Aleksandar Savic

Recombinant factor VIIa analog in the management of hemophilia with inhibitors: results from a multicenter, randomized, controlled trial of vatreptacog alfa

Vatreptacog alfa, a recombinant factor VIIa (rFVIIa) analog with three amino acid substitutions and 99% identity to native FVIIa, was developed to improve the treatment of hemophilic patients with inhibitors.

The hematopoietic cell transplantation comorbidity index is a predictor of early death and survival in adult acute myeloid leukemia patients.

The hematopoietic cell transplantation comorbidity index (HCT-CI) is predictive of early death and survival in elderly patients with acute myeloid leukemia (AML). The aim of this study was to determine the prognostic role of the HCT-CI for early death and survival in adult AML patients. In the single-center retrospective study, we analyzed the outcome of 233 adult AML patients. The results indicated that the HCT-CI score is an independent predictor of early death in entire cohort of adult patients with AML. In subgroup analysis, HCT-CI is an independent predictor for early death in elderly patients but not in patients younger than 60 years. A high HCT-CI score predicts shorter survival in adult patients with AML.

Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity.

Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double‐blind, crossover, confirmatory phase III trial (adept™2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti‐drug antibodies (ADAs) to vatreptacog alfa.

Angiogenesis and Survival in Patients with Myelodysplastic Syndrome

Angiogenesis has been implicated in the pathogenesis and prognosis of myelodysplastic syndrome (MDS). In this study, we investigated the relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, common morphological and clinical factors, and survival in patients with MDS. We examined the MVD of paraffin-embedded bone marrow sections from 70 MDS patients and 31 controls. VEGF expression was determined in 50 patients and 20 controls. The median MVD in MDS patients was significantly higher than that in controls (p = 0.025), whereas there was no difference in VEGF expression between MDS patients and controls. In univariate analysis, increased MVD was associated with a shorter survival time (p = 0.023). However, in multivariate analysis, MVD was not an independent predictor of survival. The VEGF expression did not influence survival in univariate analysis. Survival was independently influenced by platelet count (p = 0.0073), cytogenetic risk category (p = 0.022), and transfusion dependence (p = 0.0073). Neither MVD nor VEGF expression were predictors for progression to acute myeloid leukemia in univariate analysis. Progression to acute myeloid leukemia was independently influenced only by the cytogenetic risk category (p = 0.022). This study confirmed increased MVD in MDS. It does not support an independent prognostic role of angiogenesis in MDS.

Prognostic impact of a suboptimal number of analyzed metaphases in normal karyotype lower-risk MDS

Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20-25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions.

Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis-associated severe aplastic anemia

Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery.

Early platelet count kinetics has prognostic value in lower-risk myelodysplastic syndromes

Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark - count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10-4), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively (P < 10-4). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860.

A case of essential thrombocythemia and ankylosing spondylitis treated with a combination of anagrelide, disease-modifying antirheumatic drugs, and etanercept.

INTRODUCTION A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis. CASE OUTLINE We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF-α antagonist). Both diseases were gradually brought under control. CONCLUSION Our case of ankylosing spondylitis and essential thrombocythemia suggests that concomitant etanercept and anagrelide therapy is safe, as well as effective.

A Case of Chronic Lymphocytic Leukaemia Occurring During Treatment of Chronic Myeloid Leukaemia

Chronic myeloid leukaemia (CML) and chronic lymphocytic leukaemia (CLL) are the most common types of leukaemia in elderly. The characteristic of CML is Philadelphia chromosome, became of translocation of chromosome 9 and 22 and fusion of bcr-abl gene. Result of fusion bcr-abl gene is activation tyrosin-kinase and uncontrolled proliferation of myeloid cells [1]. CLL characteristics are low proliferative activity and accumulation of monoclonal B lymphocytes in bone marrow, lymph nodes and other organs which are resistant to apoptosis. Simultaneous occurrence of CML and CLL is extremely rare. We report here a case of patient in whom CLL developed during the treatment of CML with imatinib mesilate.

Massive right-sided colon diverticular bleeding complicated by the transfusion related acute lung injury (TRALI)

Colonic diverticulosis is a condition which causes extensive bleeding of the lower gastrointestine in 40–50% of cases. In particular, right-sided diverticulosis, although uncommon requires lifesaving colectomy. Transfusion related acute lung injury (TRALI) is a transfusion reaction, which can occur after administration of various blood products. Although life threatening, it can be completely reversed usually within 72 to 96 hours. Here, we report a case of a young Caucasian male hospitalized due to severe anemia, hematochezia and extensive blood loss, all due to lower gastrointestinal hemorrhage from right-sided diverticulosis. These conditions were overlooked endoscopically and diagnosed then treated surgically with the right-sided hemicolectomy. During postoperative course, four hours after the last transfusion, patient developed fever, hypoxia and noncardiogenic pulmonary oedema, but made complete recovery through aggressive oxygen support within 96 hours. The aim of this case was to review current literature, to draw attention to a serious and under-diagnosed transfusion reaction, as well as discuss possible explanations for the diagnostic difficulties that occurred in this case.