[Role of antithymocyte globulin in reducing the incidence of complications after allogeneic hemopoietic cell transplantation].

AIM: To evaluate the efficacy of antithymocyte globulin (ATG) used in conditioning modes before allogeneic hemopoietic cell transplantation (allo-HCT) and its effect in reducing the incidence of posttransplantation complications. SUBJECTS AND METHODS: The study assessed the results of 92 allo-HCTs depending on the presence or absence of ATG in conditioning modes, the doses of Atgam (60 mg/kg or more), the presence or absence of acute leukemia (AL) in remission before HCT. RESULTS: In patients with AL in remission receiving ATG in conditioning modes (Atgam 60 mg/kg or thymoglobulin 7.5 mg/kg), overall three-year survival was 60%. Increasing the dose of Atgam up to more than 60 mg/kg resulted in higher transplantation-associated mortality (TAM) rates than did with the Atgam dose of 60 mg/kg (p < 0.01). CONCLUSION: Allo-HCT is the treatment of choice for patients with AL in the presence of an HLA-identical related or unrelated donor. The use of Atgam in a course dose of not more than 60 mg/kg or thymoglobulin 7.5 mg/kg in conditioning modes is associated with low TAM rates and higher overall survival in earlier-stage disease in complete clinical hematological remission as compared with those in patients with expanded-stage AL, rather than in AL in remission at the start of conditioning before HCT.

[The use of allogeneic bone marrow transplantation and immunosuppressive therapy in the treatment of patients with acquired aplastic anemia].

AIM: To evaluate the efficiency of related and unrelated allogeneic bone marrow transplantation (alloBMT) 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.

[Use of various nutritional support regimens in patients with transplanted hematopoietic stem cells].

AIM: To study the impact of modified nutritional support (NS) versus standard NS on therapy tolerability and posttransplantation in patients with oncohematological diseases. SUBJECTS AND METHODS: Fifty-three patients, who had been diagnosed as acute myeloblastic (n = 19) or acute lymphoblastic (n = 16) leukemias, lymphomas (n = 10), and other oncohematological diseases (n = 8) and had received large-dose polychemotherapy followed by hematopoietic stem cell transplantation (HSCT), were prospectively examined. The control group (n = 27) used standard NS (NS was prescribed when gastrointestinal (GI) events occurred; on day 1 after HSCT, the study group (n = 26) had modified NS added by glutamine dipeptide (0.57 g/kg/day). Energy demands were 35 kcal/kg/day; protein requirements were 1.5-1.7 g/kg/day. Artificial nutrition preparations were daily given through infusion pumps for 24 hours. In both groups, the criteria for NS discontinuation were natural assimilation of 60% of the required energy within 3 consecutive days or day 14 after HSCT when Gl function was preserved. RESULTS: The patients receiving modified NS showed reductions in the incidence and severity of mucositis (p = 0.05), a less significant decrease in the laboratory and anthropometric indicators of nutritional status (p = 0.01), and a better hospital outcome on day 100 after HSCT (p = 0.01). There were no differences in the rate and severity of acute graft-versus-host reaction (p = 0.7%) and in one-year overall survival (p = 0.7%). CONCLUSION: As compared with standard NS, modified NS enables a patient to sustain negative consequences of the conditioning regimen, HSCT in the early posttransplantation period.

[The experience in non-relative allogenic transplantation of stem hemopoietic cells in the Clinic of Bone Marrow Transplantation at I.P. Pavlov St-Petersburg Medical Academy].

