The Prognosis of Adult Burkitt's Cell Leukemia in Real-Life Clinical Practice.

OBJECTIVE: Many studies reported an improved prognosis in patients with Burkitt's lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt's cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent allogeneic stem cell transplantation (ASCT) in their first remissions. MATERIALS AND METHODS: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups. RESULTS: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NT-ALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients. CONCLUSION: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma.

OBJECTIVE: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib. MATERIALS AND METHODS: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was "Robust Multi-array analysis" normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis. RESULTS: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways. CONCLUSION: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

Comparison of Myelodysplastic Syndrome Prognostic Scoring Systems.

OBJECTIVE: Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease. Patients are at risk of developing cytopenias or progression to acute myeloid leukemia. Different classifications and prognostic scoring systems have been developed. The aim of this study was to compare the different prognostic scoring systems. MATERIALS AND METHODS: One hundred and one patients who were diagnosed with primary MDS in 2003-2011 in a tertiary care university hospital's hematology department were included in the study. RESULTS: As the International Prognostic Scoring System (IPSS), World Health Organization Classification-Based Prognostic Scoring System (WPSS), MD Anderson Prognostic Scoring System (MPSS), and revised IPSS (IPSS-R) risk categories increased, leukemia-free survival and overall survival decreased (p<0.001). When the IPSS, WPSS, MPSS, and IPSS-R prognostic systems were compared by Cox regression analysis, the WPSS was the best in predicting leukemia-free survival (p<0.001), and the WPSS (p<0.001) and IPSS-R (p=0.037) were better in predicting overall survival. CONCLUSION: All 4 prognostic systems were successful in predicting overall survival and leukemia-free survival (p<0.001). The WPSS was found to be the best predictor for leukemia-free survival, while the WPSS and IPSS-R were found to be the best predictors for overall survival.

Common variable immune deficiency associated Hodgkin's lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report.

Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin's lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26×17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 µg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes for our patient inability to control his EBV infection which eventually lead to hemophagocytic lymphohistiocytosis. To conclude, rare simultaneous manifestation of primary immune deficiencies (PID), Hodgkin's lymphoma and EBV-HLH occurred in our patient which have concordant immunological mechanism that eventually lead poor prognosis in our patient.

Optimizing mobilization strategies in difficult-to-mobilize patients: The role of plerixafor.

Peripheral blood stem cell collection is currently the most widely used source for hematopoietic autologous transplantation. Several factors such as advanced age, previous chemotherapy, disease and marrow infiltration at the time of mobilization influence the efficacy of CD34(+) progenitor cell mobilization. Despite the safety and efficiency of the standard mobilization protocols (G-CSF ± chemotherapy), there is still a significant amount of mobilization failure rate (10-40%), which necessitate novel agents for effective mobilization. Plerixafor, is a novel agent, has been recently approved for mobilization of hematopoietic stem cells (HSCs). The combination of Plerixafor with G-CSF provides the collection of large numbers of stem cells in fewer apheresis sessions and can salvage those who fail with standard mobilization regimens. The development and optimization of practical algorithms for the use Plerixafor is crucial to make hematopoietic stem cell mobilization more efficient in a cost-effective way. This review is aimed at summarizing how to identify poor mobilizers, and define rational use of Plerixafor for planning mobilization in hard-to-mobilize patients.

Epidemiology and emerging resistance in bacterial bloodstream infections in patients with hematologic malignancies.

