proposed. It is based on micropreparative modification of electrophoretic separation of globins on Cellogel strips with subsequent quantitative isolation of a pure, desalted globin chain, in a form suitable for its subsequent structural investigation. Among the major advantages of the new strategy age possibility to use small blood samples (0.1-0.2 ml), short analysis time, relative simplicity and low cost.

Micropreparative electrophoresis of globin chains on cellulose acetate film in structural identification of abnormal human hemoglobins.

A simple and rapid micropreparative method for isolating 5 to 30 nmol of globin chain, followed by structural identification of abnormal human hemoglobins, is described. The method is based on the electrophoretic separation of globins on ordinary Cellogel films under denaturating conditions with subsequent cutting out of the protein zones and solubilization of Cellogel and the electrophoretic buffer components in a specially selected solvent in which the globin chain undergoes quantitative precipitation. The method makes it possible to simplify and speed up the structural identification of commonly occurring abnormal hemoglobins. The advantages and limitations of the method are discussed along with its potential uses in structural protein chemistry.

[Micropreparative thin-layer peptide maps in the molecular diagnosis of abnormal human hemoglobins]. / Mikropreparativnye tonkosloinye peptidnye karty v molekuliarnoi diagnostike anomal'nykh gemoglobinov cheloveka.

General factors determining the possibility of application of peptide maps in thin layer of microcrystalline cellulose as a micropreparative method in molecular diagnostics of abnormal hemoglobins were studied. The effects of absorbtional capacity of cellulose and amino acid impurities in it, choice of eluent and elution technique, peptide structure and extent of its modification in staining as well as completeness and specificity of globin chain enzymatic digestion on peptides extraction from thin layer were analysed. The results of structural identification of Hb D Punjab beta 121 Glu----Gln at a Cypriot; Hb O Arab; beta 121 Glu----Lys at a Bulgarian woman, living in Kalinin region (the second case in the USSR); Hb M Saskatoon beta 63 His----Tyr at a woman from Georgia (the second case in the USSR); Hb Buenos Aires beta 85 Phe----Ser at a Russian girl (the first case in the USSR and the third case in the world); Hb Dagestan alpha 60 Lys----Glu at two members of a Lesgin family from Dagestan; Hb Agenogi beta 90 Glu----Lys at a Hungarian woman; Hb Setif alpha 94 Asp----Tyr at three patients from Cyprus and Hb Detroit beta 95 Lys----Asn at an Azerbaijanian woman (the first case in the USSR and the second case in the world) are presented.