Analysis of Factors that Influence Hematopoietic Recovery in Autologous Transplanted Patients with Hematopoietic Stem Cells from Peripheral Blood.

BACKGROUND: Successful hematopoietic stem cell transplantation (HSCT) requires a rapid and durable hematopoietic recovery. AIM: The aim of our study was to analyse factors that influence hematopoietic recovery after autologous HSCT. MATERIALS AND METHODS: Multiple regression analysis was used to analyse factors affecting neutrophil and platelet engraftment in 90 autologous transplanted patients - 30 with acute myeloid leukaemia (AML), 30 with lymphoma and 30 with multiple myeloma (MM) from 2008 till 2016. RESULTS: The neutrophil recovery in AML patients was significantly influenced by transfusion support with random-donor platelets, sex and number of transplanted mononuclear cells (MNC) and CD34+ cells; and in lymphoma patients, it was influenced by sex, age, mobilisation strategy and some transplanted MNC. The influence of investigated factors on neutrophil engraftment in MM patients was not statistically significant. The platelet recovery in AML patients was influenced by transfusion support with random-donor platelets; in lymphoma patients, it was influenced by sex, age, time from diagnosis to harvesting and time from diagnosis to HSCT; and in MM patients it was influenced by transfusion support with random-donor platelets. CONCLUSION: Additional studies are necessary to better understanding of engraftment kinetic to improve the safety of HSCT and to minimise potential complications and expenses related to HSCT.

Early and Late Complications in Patients with Allogeneic Transplantation of Hematopoietic Stem Cell - Case Report.

BACKGROUND: Allogeneic hematopoietic stem cells transplantation (HSCT) is a curative intervention in patients with haematological malignant and non-malignant diseases, immunodeficiency, autoimmune, and other genetic diseases. Early complications are complications that are occurring in the first 100 days, while complications arising after the 100th day of transplantation belong to late complications. CASE REPORT: Forty-nine years old patient with AML treated with allogeneic HSCT from HLA-identical (sister) donor. Ascertained and display of early (acute Graft versus host disease (GvHD) and late complications (chronic GVHD, infections, cataract, secondary malignancy with MS deposits) are made, that emerged after the patient transplantation. CONCLUSION: Rapidly growing population of patients that undergo allogeneic HSCT creates an obligation to educate patients and physicians about observed late complications that occur after this therapy.

Diversities of Calreticulin Gene Mutations in Macedonian Patients With Essential Thrombocythemia.

BACKGROUND: Acquired calreticulin (CALR) gene mutations are one of the molecular hallmarks of essential thrombocythemia (ET). It has been suggested that patients with ET with CALR mutations are associated with a distinct clinical phenotype. PATIENTS AND METHODS: We evaluated the clinical and molecular features of 150 patients with ET followed over a period of 15 years. The screening for the presence of insertion/deletion mutations in CALR exon 9 was done with a fluorescent polymerase chain reaction/capillary electrophoresis procedure. Sanger sequencing of CALR exon 9 was used for the characterization of mutations and for the analysis of triple-negative patients. RESULTS: CALR mutations were detected in 42 (28%) patients. The most common CALR mutations were type 1 and type 2, which were present in 11 (26.2%) and 20 (47.6%) patients, respectively. Additionally, 10 different small insertion/deletions (3 known and 7 new) were detected in 11 patients, resulting in an altered calreticulin C-terminal end. The clinical characteristics of all CALR+ patients with ET were in line with previously published data for this subset of patients. CONCLUSION: Our results showed that a wide range of different CALR mutations are associated with a distinct ET clinical phenotype that is associated with the male gender, younger age at diagnosis, higher platelet and lower leukocyte and erythrocyte counts and lower hemoglobin level, and a milder clinical course. The relatively high frequency of new insertion/deletion mutations indicate that the use of fluorescent polymerase chain reaction followed by capillary electrophoresis is the method of choice for the analysis of these defects.

Acute graft versus host disease in hematopoietic stem cell alotransplant recipients.