AIM: To evaluate efficacy of allogenic transplantation of hemopoietic stem cells (allo-THSC) from non-relative donor in patients with hematological diseases in the Clinic of Bone Marrow Transplantation at L.P. Pavlov St-Petersburg Medical Academy for the period 2000-2006. MATERIAL AND METHODS: A total of 84 allo-THSC from non-relative donor to patients aged from 10 months to 65 years (median 18 months, 44 years) was carried out. RESULTS: Six-year overall survival (OS) in all the patients was 51.4%, in remission of AML--66.7%, ALL--33%, depending on the presence or absence of acute reaction graft versus host reaction (GVHR)--54 and 50.9%, chronic FVHR--75.6 and 58.2%, blood group compatibility or incompatibility in donor/recipient pairs--58.4 and 47.9%, by gender--61.4 and 40.6%, in use of HSC of the bone marrow--58.3%, peripheral blood--26.7%. OS in the dose of transplanted CD 34+ cells per 1 kg body mass < 5.0 x 10(6)/kg--173%, in the dose 5.0--8.0 x 10(6)/kg--38.8%, > 8.0 x 10(6)/kg--35.5%. Acute GVHR developed in 56% patients, chronic--in 20%, hemorrhagic cystitis--in 27.7%, bacterial, cytomegalovirus and fungal infection--in 10, 70 and 30%, respectively. The causes of death were acute GVHR (20%), infection 99%), polyorganic failure (4%), transplant rejection (5.3%), recurrence (18.7%). CONCLUSION: Bone marrow transplantation clinics in the Russian Federation must develop all kinds of allo-THSC--relative, non-relative and haploidentical using bone marrow, peripheral blood, umbilical blood as the source of HSC. It is necessary to create a national register of non-relative donors.

[Incidence and characteristics of complications in aplastic anemia patients treated with antilymphocytic globulin]. / Chastota i kharakter oslozhnenii terapii antilimfotsitarnym globulinom u bol'nykh s aplasticheskoi anemiei.

AIM: To examine frequency and characteristic features of complications arising in administration of domestic antilymphocytic globulin (ALG) in patients with aplastic anemia (AA). MATERIAL AND METHODS: From 1980 to 2000 125 patients with AA were treated with ALG made in Russia. Two and three courses of ALG were performed in 25 and 8 patients, respectively. RESULTS: The treatment was complicated most often with allergic reactions (AR) observed in 42.4% patients, hemorrhagic syndrome (HS) and infectious complications (IC). Goat ALG was more allergic than rabbit ALG (46.2 vs 34.6%, respectively). If the second course was made with ALG of the same kind, AR occurred in 37.5% patients while ALG of the different kind produced complications only in 11.8% patients. HS was recorded in 37.3% patients, its frequency was unrelated to ALG kind and was not severe (71.2%). IC occurred in 16.5% patients, their occurrence was also unrelated to the ALG kind and were of the first degree in 63.6%. CONCLUSION: Domestic ALG often results in AR. To reduce frequency and severity of complications in ALG treatment, it is recommended to use long intravenous infusions (12-18 h) and change ALG kind in subsequent ALG courses.

[Levels of complement components in plasma of onco-hematologic patients with defective hemopoiesis]. / Soderzhanie komponentov komplementa v plazme onkogematologicheskikh bol'nykh pri nedostatochnosti gemopoéza.

Immunochemical assay using monoclonal antibodies was carried out to determine levels of a number of complement components (C3 and its derivatives-C4 and C5) and immunoglobulins (lg) in plasma of patients with onco-hematological diseases involving defective hemopoiesis: leukemia, myelodysplastic syndrome (clonal diseases) or aplastic anemia (delayed clonal disease). The most significant disorders were registered in the concentrations of component C3 and its derivatives. In acute leukemia, the nature and extent of C3 splitting was found to depend on disease while Ig level-on stage. Myelodisplasia usually involved a 2-3-fold decrease in C3 level matched by a rise in the concentrations of its derivatives-C3-like form and C3a fragment. Reduced C3 levels matched by increased ones of Ig were observed in some cases of aplastic anemia. It is suggested that disturbances in complement component level may cause changes in cascade reactions of the complement in onco-hematological patients and thus indirectly influence immune response regulation processes.

[Bone marrow transplantation in the treatment of acute leukemias]. / Transplantatsiia kostnogo mozga v lechenii ostrykh leikozov.

The effect of bone marrow transplantation on 4-year leukemia recurrence-free survival of patients with acute myeloid and lymphoblastic leukemia has been studied in 11 and 16 patients, respectively. Autologous and allogeneic bone marrow transplantations during the first complete remission of acute leukemia have improved the survival compared to chemotherapy from 44 to 75% in acute myeloid leukemia and from 35 to 60% in acute lymphoblastic leukemia.

