Generic Imatinib in Chronic Myeloid Leukemia Treatment: Long-Term Follow-up.

BACKGROUND: Similar to the application of other generic drugs, the use of generic imatinib in the treatment of chronic myeloid leukemia (CML) leads to significant cost savings, but it also raises issues related to efficacy, safety, and quality. This study assessed the long-term outcome of CML patients after administration of generic imatinib. PATIENTS AND METHODS: The cohort of 83 patients was divided into 2 groups depending on whether generic imatinib was applied in the front-line setting or after switching from original imatinib. The groups were compared regarding rates of optimal treatment response, adverse events, and survival. RESULTS: In the first group, at the time of switching, rates of complete cytogenetic response experienced, and major molecular response were 95% and 87.5% of patients in the front-line generic imatinib group and the group that switched from original to generic imatinib, respectively. After 24 months of treatment with generic imatinib, the rates of sustained, lost, and experienced major molecular response were 72.5%, 15%, and 12.5%, respectively. In the group treated with front-line generic imatinib at 6 months, 67.4% experienced complete cytogenetic response, while for major molecular response at 12 and 24 months, it was 58.1% and 69.8%, respectively. Estimated 5-year overall survival in the group treated with front-line generic imatinib was 86.1%, while 10-year overall survival in the group treated with second-line generic imatinib was 93.8%. CONCLUSION: Results of this study with long-term follow-up are further evidence that generic imatinib is at least noninferior to original imatinib regarding efficacy and survival, both when provided initially and as a subsequent replacement for original imatinib.

Analyses of Treatment Outcome According to Age in Patients With Chronic Myeloid Leukemia Receiving Front-line Imatinib Therapy.

BACKGROUND: Previous studies have indicated that the effect of age at the diagnosis of chronic myeloid leukemia (CML) is minimized in patients treated with imatinib. The treatment response and survival rates were similar for younger and elderly patients. The aim of the present study was to evaluate the effect of age on the treatment outcomes in patients with CML receiving front-line imatinib therapy. PATIENTS AND METHODS: Using age, 101 patients were divided into 3 groups: young (age, 18-44 years; YP), middle-age (age, 45-64 years; MP), and elderly (age, ≥ 65 years; EP). The patients' clinical features, treatment responses, survival, and adverse events were evaluated. RESULTS: The complete cytogenetic response rates were similar in all 3 groups (81.8% in YP, 86.8% in MP, and 76.7% in EP; P = .328). However, the major molecular response rate was greatest in the MP group (84.2% vs. 63.6% in the YP and 60.0% in the EP group; P < .001). Most of the nonhematologic adverse events (all grades) were in the EP group (40.0% vs. 27.3% in the YP and 21.1% in the MP group; P = .005). The estimated 6-year event-free survival in the MP group (75.5%) was significantly greater than that in the YP group (58.6%) or EP group (43.4%). Also, the estimated 6-year overall survival rate in the EP group (73.5%) was significantly lower than that in the YP group (90.8%) and MP group (86.4%) (P < .001 for all). CONCLUSION: Our results have shown that middle-age patients have the best clinical outcomes, with the greatest rates of an optimal therapeutic response, longer event-free survival, and longer overall survival.

The significance of angiogenesis for predicting optimal therapeutic response in chronic myeloid leukaemia patients.

In this study the correlation and the prognostic value of the morphometric parameters of angiogenesis for optimal therapeutic response to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukaemia (CML), i.e. complete cytogenetic response (CCgR) and major molecular response (MMoR), were investigated. Microvascular density (MVD) and a number of different size- and shape-related morphometric parameters of microvessels of bone marrow biopsy from 40 CML patients and 20 controls were examined. Microvessels of bone marrow were examined by using immunohistochemical staining for CD34 and quantified in the region of the most intense vascularisation by using image analysis. CML patients had significantly higher angiogenesis parameters when compared with controls. A statistically significant correlation was found between some parameters of angiogenesis and evaluated CCgR and MMoR. For achievement of CCgR, lower values of MVD, minor axis, area, circularity, and roundness and higher value of aspect ratio, while for achievement of MMoR only lower values of MVD have been identified as positive prognostic factors. Besides confirming increased angiogenesis in CML patients, this study also demonstrated prognostic significance of the degree of angiogenesis for the clinical outcome and identified angiogenic predictive factors for achieving optimal response on TKIs therapy.