BACKGROUND: The objective of this study was determine the frequency of bloodstream infections (BSIs) and the causative bacteria and their resistance patterns in patients with hematological malignancies (HMs) in a large tertiary care university hospital in Turkey over a 5-year period. METHODS: A total of 2098 patients with HMs with 3703 neutropenic episodes were included. Patients were classified as high-risk (n = 843) and low-risk (n = 1255) groups and evaluated for frequency of BSIs, causative bacteria, and their resistance patterns. RESULTS: The frequency of BSIs was 14.5%. The frequency of gram-negative BSIs in high-risk and low-risk groups was 10.7% and 5.4% (p < 0.001), respectively. The frequency of gram-positive BSIs in high-risk and low-risk groups was 7.0% and 3.9% (p < 0.001), respectively. Gram-negative bacteria predominated (52.6%), with Escherichia coli (17.3%) and Klebsiella spp. (11.0%) as the most frequent organisms. Coagulase-negative staphylococci (10.4%) and Corynebacterium spp. (6.3%) were the most common gram-positive bacteria (35.8%). The rate of extended-spectrum beta-lactamase (ESBL) production was 45% for E. coli and 58% for Klebsiella spp. Quinolone resistance was 58% for E. coli and 11% for Klebsiella spp.. The overall frequency of ceftazidime resistance in Pseudomonas aeruginosa was 28%, and 87% of Acinetobacter spp. were multidrug-resistant. Of Staphylococcus aureus isolates, 24.8% were resistant to methicillin. CONCLUSION: The dominating causes of BSIs in patients with HMs in our hospital are resistant gram-negative bacteria, which has made empirical antimicrobial choice a highly challenging issue in this patient population.

Rebound Thrombocytosis following Induction Chemotherapy is an Independent Predictor of a Good Prognosis in Acute Myeloid Leukemia Patients Attaining First Complete Remission.

There are very few data about the relationship between acute myeloid leukemia (AML) prognosis and bone marrow recovery kinetics following chemotherapy. In this study, we aimed to assess the prognostic importance and clinical associations of neutrophil and platelet recovery rates and rebound thrombocytosis (RT) or neutrophilia (RN) in the postchemotherapy period for newly diagnosed AML patients. De novo AML patients diagnosed between October 2002 and December 2013 were evaluated retrospectively. One hundred patients were suitable for inclusion. Cox regression analysis using need for reinduction chemotherapy as a stratification parameter revealed RT as the only parameter predictive of OS, with borderline statistical significance (p = 0.06, OR = 7; 95% CI 0.92-53), and it was the only parameter predictive of DFS (p = 0.024, OR = 10; 95% CI 1.3-75). In order to understand whether RT or RN was related to a better marrow capacity or late consolidation, we considered neutrophil recovery time and platelet recovery time and nadir-first consolidation durations in all patients in the cohort. Both the marrow recovery duration and the time between marrow aplasia and first consolidation were shorter in RT and RN patients. To our knowledge, this is the first study to report a correlation between RT/RN and prognosis in AML.

Vitamin D status and its association with gradual decline in cognitive function.

BACKGROUND/AIM: To compare plasma vitamin D concentrations among patients with normal cognitive function (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). MATERIALS AND METHODS: In total, 158 patients with AD, 228 patients with MCI, and 603 control subjects were included. Plasma levels of 25-hydroxyvitamin D were measured after comprehensive geriatric assessment and compared among groups. SPSS 15.0 was used for statistical analysis. RESULTS: Mean levels of 25-hydroxyvitamin D were significantly different among the 3 groups of AD patients, MCI patients, and controls (P < 0.001). Post hoc analysis revealed that the levels were significantly lower in the MCI group than the control group (P = 0.002) and significantly lower in the AD group than the control group (P = 0.003). Multivariate analysis showed that age (OR: 1.070, 95% CI: 1.025-1.116, P = 0.002), instrumental activities of daily living score (OR: 0.920, 95% CI: 0.850-0.995, P = 0.037), 25-hydroxyvitamin D level (OR: 0.959, 95% CI: 0.932-0.987, P = 0.004), and diabetes mellitus (OR: 2.476, 95% CI: 1.153-5.319, P = 0.020) were factors independently associated with AD. CONCLUSION: This study demonstrated that there is a correction between plasma 25-hydroxyvitamin D levels and cognitive functions.

Clinicopathological associations of acquired erythroblastopenia.

INTRODUCTION: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. BACKGROUND: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. MATERIAL AND METHOD: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. RESULTS: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). DISCUSSION: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. CONCLUSION: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated.

The factors affecting early death after the initial therapy of acute myeloid leukemia.