[Clinical experience using the cryoprotector "hecmolit" in performing autologous bone marrow transplantation]. / Opyt klinicheskogo primeneniia krioprotektora "gekmolit" pri provedenii autologichnoi transplantatsii kostnogo mozga.

The authors summarize clinical evidence obtained on the efficacy of a new Russian cryoprotector hecmolit in the conduction of autotransplantation of 8 patients with acute leukemia. The markers of the preserved hemopoietic potential of the unfrozen bone marrow were the amount of myelokaryocytes, their viability in the test with vital stain, CFU-GM level. Infusions of the marrow suspension incorporating hecmolit (120-180 ml) produced minimaL side effects. After thawing myelokaryocytes remained in the amount 81.7 +/- 8.2% or 1.6 +/- 0.4 x 10(8) cell / kg, on the average. Estimation of the aggregates in terms of the weight revealed that hemopoietic potential was sufficient for the transplant survival (2.9 +/- 0.7 x 10(3) CFU-GM/kg) though only 50 +/- 10% of CFU-GM remained safe. Hecmolit tolerance was satisfactory. The preparation is thought convenient for bone marrow transplantation practice.

[The treatment results in patients with aplastic anemia using different doses of antilymphocyte globulin]. / Rezul'taty lecheniia bol'nykh aplasticheskoi anemiei razlichnymi dozami antilimfotsitarnogo globulina.

The authors present 5-year survival of 64 patients with aplastic anemia (AA) divided into 2 groups. Group 1 received antilymphocytic globulin (ALG) in low doses (1-5 mg/kg), group 2 in high doses (10-30 mg/kg). Survival of patients with severe AA in group 1 made up 28.5%, with mild AA 90.1%. Overall survival in group 1 was 64.4%, in group 2 53.8%. Overall toxicity came to 48.6%. By resultant complications high and low ALG doses did not differ. The authors propose to use low doses of ALG in mild disease whereas in severe condition high ALG doses are thought adequate.

[The rheologic aspects of washed donor erythrocytes]. / Reologicheskie aspekty otmytykh donorskikh éritrotsitov.

Washing off donors' red blood cell pack with NaCl isotonic solution results in improvement of red blood cell rheologic properties: their aggregation reduces, deformability increases, osmotic resistance rises. Heparin addition to the washing off solution in a dose of 5 IU/ml prevents development of antiheparin activity in red blood cells after washing off. Application of washed-off red blood cells of donors has advantages as compared to transfusion of the whole blood.

[Hemosorption combined with intensive measures in hemoblastoses]. / Gemosorbtsiia v komplekse intensivnykh meropriiatii pri gemoblastozakh.

The results of 24 applications of hemosorption procedure in 19 cases of acute leukemia, chronic myeloleukemia, chronic lymphocytic leukemia and multiple myeloma are discussed. Hemosorption in conjunction with infusions of albumin, hemodesum, rheopolyglucinum, saline and glucose solutions may be recommended for severe and extremely severe toxemia. A high efficiency of the procedure application at different stages of leukemia development in cases of toxemia syndrome, toxico-allergic hepatitis and sepsis was observed.

[Characteristics of the correction of the blood aggregate condition during extracorporeal hemosorption in hematologic patients]. / Osobennosti korrektsii agregatnogo sostoianiia krovi pri ekstrakorporal'noi gemosorbtsii u gematologicheskikh bol'nykh.

The authors described experience in the use of the method of extracorporal hemosorption in patients with grave hemoblastoses. Nineteen of them were given 24 hemosorptions. Though severe disorders of the blood aggregate condition, thrombocytopenia (65%) and signs of disorder of thrombocyte function were present, no hemorrhagic complications during hemosorption were observed. Mean doses of heparin taking account of its consumption for sorbent treatment were 200 I.U./kg of body mass in thrombocytopenia and 300 I.U./kg of body mass with the normal level of thrombocytes. The refusal of protamine-sulfate administration to neutralize residual heparin at the end of operation for fear of possible complications made it possible to restore the initial indices of homeostasis 20 hrs. after sorption. This scheme for examination of the homeostasis system made it possible to control the adequacy of patient's heparinization and to avoid complications of the blood coagulation system.