The importance of Myd88 L265P mutation, clinical and immunohistochemical prognostic factors for the survival of patients with diffuse large B-cell non-Hodgkin lymphoma treated by immunochemotherapy in southeast Serbia.

PURPOSE: Immunochemotherapy used in the treatment of non-Hodgkin diffuse large B-cell lymphoma (DLBCL) modifies the course of disease and has a positive effect on overall survival (OS). The purpose of this study was to verify the existence of the important Myd 88 mutation and other immunohistochemical factors on disease prognosis in patients with DLBCL in southeast Serbia. METHODS: Immunohistochemical expression of CD10, Bcl- 2, Bcl-6, Ki-67 and MUM 1 was performed using paraffin blocks of DLBCL. Molecular-genetic study of MyD88 L265P gene polymorphism was done by isolation of genomic DNA from paraffin embedded tissue by means of polymerase chain reaction (PCR). RESULTS: Immunochemotherapy (rituximab+CHOP/R-CHOP) significantly improved the overall survival (OS) of patients with DLBCL compared with patients treated with CHOP alone (p<0.0001). OS in the R-CHOP group was longest in patients with International Prognostic Index (IPI) 2 score (p=0.012) and IPI 4 score (p=0.024). Patients with Bcl-2 +, and MUM 1+ benefited from R-CHOP and their expression had no effect on OS. Analysis of restriction fragment length on the genomic DNA showed a homozygous normal TT genotype. CONCLUSION: Addition of rituximab to CHOP standard protocol improved the OS rate in patients with DLBCL and altered the character and significance of previously recognized prognostic factors. IPI score in the immunochemotherapy era could not reveal possible predictive factors of poor prognosis which would help identify a high-risk subgroup of newly diagnosed DLBCL. In the patient population from Southeast Serbia pathological signaling pathway achieved by Myd 88 L265 mutation was not responsible for the development of DLBCL.

Serbian lymphoma study group: demografic characteristics of 257 patients with follicular lymphoma.

BACKGROUND/AIM: Follicular lymphoma (FL) is a B-cell tumor usually with indolent clinical course, yet in some cases the course of the disease can be very aggressive. The aim of the research was to determine distribution of patients into prognostic groups based on the International Prognostic Index (IPI) and Folicular Lymphoma International Prognostic Index (FLIPI) criteria, as well as to determine the importance of classifying patients into the prognostic groups, since this could potentially have the influence on selection of the treatment modality. METHODS: The retrospective study was performed on 257 patients with follicular lymphoma diagnosed between January 2000 and April 2011. RESULTS: Based on the IPI score, 153 (59.53%) patients had low risk, 57 (22.18%) low intermediate risk, 15 (5.84%) high intermediate risk, 9 (3.50%) high risk, whereas the classification of 23 patients diagnosed with FL remained with unknown risk according to the IPI. Based on the FLIPI prognostic index, 113 (43.97/6) patients had low risk, 70 (27.24%) intermediate risk and 51 (19.84%) high risk, whereas the classification of 23 (8.95%) patients remained unknown. On the basis of the FLIPI 2 prognostic index, 48 (18.68%) patients had low risk, 145 (56.42%) intermediate risk and 41 (15.95%) high risk. The classification into prognostic groups for 23 (8.95%) patients remained unknown. According to the IPI, FLIPI and FLIPI 2 there were the patients that required treatment in all the risk groups. CONCLUSION: The FLIPI and FLIPI 2 effectively identify patients at high risk, thus helping in treatment decision for each single patient.

Improved prediction of clinical outcome in chronic myeloid leukemia.

We sought to develop and compare prognostic models, based on clinical and/or morphometric diagnostic data, to enable better prediction of complete cytogenetic response (CCgR). This prospective longitudinal study included a consecutive series of patients with chronic myeloid leukemia (CML) who were started on imatinib therapy. Logistic regression analysis using backward selection was performed with CCgR at 6, 12, and 18 months as the outcome variables. We evaluated both calibration and discrimination of the model. Internal validation of the model was performed with bootstrapping techniques. A total of 40 patients on imatinib therapy were included in the final analysis. Of these, 25 (62.5 %), 29 (72.5 %), and 32 (80 %), respectively, achieved CCgR at 6, 12, and 18 months after initiation of imatinib. Models included EUTOS score on diagnosis and one of the following morphometric parameters: microvascular density, length of the minor axis, area or circularity of the blood vessel. Models including morphometric parameters and EUTOS score were superior for prediction of CCgR at 6, 12, and 18 months. In particular, the superior models showed better specificity than EUTOS score alone. Using morphometric parameters in conjunction with EUTOS score improves prediction of CCgR. If validated, these models could aid in individual patient risk stratification.

