Ozan Salim

Array comparative genomic hybridization analysis of adult acute leukemia patients.

We have performed a retrospective array-based comparative hybridization (array-CGH) study on 41 acute leukemia samples [n=17 acute lymphoblastic leukemia (ALL) patients only at diagnosis, n=3 ALL patients both at diagnosis and relapse; n=20 acute myeloid leukemia (AML) patients only at diagnosis and n=1 AML patient both at diagnosis and relapse] using an Agilent 44K array. In addition to previously detected cytogenetic aberrations, we observed cryptic aberrations in 95% of ALL and 90.5% of AML cases. ALL-specific recurrent abnormalities were RB1 (n=3), PAX5 (n=4), and CDKN2B (n=3) deletions; AML-specific recurrent abnormalities were HOXA9 and HOXA10 (n=2) deletions and NOTCH1 duplication (n=2). Recurrent duplication of the ELK1 oncogene was observed in both ALL (n=2) and AML (n=3) cases. Our results demonstrate that oligo-array CGH (oaCGH) is an effective method for defining copy number alterations and identification of novel recurring unbalanced abnormalities. At least for now, however, the use of oaCGH for routine diagnosis still has some restrictions.

The association between endothelial dysfunction and hypertensive retinopathy in essential hypertension

Background Endothelial dysfunction, which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between pro-inflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. Numerous experimental and clinical reports suggest that a high von Willebrand factor (vWF) level reflects endothelial damage or dysfunction. Hypertensive retinopathy (HR) is a condition characterized by a spectrum of retinal vascular signs in people with elevated blood pressure. The pathophysiological mechanism of HR is not completely understood. Elevated blood pressure alone does not fully account for the extent of retinopathy. Endothelial dysfunction and mechanisms known to be involved in vascular lesions may be involved in the pathophysiological mechanism of HR. Therefore, this study was designed to answer the following questions: (i) Do vWf levels change in HR? and (ii) Is there any relation between degree of HR and vWf levels? Material/Methods This study included 80 hypertensive patients with HR. Group 1 comprised 40 patients with grade I HR, and group 2 comprised 40 patients with grade II HR. We selected 40 healthy subjects for the control group. Results Level of vWf in group 2 was significantly higher than in group 1 (p=0.017) and the control group (p<0.001), and it was also higher in group 1 than in the control group (p<0.005). Also, vWf showed positive correlation with degree of HR in the hypertensive group (r=0.284, p=0.009) Conclusions Our study suggests that endothelial dysfunction, which is a mechanism known to be involved in vascular lesions, may promote the development of HR.

Azacitidine versus decitabine in patients with refractory anemia with excess blast—Results of multicenter study

The present study aimed to compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndrome (MDS). A total of 88 patients diagnosed with refractory anemia with excess blast (RAEB) treated with azacitidine (n=57) or decitabine (n=31) were evaluated. Comparisons between azacitidine and decitabine groups were performed in the whole cohort, and in a 1:1 propensity score-matched cohort in order to reduce the simple selection bias. Patients who received azacitidine or decitabine had comparable overall response rates in both the unmatched (49.1% vs. 64.5%, p=0.166) and the propensity-matched cohorts (52% vs. 68%, p=0.248). The cumulative incidence of AML transformation at one year was comparable between azacitidine and decitabine in the unmatched (24.0% vs. 31.3%, p=0.26) and in the propensity-matched cohorts (18.7% vs. 31.5%, p=0.11). There was no difference in terms of transfusion requirement, febrile neutropenia episodes or the need for antifungal use during the treatment cycles in the propensity-matched cohort. The median overall survival was 20.4 months for azacitidine and 16.8 months for decitabine (p=0.59). Finally, we found that at least a four-cycle treatment with any HMA was a favorable factor. In conclusion, both azacitidine and decitabine have similar efficacy and toxicity profiles in the treatment of MDS-RAEB.

Seasonal Association of Immune Thrombocytopenia in Adults

BACKGROUND Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. AIMS We investigated whether months and/or seasons have triggering roles in adults with ITP. STUDY DESIGN Descriptive study. METHODS A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. RESULTS The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). CONCLUSION This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.

Consideration of difficulties and exit strategies in a case of face allotransplantation resulting in failure

We describe the first rescue procedure in a case of total face allotransplantation. The recipient was a 54‐year‐old man with severe disfigurement of the entire face following an accidental gunshot injury 5 years previously. The large defect included the maxilla, mandible, and mid‐face. Full face procurement was performed from a multiorgan cadaveric donor and was allotransplanted to the recipient. The post‐transplant induction immunosuppressive regimen included ATG combined with tacrolimus, mycophenolate mofetil, and prednisone, while maintenance was provided by the last three of these. Although the early postoperative period was uneventful, squamous cell carcinoma developed in the upper and lower extremities in the fifth postoperative month, and post‐transplant lymphoproliferative disorder (PTLD) occurred in the sixth month postoperatively. Malignancies were treated, involving both surgical and medical approaches. The patient developed opportunistic pulmonary and cerebellar aspergillosis. In order to reduce the adverse affects and metabolic and immunological load, the transplanted face was removed and replaced with a free flap. Although the early postoperative period was promising, with the transferred flap surviving totally and all vital signs and general status appearing to be improving, the patient was eventually lost due to complicated infectious and metabolic events. Although this case was unsuccessful, we suggest that the immunological and metabolic load should be reduced as soon as stable medical conditions are established in case of diagnosis of a situation involving a high rate of mortality, such as PTLD and untreatable opportunistic infections. This should include withdrawal of all immunosuppressive drugs and removal of all allotransplanted tissues.