There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML.

Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load.

AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg­patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Inoperable isolated cardiac hydatid cyst controlled with albendazole in an older adult with dementia.

Hydatid cyst, a human parasitic disease, remains a clinical problem in undeveloped and developing countries. Although liver and lungs are regular sites of infection, rarely other organs such as the heart can be involved. Herein, we report an isolated cardiac hydatid cyst in an 87-year-old man. He had a history of dementia for 5 years and no history for cardiac or pulmonary disease. He presented with exertional dyspnoea which continued up to 6 months. The diagnosis was made by echocardiography and computed tomography (CT). The patient was inoperable and was treated with albendazole 10 mg/kg for 6 months. After a 6-month follow-up, echocardiography revealed reduction in the size of the cyst. We believe this is the first documented case of cardiac hydatid cyst which regressed with only medical treatment in an older adult with dementia.

A confusing case: pulmonary lesions including cavities, isolated left heart endocarditis and inferior vena cava thrombosis in a patient with perforated diverticulitis.

There are numerous causes of pulmonary cavitary lesions as infection (bacterial, parasitic and invasive fungal), Wegener granulomatosis (WG) and other vasculitis, sarcoidosis, malignancy, septic thromboembolism, airways disease (cystic bronchiectasis and bullae), pneumatoceles and traumatic parenchymal laceration. Herein, we present a case with perforated diverticulitis causing pulmonary cavitary lesions and a septic thrombus in the neighboring inferior vena cava.

Triple DMARD combination for rheumatoid arthritis resistant to methotrexate and steroid combination: a single-center experience.

The mainstay of RA treatment is the disease-modifying antirheumatic drugs, and triple DMARD combination is now known to be better than monotherapies. Our aim in this trial was to report our clinical experience with triple DMARD therapy for resistant rheumatoid arthritis. Data of 140 patients with RA resistant to methotrexate and steroid combination were evaluated retrospectively. One hundred and nineteen (85 %) were female, and the median age at diagnosis was 56 (29-82) years. The median time between the diagnosis and beginning of triple therapy was 45.5 (6-564) months. Fifty-two (37.1 %) patients (group 1) on triple therapy protocol achieved remission, but the others (88; 62.9 %) (group 2) did not. The mean DAS28 scores for the study group before triple DMARD therapy and after 12 months under triple DMARD therapy were 4.93 and 3.24, respectively. The DAS28 scores after 12 months for groups 1 and 2 were 2.57 and 3.64. The median follow-up period for patients in group 1 was 60 months (23-118), and the mean DAS28 score at the time of the analysis for group 1 was 2.36. Triple DMARD combination may save one-third of the MTX-resistant RA patients from the serious side effects and the cost of anti-TNF.

The evaluation of neutrophil-lymphocyte ratio in Alzheimer's disease.

BACKGROUND/AIM: There is growing consensus in the literature that inflammation plays a significant role in the pathophysiology of Alzheimer's disease (AD). The blood neutrophil-lymphocyte ratio (NLR) is a new, inexpensive and easily applicable marker of inflammation. The aim of this study was to investigate the association between NLR, as an inflammatory biomarker, and AD. METHODS: 241 AD patients and 175 patients with normal cognitive function were evaluated in this study. RESULTS: The mean ± SD NLR of AD patients was significantly higher than that of patients with normal cognitive function (3.21 ± 1.35 vs. 2.07 ± 0.74, p < 0.001, respectively). Receiver operating characteristic curve analysis suggested that the optimum NLR cutoff point for AD was 2.48 with 69.29% sensitivity, 79.43% specificity, 82.30% positive predictive values and 65.30% negative predictive values. Logistic regression analysis showed that elevated NLR (OR: 4.774, 95% CI: 2.821-8.076, p < 0.001) was an independent variable for predicting AD. CONCLUSION: Elderly people with AD have higher NLR than healthy controls. Elevated NLR levels are usually considered as an inflammatory marker. The results of this study suggested that inflammation plays a role in the pathogenesis of AD.