[Evaluation of coagulation factors in fresh frozen plasma treated with riboflavin and ultraviolet light].

BACKGROUND/AIM: Pathogen inactivation in blood products using riboflavin and ultraviolet (UV) light represents a proactive approach to blood safety, not only for known infectious agents but also for new ones or not yet recognized as threats to the blood supply. This method inactivates a virus, bacteria, fungus, or protozoan pathogen from the blood product without damaging its function or shelf-life. The aim of the study was to study the influence of photoinactivation using riboflavin on the concentration of coagulation factors and coagulation inhibitors in plasma that was treated before freezing. METHODS: The examination included 30 units of plasma, separated from whole blood donated by voluntary blood donors around 6 h from the moment of collection. They were treated by riboflavin (35 mL) and UV rays (6.24 J/mL, 265-370 nm) on Mirasol aparature (Caridian BCT Biotechnologies, USA) in approximate duration of 6 min. The samples for examining were taken before (K - control units) and after illumination (I - illuminated units). RESULTS: Comparing the middle values of coagulation factors in the control and illuminated units we noticed their statistically significant decrease in illuminated units (p < 0.001), but the activity of coagulation ones was still in the reference range. The most sensitive coagulation factors to photoinactivation were FVIII, FIX and FXI (21.99%, 20.54% and 17.26% loss, respectively). Anticoagulant factors were better preseved than coagulation factors. CONCLUSION: Plasma separated from whole blood donation within 6 h, treated with riboflavin and UV light within 6 h from separation and frozen at temperature below -30 degrees C within 24 h, shows good retention of pro- and anticoagulation activity.

[Factors associated with achievement and durability of cytogenetic response in patients with chronic myeloid leukemia treated with imatinib].

BACKGROUND/AIM: Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia and become the standard of care for this disease. The aim of this study was evaluation and analysis of cytogenetic response in different intervals and risk groups as well as finding association between pre-treatment characteristics and later probability of achievement of major cytogenetic response. METHODS: We analyzed a total of 22 adult patients with newly diagnosed Philadelphia positive early chronic phase chronic myeloid leukemia treated at our institution from June 2006 to December 2009. RESULTS: The median follow-up time for patients during treatment with imatinib was 25.7 months (range, 12-42 months). A complete hematologic response was achieved in all of the analyzed patients within 6 months from the start of the treatment. The major cytogenetic response rate was 81.8%, and the complete cytogenetic response rate was 72.7%. The patients with low or moderate relative risk had the rate of complementary achieving major and complete cytogenetic response of 75-90%. A multivariate analysis identified the following independent prognostic factors for achieving major cytogenetic response: the absence of splenomegaly, white blood cell count less than 10 x 10(9)/L, the platelet count less than 450 x 10(9)/L, the presence of less than 5% of bone marrow blasts and basophils, the absence of blasts in peripheral blood, the presence of less than 7% of basophils in peripheral blood. CONCLUSION: Patients who early achieve complete and major cytogenetic response as well as those with low and moderate relative risk have a higher rate of achieving and maintaining complete cytogenetic response. There are also characteristics of patients before treatment that may indicate the treatment outcome.

Hematopathologic and cytogenetic findings in imatinib mesylate treated chronic myelogenous leukemia patients: 2.5 years' experience.

BACKGROUND/AIM: Imatinib mesylate, a tyrosine kinase inhibitor with specific activity against the breakpoint cluster region--Abelson murine leukemia (BCR-ABL) tyrosine kinase has been developed for treatment of chronic myelogenous leukemia (CML). Its hematologic and cytogenetic effects have been evaluated in a series of clinical trials. The aim of this study was to report hematologic and cytogenetic response in CML patients during the treatment with imatinib mesylate. METHODS: A total of 21 patients were treated and observed from July 2006 to December 2008. The median time from CML diagnosis was no more than 12 months, so all the patients received previous treatment with hydroxyurea for which the median time was 3 months. The patients received imatinib mesylate in an effective oral dose of 400 to 800 mg daily, which was followed with peripheral blood counts, bone marrow examination, and cytogenetic studies at 6, 12, 18 and 24 months. RESULTS: Complete hematologic responses were reported for 19 (90.48%) of 21 patients studied. Among 19 patients who had a response, 16 (86%) did so within 3 months. The best cytogenetic response rate at any time during the study treatment with imatinib mesylate, among 14 patients in which cytogenetic response evaluated was: complete cytogenetic response in 7 (50%) patients, partial cytogenetic response in 6 (42.9%) patients and minor cytogenetic response in 1 (7.1%) patient. No patients had progressed to accelerated or blastic phase. The most frequent adverse effects that seemed to be related to treatment with imatinib mesylate were edema and musculoskeletal pain; overall, most were mild. Only one patient discontinued treatment because of hematologic toxic effects. CONCLUSION: The results obtained in this study confirm that imatinib mesylate induces a complete hematological and cytogenetic response in a high percentage of patients with chronic-phase CML.

