Neutropenic enterocolitis (NE) or typhlitis is a serious complication of anticancer therapy, especially in he- matological malignancies. We describe a case of acute lymphoid leukemia presenting the early onset of a syndrome with the clinical features and specific radiological findings of NE during the neutropenic phase.
Antiphospholipid syndrome (APS) is an autoimmune disease characterised by recurrent arterial or venous thrombosis, pregnancy morbidity and the persistence of positive antiphospholipid antibodies (aPLA). The selectins are cell adhesion molecules that mediate the interaction among leukocytes, activated platelets and endothelial cells. P-selectin, which can be identified as soluble form in plasma, intercedes the attachment and rolling of leukocytes on activated endothelial cells, and is involved in the recruitment of leukocytes to thrombi.
Objectives
We aimed to investigate whether P-selectin polymorphisms are associated with thrombosis in patients with APS.
Methods
Fourty adult patients with APS and 40 healthy subjects as controls with no history of thrombosis or autoimmune diseases were included into the study. The diagnosis and classification of APS were based on the report of an international workshop. The subjects participating in the study had no systemic lupus erythematosus and the risk factor such as hypertension or hyperlipidemia for thrombosis. Genomic DNA was extracted from citrated blood samples of all subjects. Three single nucleotide polymorphisms associated with P-selectin coding region (S290N, c.1087G>A; D562N, c.1902G>A; T715P, c.2363A>C) were assessed.
Results
There were 26 APS (65%) patients with thrombosis involved vein, artery, vein and artery together respectively; 12 (46%), 10 (38%) and 4 (15%). The number of patients without thrombosis was 14 (35%). The mean age of patients (92% female) was 39,4±9,5. The frequency of D562N-DN genotype was significantly higher in patients with APS than healthy controls (p: 0,003). The frequency of this genotype was significantly higher in patients with APS with thrombosis compared with patients with no thrombosis (p:0,03). D562N-NN genotype was found at a higher frequency in patients with APS than healthy controls (p:0,004). The frequency of D562N-NN genotype was comparable between patients without thrombosis and controls (p:0,21). On the other hand, S290N and T715P polymorphisms were similar in all subjects (Table). No relationship was found between APLA, thrombocytopenia or fetal loss and P selectin polymorphisms.
Conclusions
Our results suggest that D562N polymorphism DN genotype of P-selectin is associated with an increased risk of thrombosis in patients with APS. NN genotype of the same polymorphism might be protective for thrombosis in those patients. The effect of D562N polymorphism on soluble P-selectin levels will be studied in the next step.
e22049 Background: Inherited factors such as factor V Leiden (FVL), prothrombin G20210A (PT) mutations and psgl-1 vntr polymorphism (PSGL-1 VNTR) are shown to be related with venous thromboembolism (VTE). Factors assumed acquired with carcinogenesis like tissue factor (TF) and soluble p-selectin (sP-selectin) are also shown to be related with venous thromboembolism (VTE).We evaluated inherited factors and factors assumed acquired with carcinogenesis such as tissue factor (TF) and soluble p-selectin (sP-selectin) in cancer patients with adenocarcinoma. Methods: This is a retrospective observational study held with patients followed by Istanbul Bilim University Department of Medical Oncology between October 2007 and March 2012. Of 1,838 patients 63 (3.4%) with adenocarcinoma histology, experienced VTE. The diagnosis of VTE was confirmed by radiology and the patients were treated accordingly. We defined VTE by sites as deep venous thrombosis (DVT), pulmonary embolism (PE), other vascular territories (subclavian, jugular and pelvic veins), and central venous catheter related (CVC-R). Blood drawn at any time, during active treatment or follow-up, at any stage with VTE (n=63) and without VTE (n=38) as a control grup.This study is approved by Istanbul Bilim University Ethics Commitee. Results: Results were shown at table. sP-selectin levels were higher at patients with thrombosis (p=0.036). PSGL-1 VNTR polymorfism was related with site of thrombosis. AB and AC types were more frequent in patients with CVC-R and other vein thrombosis (p=0.02). Besides heterozygosity (AB+AC) relationship was more prominent in this group (p=0.007). Tissue factor was higher at pancreatic carcinoma than the others. (800 (16-800) vs 99 (13-800); p=0.047). Conclusions: Although this is a retrospective observational study held with blood samples delivered randomly,we confirmed the data regarding the levels of TF and sP-selectin were higher in thrombosis. It is shown for the first time that a relationship between PSGL-1 VNTR polymorfism and sites of VTE, of which is unknown with clinical relevance.
Factor VIII:C, epsilon amino-caproic acid or tranexamic acid are prophylactic agents used in preventing hemorrhage pre-operatively in patients with hemophilia A. Although hemophilia A seems to be a factor that avoids the development of acute myocardial infarction (AMI) as it tends to be associated with increased bleeding, it should be kept in mind that prothrombotic agents used pre-operatively for prophylaxis may increase the risk for AMI in the presence of the factor V Leiden mutation. In this report, we discuss the development of AMI following the use of recombinant factor VIII and tranexamic acid for prophylaxis in a patient with known hemophilia before a tooth extraction in conjunction with the relevant literature.
