[Transplantations of allogenic and autologous hemopoietic stem cells in acute leukemia (results of 20-year experience)].

AIM: To analyse results of transplantation of allogenic and autologous hemopoietic stem cells (allo-THSC and auto-THSC) with myeloablation preconditioning in patients with acute leukemia (AL) performed in 1987-2006. MATERIAL AND METHODS: A total of 71 allogenic and 45 autologous THSC were performed in 116 patients with different AL variants. Conditioning in all allo-THSC included busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). This regimen was used in 29 recipients of auto-HSC. Cyclophosphamide in a dose 120 mg/kg and total radiation of the body in a dose 12 Gy were given to 16 recipients. Overall, relapse-free and event-free survival of patients after THSC were analysed as well as early (first 100 days) and overall lethality. Auto-THSC in 15 patients was for the first time followed by immunomodulating therapy aimed at prevention of AL relapses: in acute myeloid leukemia ATRA in combination with alpha-interferon, in acute lymphoblastic leukemia (ALL)--ronkoleukin, interleukin-2 preparation. RESULTS: Overall survival of AL patients after allo-THSC for the observation period increased from 31 to 58%, early lethality fell from 44 to 4%. Results of allo-THSC conducted in the first complete remission were much better than in patients with other AL stages at the time of THSC. After auto-THSC 5-year survival rose from 22 to 60% while early lethality reduced from 33 to 4%. Administration of immunomodulating therapy after auto-THSC increases 5-year survival from 35 to 80%. CONCLUSION: Outcomes of THSC in AL has improved for the last 20 years. Outcomes of allo-THSC performed in the first complete remission are much higher. Immunomodulating therapy after auto-THSC promoted better results.

[Allogenic transplantation of hemopoietic stem cells in low-intensity regimes in patients with hematological malignancies].

AIM: To test feasibility of transplantation of hemopoietic stem cells (THSC) with conditioning in low-intensity regimen associated with minimal toxic complications and engraftment in patients with hematological malignancy (HM) from a high risk group. MATERIAL AND METHODS: THSC was performed in 33 patients aged 18 to 65 years. Most of the patients suffered from acute leukemia and advanced forms of myelodysplastic syndrome. All the patients had severe complications excluding standard transplantation. Pretransplantation preparation was based on fludarabine and moderate doses of busulfane. Engraftment was achieved in 94% patients. Of complications, there were primarily infections, relapses, graft versus host reactions (45, 24, 57.5%, respectively). Overall survival was 53%, relapse-free--67%, follow-up median 23.6 months. CONCLUSION: THSC after conditioning in the regime of low intensity is an effective method of HM treatment in patients with contraindications to standard transplantation. The main problem is a high risk to develop graft versus host reaction, especially a chronic form.

[Allogenic bone marrow transplantation in chronic myeloid leukemias]. / Transplantatsiia allogennogo kostnogo mozga pri khronicheskom mieloleikoze.

AIM: To assess the role of allogenic bone marrow (ABM) transplantation in chronic myeloid leukemia (CML). MATERIAL AND METHODS: 44 ABM transplantations were performed in 37 CML patients in the chronic phase and 7 patients in acceleration or blast crisis. RESULTS: A complete molecular remission was achieved in 26 (59%) patients: 67.6% after ABM transplantation in the chronic phase and only 14.3% after myelotransplantation in non-chronic phase. Follow-up was 8-150 months (median--59 months). Early lethality after ABM transplantation in the chronic phase was under 14%. A phase of the disease plays a key role in ABM transplantation. If it is made in a chronic phase, CML recurrence rate is low (in our series it was 14%), efficacy of donor's bone marrow lymphocyte transfusions is high. The second complete molecular remission was achieved in 3 of 4 cases of posttransplantation recurrences. Probability of maintenance of a complete remission after ABM transplantation in a chronic phase was 75%, recurrence-free survival--64%, uneventful survival 55% for 90 months. CONCLUSION: The experience of many years demonstrates high efficacy of ABM transplantation in the treatment of chronic myeloid leukemia. It promotes long-term molecular remission the maintenance of which did not require therapy in 65% patients.

[Allogenic bone marrow transplantation after reduced intensity conditioning regimens in therapy of patients with hemoblastoses]. / Allogennaia transplantatsiia kostnogo mozga posle rezhimov konditsionirovaniia ponizhennoi intensivnosti v terapii bol'nykh gemoblastozami.