INTRODUCTION: The transplantation of hematopoietic stem cells (HSCT) is a therapeutic intervention where the hematopoietic stem cells and the cells originating from them are being removed and replaced by the normal stem cells of donor or the patient him/her-self. HSCT today represent standardized biological manipulation for treating malignant, genetic and autoimmune diseases. The application of allogeneic hematopoietic stem cell transplantation (HSCT) is limited by life-threatening complications such as severe or acute graft-versus-host disease (GVHD). Despite intensive prophylaxis with immunosuppressive agents, the incidence of GVHD occurs in 9-50% of patients undergoing transplant with an identical HLA sibling matched donor and 75% of patients undergoing unrelated HLA donors. AIM OF STUDY: To evaluate our experiences in GVHD prophylaxis and treatment after alloHSCT, GVHD incidence and prognostic factors and administration of new immunosuppressive regiments. Can we recognize clinical parameters which are associated with occurrence and severity of graft-versus-host disease? PATIENTS AND METHODS: Starting from September 2000 till September 2010, 63 patients (36 males and 27 females) at the age of 16-56 (median range 33 years) with hematological malignancies were treated with alloHSCT on Department of Hematology, Clinical Centre, Skopje. In 10 patients bone marrow was used as source of stem cells and in 53 patients stem cells were obtained from peripheral blood. From the group of 63 patients, 26 patients had active disease at the time of transplantation. GVHD prophylaxis was accomplished with combination of cyclosporine and methotrexate (Seattle regimen) or more intensive immunosuppression regiments. RESULTS: GVHD was noticed in 30 patients (47.6%) and in 33 patients (52.4%) a manifestation of GVHD was noticed. Acute GVHD was noticed in 24 patients (38%) and chronic GVHD in 20 patients (31.7%) The remaining 32 patients (45%) achieved complete clinical and hematological remission. Lethal outcome was confirmed in 31(49%) patients (9 from chrGVHD, 6 from acute GVHD, 16 from disease relapse). CONCLUSION: The incidence of acute GVHD in our study was 38% and 31% for chronic GVHD. The most common GVHD reaction was registered in female donors and male recipients, with higher GVHD incidence in elderly patients. In all patients stem cells were obtained from peripheral blood. Active disease, sex, source of hematopoietic cells, age and conditional regiments are the most significant predictive factors with the high incidence of GVHD.

Trends in acute leukaemia incidence in adults in the Republic of Macedonia (1993-2003)--a descriptive epidemiological study.

OBJECTIVE: To analyse trends in incidence rates of acute leukaemia in patients aged 15 and over admitted to hospital. DESIGN: A descriptive epidemiological study. SETTING: University teaching hospital, Haematology Clinic, Skopje. RESULTS: The crude incidence rates of acute leukaemia in adults during this period increased substantially (p for overall trend < 0.001). The lowest crude incidence rates (CIR) were observed in 1996 (CIR = 1.64/100 000; 95% Confidence Interval CI = 1.1-2.4), while the highest were noted in 2003 (CIR = 3.76/100 000; 95% CI = 2.9-4.8). In 1993 the sex ratio of the incidence rates (males to females) was Rate Ratio (RR) = 2.23, while as of 2001 the association between sexes disappeared (RR = 1). The trend in males was not significant (p = 0.160), while in females it showed a monotonic increase that was highly significant (p < 0.001). CONCLUSIONS: During a short period of time (11 years) we have noted an increase in the incidence rates of acute leukaemia in our population aged 15 years and above. The study suggests that this could be due to increased risk in females, and in adults over 40 years. In addition, according to the census results in 1994 and 2002 the proportion of people aged 65 and above increased by 30.5% implying that this demographic change could account for part of the relative increase in the incidence rates of acute leukaemia. Further analytic studies are needed to address the possible causes of these changes. What is already known on this topic: The risk of acute leukaemia increases by age and it is higher in males than in females. WHAT THIS STUDY ADDS: The incidence rates are equal between the sexes; the increase in risk of acute leukemia in females could be due to environmental risk factor.

CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders.

CTLA-4 is a CD28 homologue that plays an important role in negative regulation of T-cell responses. Its transient expression on the surface of activated T cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 50 patients with autoimmune hemolytic anemia (AIHA), of which 20 had idiopathic AIHA and 30 had AIHA and chronic lymphocytic leukemia (CLL), and in 60 patients with immune thrombocytopenic purpura (ITP). Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. The G allele was present at a significantly higher frequency among the patients with AIHA (P = 0.003), whereas no difference was observed between patients with ITP and controls. The G allele frequency was highest among CLL patients who had developed AIHA. The obtained data indicate that the G allele of CTLA-4 predisposes to the development of AIHA, particularly among patients with CLL.