The Role of Azacitidine in the Treatment of Elderly Patients with Acute Myeloid Leukemia: Results of a Retrospective Multicenter Study

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts. Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years o ld who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included. Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%. Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment. Median overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact. Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

Cutaneous thrombosis as the presenting finding of paroxysmal nocturnal haemoglobinuria

A 24-year-old woman with a previous history of sagittal vein thrombosis and a 5-year history of Budd–Chiari syndrome had been treated by anticoagulation and insertion of a transjugular intrahepatic portosystemic shunt. She presented to our emergency department with the recent onset of a painful skin rash following a nonspecific febrile illness (top). Inherited thrombophilia and disseminated intravascular coagulation were ruled out. A normocytic anaemia without schistocytes and a mild thrombocytopenia were detected. Blood and urine cultures were negative. Urinalysis showed urobilinogenuria without haemoglobinuria. Lactate dehydrogenase activity was twice normal. Screening for a paroxysmal nocturnal haemoglobinuria (PNH) clone was performed by multiparameter flow cytometry for CD14, CD15, CD24, CD64 and FLAER (fluorescein-labelled proaerolysin): 98% of both neutrophils and monocytes were abnormal. Skin biopsy showed fibrin thrombi in the capillaries, necrosis and haemorrhagic infarction (bottom). A diagnosis of cutaneous thrombosis secondary to PNH was made. She was treated empirically with antibiotics, methylprednisolone and low molecular weight heparin. However, some of the lesions expanded and ulcerated. After compassionate use approval, four doses of eculizumab were given. Despite this therapy, she remained prothrombotic over the next weeks and portal vein thrombosis developed. Unfortunately, she died due to sepsis, secondary to skin ulceration, and liver failure.

Langerhans Cell Histiocytosis: A Diagnostic Challenge in the Oral Cavity

Background Langerhans cell histiocytosis (LCH) is a rare disorder of the reticuloendothelial system with unknown etiology. This report aims to present a case of LCH with diffuse involvement of the oral cavity and to raise awareness of the distinguishing features of this diagnostically challenging entity. Case Report A 26-year-old male patient presented with complaints of teeth mobility, intense pain, and difficulty in chewing. Intraoral and radiological examinations revealed generalized gingival hyperplasia and severe teeth mobility with widespread alveolar bone loss. Periodontal therapy was performed with no significant improvement. An incisional biopsy revealed Langerhans cells and positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids. Regression of gingival lesions, as well as significant decrease in mobility of the remaining teeth and severity of pain, was achieved during 12 months of follow-up. Conclusion The rarity and variable system involvement of LCH necessitate a multidisciplinary approach be carried out for accurate diagnosis, effective treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH may aid clinicians greatly in reducing morbidity and mortality associated with this debilitating condition.

C-MYC and BCL2 translocation frequency in diffuse large B-cell lymphomas: A study of 97 patients.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. MYC and BCL2 rearrangements have been reported in a proportion of DLBCLs, where they may be associated with an adverse clinical outcome. The aim of this study was to determine the frequency of MYC and BCL2 translocations in DLBCL and assess the prognostic impact in DLBCL patients. Materials and Methods:   In the present study, we evaluated the expression patterns of CD 10, BCL6, and MUM 1 by immunohistochemistry in 121 cases with DLBCL in tissue microarray (TMA): 62 cases in germinal center B-cells (GCBs); and 59 cases in activated B-cells (ABCs) of which 60 were females and 61 were males. MYC and BCL2 rearrangements were investigated by interphase fluorescence in situ hybridization on TMAs in 97 DLBCLs. Result: MYC rearrangements were observed in 11 of 97 cases. There was no association with other clinical features, including age, sex, and nodal/extranodal disease. MYC rearrangement was associated with significantly worse overall survival (P < 0.01). BCL2 rearrangements were observed in 14 of 97 cases. There was no association with other clinical features including age and sex. BCL2 rearrangement had a worse outcome (P < 0.01). MYC and BCL2 rearrangements were observed in 3 of 97 cases with the age of  53 (female), 53, 63 years old, respectively, died in 24, 18, and 35 months after the diagnosis. Two cases had primary nodal and one case primary extranodal presentations. All these patients had stage IV disease. Conclusion: We concluded that C-MYC and BCL2 may contribute to aggressive transformation, and more mechanism-based therapy should be explored. Targeted therapies involving these rearrangements and its associated pathways may change the fate of DLBCLs. Analysis of MYC gene rearrangement along with BCL2 is critical in the identification of high-risk patients with poor prognosis.

Previously Unreported Chromosomal Aberrations of t(3;3)(q29;q23), t(4;11)(q21;q23), and t(11;18)(q10;q10) in a Patient with Accelerated Phase Ph+ CML.

Chronic myelogenous leukemia (CML) is a clonal hematological disorder, which is characterized by the presence of the classical or variant Philadelphia translocations. During the progression to blastic phase of the disease secondary chromosomal abnormalities may emerge. Such secondary chromosomal abnormalities are nonrandom, the more frequent ones being trisomy 8 and 19, supernumerary i(17q), and extra Philadelphia chromosomes. Furthermore, a minor percentage of the patients may acquire different secondary chromosomal abnormalities including translocations between other chromosomes. We report here a patient with Ph+ CML presenting secondary chromosomal abnormalities including t(4;11)(q21;q23), t(3;3)(q29;q23) and t(11;18)(q10;q10) during the course of CML progression.