Background Activated factor XIII (FXIII) cross-links between fibrin monomers, thus increasing the clot stability and resistance to fibrinolysis. Congenital FXIII deficiency causes severe bleeding diathesis. Recently, a common polymorphism of the FXIII A subunit (FXIII Val34Leu) has been identified as a protective factor against both arterial and venous thrombosis. The aim of this study was to investigate the role of FXIII Val34Leu polymorphism in coronary artery thrombosis, especially in young patients. Methods and Results One hundred and thirty patients under than 60 years of age with a history of myocardial infarction (%) and 130 healthy control subjects in the same age group were included to our study. Genomic DNA was extracted from venous blood samples and the polymerase chain reaction method was used to genotype FXIII Val34Leu polymorphism. Coronary risk factors such as obesity, diabetes mellitus, hyperlipidemia and smoking were compared between the groups with chi-square test and logistic regression analysis. The Leu allele frequency was significantly lower in patient group compared to control group (7.69% vs 19.23%, p=0.0001, chi-square). This difference was extremely significant in patients younger than 50 years-old (5.26% vs 19.64%, p<0.0001, chi-square). Conclusion Our findings support the hypothesis that Val34Leu polymorphism in FXIII gene has a protective effect against myocardial infarction. (Circ J 2006; 70: 239 - 242)
The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies.In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA), 62 patients with immune thrombocytopenic purpura (ITP), and 150 healthy individuals.Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL) patients with AIHA (n=4), all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG). There was no significant statistical association between G allele and systemic lupus erythematosus (SLE) or AIHA.These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.AMAÇ: Sitotoksik T lenfosit antijen-4 (CTLA-4) ifadesi T lenfositlerde gerçekleşir ve T hücre cevabını engeller. Hayvan modellerinde CTLA-4 yokluğunun, dokuların poliklonal çoğalan lenfositler tarafından yoğun infiltrasyonu nedeni ile, ölümcül olduğu gösterilmiştir. Farklı otoimmün hastalıklar ile ilişkilendirilmiş CTLA-4 A49G polimorfizminin, CTLA-4 molekülünün inhibitör fonksiyonunu azalttığı düşünülmektedir. YÖNTEMLER: Bu çalışmada otoimmun hemolitik anemi (OIHA) hastası 46 kişi, immun trombositopenik purpura (ITP) hastası 62 kişi ve 150 sağlıklı kontrol bireyinde CTLA-4 A49G polimorfizmi çalışılmıştır.ITP ve OIHA hastalarından oluşan iki grupta da sağlıklı kontrol bireyleri ile karşılaştırıldığında benzer allel frekansları ve genotip dağılımları saptanmıştır. Alt grup analizi gerçekleştirildiğinde ise hem OIHA hem de KLL hastalığına sahip 4 bireyin hepsinin polimorfizme sahip olduğu gösterilmiştir (3 AG, 1 GG). Risk alleli olan G OIHA, İTP ve kontrol grubunda incelendiğinde istatistik olarak anlamlı bir farklılık saptanmamıştır. SONUÇ: Bu verilerin ışığında CTLA-4 A49G polimorfizminin lenfoproliferatif hastalıkların patogenezine bir katkısının olmadığı veya lenfoproliferatif hastalığa sahip bireylerde otoimmün komplikasyonların gelişmesi açısından risk oluşturmadığı sonucuna varılmıştır.
Currently allogeneic hematopoietic stem cell transplantation (alloHSCT) is still the only curative option in intermediate and high risk AML and majority of ALL patients. Though we have many published data for retrospective analysis of ility registry data, single center's experience is still worth for looking working in high output and reporting consequently. Donor availability is not a big obstacle since introduction of haploidentical related donor transplants and T cell replete BM/PBSC use with post infusion Cy approach. Between 2011-2016 our center performed 161 alloHSCT (107 matched related, 29 unrelated and 25 haplo) for acute leukemia (AL) patients. Conditioning regimen were ablative, stem cell source was peripheral blood SC (exc. Haplos) and haplo approach was T cell replete post infusion Cy. Here we comparatively report our AML and ALL patients who are in CR1 or CR2 at the time of transplantation. We selected all our patients beyond day 100 and who received only single alloHSCT. Ninty-two (67%) AML and 46 (33%) ALL total of 138 patients were eligible for analysis. The median follow-up times for AML and ALL were, 3-56 mo.s and 3-49 mo.s respectively. The cumulative results for OS are shown in Table 1 segregated for donor type. All groups showed statistically similar follow up and OS. In K-M curves using log-rank analysis for comparison of related vs MUD vs haplo in acute leukemias (Figure 1), ALL (Figure 2) and AML (Figure 3) we did not observe any siginificant survival difference (P > .05). None of the groups reached median OS in 2 years of f/u. After 2 years DFS is 69.5% for AML and 65% for ALL. Our single center homogeneous centralized data clearly shows that allogeneic HSCT, whatever the donor origin is reaches an OS rate of >60% after 2 years. As we are able to find a donor for 95% of the patients by the increasing rise of haplo SCTs, all non-low risk acute leukemia patients in controlled disease status should be referred to experienced HSCT centers for allogeneic HSCT. Use of alternative donor's has no negative impact on OS and relapse rate, in acute leukemia patients in remission.Table 1Overal Survival According Different Donor GroupsMatched Related DonorMatched Unrelated Donor 9/10-10/10Haploidentical Related DonorTOTALF/U28 mo (10-56)17 mo (3-49)12 mo (3-36)OS100d1 Year100d1 Year100d1 Year100d1 YearAML64/6852/6812/1311/1310/118/1186/9271/9294%76%92%84%91%73%93%77%F/U26 mo (3-57)23 (13-29)13 mo(4-34)ALL24/2617/269/107/109/108/1042/4632/4692%65%90%70%90%80%91%70% Open table in a new tab Figure 2K-M Curve OS, ALL Patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3K-M Curve OS, AML Patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)