Prognostic factors associated with complete cytogenetic response in patients with chronic myelogenous leukemia on imatinib mesylate therapy.

INTRODUCTION: Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has proved to be most effective therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. Imatinib induces complete haematological and cytogenetic response in high percentage of patients. OBJECTIVE: The aim of this study was to identify potential prognostic factors before beginning treatment with imatinib associated with complete cytogenetic response. METHODS: We analyzed 20 patients with newly diagnosed Philadelphia positive chronic myelogenous leukemia treated at our institution from June 2006 until May 2009. These patients were treated with imatinib mesylate in oral dose of 400 to 800 mg daily. Complete blood counts were performed every month, while serum chemistry evaluations and bone marrow evaluations including morphology and cytogenetics were performed every 6 months. RESULTS: Of the 20 patients analyzed in this study, 19 (95%) achieved complete haematologic response within three months. In all patients cytogenetic analyses were done and all have achieved absolute cytogenetic response. The best cytogenetic response rate at any time during study treatment among 20 patients was: complete cytogenetic response in 15, partial cytogenetic response in three and minor cytogenetic response in two patients. Among 11 observed base-line patients' characteristics five were independent predictors of a high rate of complete cytogenetic response; the absence of blasts and basophils in peripheral blood, the presence of less than 5 percent of bone marrow blasts, white blood cell count less than 10 x 10(9)/L and the absence of splenomegaly (p < 0.01). CONCLUSION: Our results showed that some pre-treatment characteristics of patients might be the cause of differences in treatment outcome. On the basis of this analysis, we identified several pre-treatment patients' characteristics to be independent prognostic factors for achievement of complete cytogenetic response.

Polymorphisms of tumor-necrosis factor-alpha - 308 and lymphotoxin-alpha + 250: possible modulation of susceptibility to apoptosis in chronic lymphocytic leukemia and non-Hodgkin lymphoma mononuclear cells.

Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) have been shown to play an important role in the pathogenesis of limphoproliferative disease. Both cytokines regulate cell-survival and cell-death in leukemic cells. TNF-alpha and LT-alpha are highly produced in chronic lymphotic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients. Genetic polymorphism within regulatory regions of these cytokine genes can alter their expression levels. This study investigates an influence of TNF-alpha - 308 and LT-alpha + 250 polymorphisms on the activity of alkaline DNase in mononuclear cells of both patient groups as a potent biochemical marker of DNA fragmentation in the terminal phase of apoptosis. Study was performed on mononuclear cells of CLL and NHL patients. SNP were obtained by PCR-RFLP method. The activity of alkaline DNase was measured by spectrophotometric method. The study provided evidence of the influence of TNFG/A genotype and A alleles in the susceptibility to NHL, since the association of LT-alphaG/G genotype with CLL was observed. High-producing TNF-alpha - 308/LT-alpha + 250 heterozygous haplotype is associated with high NHL incidence. The investigated SNP influence the activity of alkaline DNase in CLL and NHL patients. The observed polymorphisms may modulate susceptibility of leukemic cells to apoptosis by way of DNase activity.

[External fixation in the treatment of open tibial shaft fractures].