AIM: To investigate effectiveness of allogenic transplantation of the bone marrow (TBM) in the treatment of hemoblastosis patients from a high risk group, the course of donor bone marrow retention, tolerance and antitumor activity of this therapy. MATERIAL AND METHODS: 11 patients received TBM in low-intensity regimen in Hematological Research Center in 1999-2001. All the patients were from a high risk group. Conditioning was based on the combination of fludarabin with busulfan. The transplanted precursor cells were taken from the bone marrow and/or peripheral donor blood. The retention was controlled by differential agglutination of erythrocytes and amplification of hypervariable sites of DNA. Minimal residual disease was controlled by standard cytogenetical tests, fluorescent in situ hybridization or reverse-transcriptase polymerase chain reaction. RESULTS: All the patients tolerated pretransplantation conditioning well. By chimerism, signs of retention of donor bone marrow on day +30 after TBM were observed in 9 patients of 11. Acute graft versus host reaction developed in 5 patients. This reaction was treated conventionally with methylprednisone and cyclosporin A, in 4 cases with a good effect. A complete remission persists in 5 patients. Mean follow-up lasted for 241 days. CONCLUSION: Thus, transplantation was successful in 50% patients with an unfavourable prognosis who are still in a complete remission. This suggests efficacy of the above method of treatment.

[Dystrophin gene expression in patients with Duchenne muscular dystrophy after myoblast transplantation]. / Ekspressiia gena distrofina u bol'nykh miodistrofiei Diushenna posle transplantatsii mioblastov.

Based on originally designed technique of myoblast cultivation and in accordance with the approved by the Russian Ministry of Health "one muscle treatment" protocol of myoblast transplantation to the Duchenne muscular dystrophy patients, the first in Russia clinical trial of this gene correction method was carried out. Immonologically related myoblast cultures (30 to 90 million cells per patient) were injected after all preliminary procedures into tibialis anterior muscles of four boys selected from a group of volunteer recipients (Duchenne muscular dystrophy patients) based on the analysis of a number of surface antigens in donor-recipient pairs. The condition of the patients remained satisfactory during the whole period of post-transplantation follow-up (from 6 months to 1.5 years). Six months after myoblast transplantation the presence of donor DNA or dystrophin synthesis was demonstrated in muscle biopsies of three out of four patients. This result confirms efficacy and safety of the procedure used.

[HLA-antigens and some pathogenetic aspects of reactive arthritis]. / HLA-antigeny i nekotorye patogeneticheskie aspekty reaktivnykh artritov.

AIM: Investigation of associations of reactive arthritis (ReA) with histocompatibility antigens class I and II and determination of new approaches to assessment of association ReA with antigen HLA B27. MATERIALS AND METHODS: 118 ReA patients with associated intestinal and 82 ReA patients with associated urogenital infection were studied. The infection was identified bacteriologically, with agglutination reaction, enzyme immunoassay, direct and indirect immunofluorescence, culturing. HLA-antigens were studied in lymphocytotoxic test: locus A, B and C in all the patients, DR in 65 patients. RESULTS: ReA triggers were intracellularly parasite bacteria: facultative parasites in the enterocolitic variant (Yersinia, as a rule), obligate parasite in the urogenital (Chlamidia, as a rule). HLA B27 antigen was discovered in 77.5% of patients (RR 45.8), HLA DR1--in 48.4% of patients (RR 3.3). In urogenital variant HLA B27 antigen occurred more frequently than in enterocolitic: 87.8% (RR 95.6) versus 70.3% (RR 31.5); p < 0.01). In HLA-B27-positive patients compared to HLA-B27-negative ones there were higher ESR (p < 0.001), leukocyte count (p < 0.05), concentrations of CRP and alpha-2-globulins (p < 0.001). CONCLUSION: In HLA-B27-subjects optimal conditions exist for generalization of obligate parasites and favorable for production of facultative ones. The degree of association of ReA with HLA B27 antigens is dependent on adaptive features of microorganisms appearing in the process of evolution--obligaty and facultativeness of their internal parasitivity.

[Immunological and hematological reconstruction of recipients in bone marrow transplantation from closely related donors]. / Immunologicheskaia i gematologicheskaia rekonstruktsiia retsipienta pri transplantatsii kostnogo mozga ot blizkorodstvennogo donora.

Erythrocyte chimerism, graft versus host reaction, and course of disease were studied in patients subjected to bone marrow transplantation from 40 HLA identical sibs and 7 monozygotic twins. Disease relapses were observed in 35% of patients after allogenic and much more often in those after isogenic bone marrow transplantation. Relapses occurred in all patients subjected to transplantation from monozygotic twins. These results may be explained by the genetic and biological deficiencies of bone marrow cells from HLA identical sibs. 15% of recipients developed an acute graft versus host reaction after transplantation from HLA identical sibs; this is three times less than after transplantation from genetically unrelated donors, as reported elsewhere.

[Immunogenetic approaches to the study of leukemia in humans]. / Immunogeneticheskie podkhody k izucheniiu leikozov cheloveka.

One hundred and ten families having one child suffering from acute leukemia were included in HLA studies. These families were found to have unequal distribution of the parent HLA-haplotypes among the sibs. Three groups of families were conditionally distinguished. The first group showed the predominance of one parental, the second group of one maternal, and the third group of one maternal and one paternal HLA haplotypes. This suggests that impairment of the evolutionally derived principle of equal participation of both gamete types of each parent in the zygote formation is deleterious for the progeny.