BACKGROUND/AIM: Besides the conquasant fractures, open tibia shaft fractures belong to the group of the most severe fractures of tibia. Open tibia shaft fracture is one of the most common open fractures of long bones. They most frequently occur as a result of traffic accidents caused by the influence of a strong direct force. METHODS: Within the period from January, 2000 to December 31, 2005 at the Clinic for Orthopaedics and Traumatology, Clinical Center Nis, 107 patients with open tibial fractures were treated. We analyzed 96 patients with open tibial fracture. In the series analyzed, the male sex was prevalent--there were 74 men (77.08%). The mean age was 47.3 years. The youngest patient was 17 years old, while the oldest patient was 79. According to the classification of the Gustilo et al. in the analysed group there were 30 (31.25%) open tibial fractures of the I degree, 31 (32.29%) of the II degree, 25 (26.05%) of the III A degree, 8 (8.33%) of the III B degree and 2 (2.08%) of the III C degree. In 95 of the patients the treatment of open tibia shaft fractures consisted of the surgical treatment of wound and the external fixation of the fractured bone using "Mitkovic" type external fixator with a convergent method of pin applications. One primary amputations had been done in patients with grade IIIC open tibial fracture with large soft tissue defect. RESULTS: Of the 96 open tibial fractures available for follow-up, 73 (76.04%) healed without severe complications (osteitis, pseudoarthrosis, valgus malunion and amputation). There were nine (9.38%) soft tissue pin track infections and six (6.25%) superficial wound infections. The mean time of union was 21 (14-36) week. Among severe local complications associated with open tibial fractures, in eight patients (8.33%) was registered osteitis, and in nine patients (9.38%) fracture nonunion and the development of pseudoarthrosis. Three of the patients (3.13%) had more than 10 degree valgus malunion. In one patients (1.04%) deep pin track infection developed. Two patients (2.08%) had below the knee amputation (one primary in patient with type III C open fracture and one secondary after the development of deep infections). CONCLUSION: Surgical treatment of wounds, external fixation, leaving the wounds open and performing necessary debridements, adequate drug therapy administration are essential for obtaining good results in patients with open tibial shaft fractures.

[Morphometrical analysis of bone marrow metamyelocyte in pernicious anemia].

INTRODUCTION: In pernicious anemia besides the presence of megaloblasts in the bone marrow, changes in myeloid series were seen; being the most evident among the metamyelocyte. The aim of this study was to perform the quantification of metamyelocyte of the bone marrow in pernicious anemia. MATERIAL AND METHODS: Between 2000-2006 in the Clinic of Hematology-Nis, 68 patients with pernicious anemia were examined and 30 with dyspeptic syndrome (control group). The group of patients with pernicious anemia in relation to pathohistologic changes of gastric mucosa was divided into three sub-groups. Morphometrical analysis of metamyelocyte of the bone marrow was carried out by the application of the double netlike system (B100). The following parameters were used: relative surface, contour length, absolute surface of nucleus and cytoplasm, absolute contour nucleus and cytoplasm density, shaped nucleus and cytoplasmic factor and nuclear-cytoplasmatic ratio of metamyelocytes. RESULTS: Relative surface, contour length, absolute surface and contour density of nucleus and cytoplasm of metamyelocytes increased simultaneously with the degree of atrophic gastritis. Shaped nucleus and cytoplasmic factor and nuclear-cytoplasmatic ratio of metamyelocytes decreased in all examined groups in relation to the control group. CONCLUSION: Not only are bone marrow erythroid elements scoped with megaloblastic changes but the changes on the level of leukocyte cells as well. The result of this is the phenomena of giant metamyelocytes.

[Treatment of trochanteric femoral fractures with double dynamic internal fixation].

INTRODUCTION: Trochanteric fractures are extracapsular fractures of the proximal femur. The increasing number of trochanteric fractures is a great sociomedical problem. These fractures usually occur in elderly people (older than 65 years) with osteoporosis. Lateral and frontal falls are the most frequent cause of trochanteric fractures in the elderly. The aim of this paper is to present our results of applying the Mitkovic selfdynamisable internal fixator (SIF). MATERIAL AND METHODS: From January 2001 to December 2005, 238 patients with trochanteric femoral fractures were treated operatively using the Mitkovic selfdynamisable internal fixator at the Clinic of Orthopeadics and Traumatology in Nis. The average patient age was 69, 11 years (range 17 to 88). In the analyzed group there were 152 (64%) female and 86 (36%) male patients, whereas patients in the eighth 101 (43%) and seventh 65 (27%) decade of life prevailed. RESULTS: Excellent results in the treatment of trochanteric femoral fractures with a Mitkovic dynamic internal fixator were achieved in 143 (60%) patients, good in 49 (21%) patients, poor in 41 (17%) and unsatisfactory in 5 (2%) patients. DISCUSSION AND CONCLUSION: The treatment of trochanteric fractures may be operative and nonoperative. The aim of the operative treatment, considered to be the "gold standard" for these fractures, is to restore the patient's pretraumatic activity level and to reduce life-threatening complications. The operative stabilization is performed using various types of implants. Surgical treatment by using dynamic implants is a method of choice in the treatment of trochanteric fractures. Internal fixation using the Mitkovic selfdynamisable internal fixator is a method of choice in the treatment of trochanteric femoral fractures, providing dynamization and compression of the fracture site in two axes (axis of the femoral neck and femoral diaphyseal axis) and balanced biomechanical 3D.

[Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia].

BACKGROUND/AIM: Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA), as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like (ECL) carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. METHODS: During the period from 2000-2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE); histochemical AB-PAS (pH 2.5), cytochemical argyrophilic Servier-Munger's and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA) method. The obtained results were statisticaly calculated by using Student's t test. RESULTS: Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05) as well as an average number of ECL cells. CONCLUSION: We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia.

[Implications of HLA linkage disequilibrium phenomenon in finding unrelated volunteer bone marrow donors].

INTRODUCTION: The distribution of HLA genes and haplotypes in the normal population is of considerable importance in disease susceptability studies, population and genetic studies and tissue and organ transplantation. The HLA phenotype frequencies can be used for the estimation of the probability of finding phenotypically identical unrelated volunteer bone marrow donors. It has been presumed that patients with HLA haplotypes in strong linkage disequilibrium, a have higher probability of finding HLA identical unrelated donors than others. MATERIAL AND METHODS: HLA gene and haplotype frequencies were calculated, as well as delta values and their significance. The implications of HLA disequilibrium phenomenon in unrelated donor search, was investigated by calculating the correlation coefficient between frequencies of haplotypes showing significant delta values and the linkage disequilibrium coefficient, as well as between the average number of donors necessary for research. RESULTS: Haplotypes showing the highest delta values are at the same time the most frequent haplotypes (A1B8:0,1188 and 0,145; A3B35:0,0722 and 0,1;A2B12:0,055 and 0,105). In patients who have both haplotypes showing significant delta values (e.g. A2B5/A3B35), the number of donors necessary for research is clearly lower than in patients who have only one given haplotype, or have no such haplotypes. CONCLUSION: Our results showed that patients with HLA haplotypes showing significant delta values have a higher probability of finding HLA identical unrelated donors.

[External fixation combined with limited internal fixation in the treatment of pilon tibia fractures].

BACKGROUND/AIM: Intraarticular fractures of the tibial plafond (pilon fractures) belong to the group of most severe fractures. They are usually caused by high-energy trauma and frequently associated with a marked soft-tissue damage. Surgical treatment has replaced the traditional nonoperative treatment. The aim of this study was to present the results of the treatment of distal tibial intraarticular fracture by the use of internal fixation, as well as the combination of minimal internal fixation and external fixation. METHODS: The study included 47 patients with pilon tibia fractures who went through at the Clinic for Orthopedics and Traumatology, School of Medicine, Nis (1995-2004). Within the analayzed group there were 33 (70.2%) males and 14 (29.8%) females. The patients mean age was 45.8 years. In the first group, which consisted of 22 patients, open reduction and internal fixation of both the tibia and the fibula was performed in the two separate incisions. The second group consisted of 25 patients managed with external fixation by external fixator "Mitkovic" with limited internal fixation. Besides external fixation, a minimal internal fixation was performed by the use of Kirschner wires and screws. The patients were followed-up inside a 24-months-period. Results. The obtained was a substantially high number of complications after open reduction and internal fixation in the group of patients. There was no difference in a long-term clinical outcome. Postoperative osteitis, as the most severe complication in the management of closed pilon tibia fractures, was not registered in the second group. CONCLUSION: Considering the results obtained in this study, it can be concluded that external fixation by the "Mitkovic" external fixator with the minimal internal fixation is a satisfactory method for the tratment of fractures of the tibial plafond causing less complications than internal fixation.

[Successful treatment of acquired haemophila associated with psoriasis--case report].

Acquired factor VIII (FVIII) inhibitor causes a rare but life-threatening form of bleeding disorder, owing to the formation of autoantibodies against FVIII. Treatment modalities include the use of immunosuppressive drugs, such as cyclophosphamide and corticosteroids, plasmapheresis, and i.v. immunoglobulin. The case of a 67-year-old patient with acquired FVIII inhibitor and psoriasis presented us with a serious bleeding complication. Bleeding reacted poorly to therapy with corticosteroids and cyclophosphamide. Treatment with cyclosporin, however, resulted in a prompt and complete response. The lack of side effects and the relatively quick response suggest that cyclosporin A should be tried as a frontline treatment for patients with acquired FVIII inhibitor.