Prognostic significance of bone marrow fibrosis in diffuse large B-cell lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas. The aim of this study is to determine the relationship between the increase in the degree of fibrosis in the bone marrow and prognosis and mortality in newly diagnosed DLBCL. METHODS: Bone marrow biopsy of 153 newly diagnosed DLBCL patients was determined by staining with reticulin, Masson's trichrome histochemical stain, and the degree of fibrosis was determined. RESULTS: In the bone marrow biopsy performed at the time of diagnosis, bone marrow fibrosis (BMF) was observed in 70 patients. While BMF-1 was detected in 42 patients (60%), BMF-2 was detected in 25 patients (35%) and BMF-3 was detected in 3 patients (4%). As the degree of BMF increased, the median overall survival and median progression-free survival times were significantly shorter (p: 0.008), (p < 0.001). In patients with an increased degree of BMF, a significant decrease in leukocyte and neutrophil counts was observed after chemotherapy (p: 0.004). According to the results of the multivariate Cox regression model, it was determined that high NCCN-IPI risk (HR: 8.25; %95 CI: 1.09-62.52; p = 0.041) and being BMF ≥ 2 (HR: 3.75; %95 CI: 1.65-8.51; p = 0.002), increased the risk of death (p = 0.002, -2 loglikelihood = 392,553). CONCLUSION: When the literature was reviewed, it was seen that this study was the first to define that bone marrow fibrosis grade 2 and above in DLBCL is a prognostic marker associated with worse survival. In the bone marrow pathology, which is examined to detect advanced disease in DLBCL, besides lymphomatous involvement, the detection of fibrosis grade is very important.

A different perspective on PET/CT before treatment in patients with Hodgkin lymphoma: importance of volumetric and dissemination parameters.

The aim of this study is to investigate the role of the combination of volumetric and dissemination parameters obtained from pretreatment 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the interim response and progression status in patients with Hodgkin lymphoma (HL). Pretreatment PET/CT images of HL patients were analyzed with LIFEx software, and volumes of interest (VOIs) were drawn with a fixed SUV 4.0 threshold. MTV, SUVmax, and TLG values were obtained from each VOI. Total MTV (tMTV) was calculated by summing the MTV values in all VOIs, and similarly, total TLG (tTLG) was obtained by summing the TLG values. The distance between the centers of the lesions was noted as Dmax, and the distance between the outermost voxels of the lesions as DmaxVox. tMTV/DmaxVox was calculated by dividing the tMTV value by the DmaxVox value, and tTLG/DmaxVox was calculated by dividing the tTLG value by the DmaxVox value. The correlation of pretreatment PET parameters with response groups (complete/poor) and relapse/progression status (stable/progressive) was statistically evaluated. A total of 52 patients were included in the study. Bulky disease, tMTV, tTLG, and tMTV/DmaxVox values were found to be significantly higher in the poor response group. tMTV > 190.60 ml was found to be the only prognostic factor predicting interim PET response. The tMTV/DmaxVox and tTLG/DmaxVox showed statistically significant differences between the groups with and without progression. tMTV/DmaxVox > 7.70 was found to be the only prognostic factor in predicting relapse/progression. The evaluation of tumor burden and dissemination together in 18F-FDG PET/CT before treatment in patients with HL can help us to predict the results of the patients.

The effect of haemoglobin, albumin, lymphocyte and platelet score on the prognosis in patients with multiple myeloma.

INTRODUCTION: In multiple myeloma cases, a variety of prognostic parameters have been identified, which contain the Durie-Salmon classification and the international staging system (ISS) that takes the serum ß2 microglobulin and albumin levels, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). This study investigates the effect of haemoglobin, albumin, lymphocyte and platelet (HALP) score which is a marker of inflammation status and nutrition, at the time of diagnosis for the patients with multiple myeloma on prognosis. METHODS: A total of 200 multiple myeloma patients with HALP scores calculated from serum haemoglobin, albumin, lymphocyte count and platelet levels at the time of diagnosis were retrospectively examined. The effect of HALP score on overall survival (OS) and progression-free survival and its relationship between the previously evaluated prognostic parameters were investigated. RESULTS: The optimal cut-off value with the ROC curves for the HALP score was 28.8. The patients were divided into two groups according to the optimal value of the HALP score (low-score group: HALP ≤28.8 [n: 134] and high-score group HALP >28.8 [n: 66]). In the group with the high HALP score, the OS was statistically longer than the low HALP score group (84 months and 53 months; p = 0.0001). In addition, when the effects of NLR, PLR, HALP score and ISS stage on OS were examined by multivariate analysis, all these markers were found to be statistically significant predictors. CONCLUSIONS: HALP score may be a valuable prognostic marker for patients with multiple myeloma.

Determination of the relationship between mortality and SOFA, qSOFA, MASCC scores in febrile neutropenic patients monitored in the intensive care unit.

PURPOSE: Febrile neutropenia (FN) is a hematological emergency. It is challenging and confusing for the clinicians to make the decision of the febrile neutropenic patients under chemotherapy to be monitored at intensive care unit (ICU). The aim of this study was to define the factors supporting decision-making for the critical patients with febrile neutropenia. METHODS: The data of 60 patients, who were taken to the ICU while they were under treatment in the Hematology Clinic with a diagnosis of febrile neutropenia, were analyzed retrospectively, in order to identify clinically useful prognostic parameters. RESULTS: The ICU mortality rate was 80%. Mortality was significantly associated with higher sequential organ failure assessment score (SOFA), quick sequential organ failure assessment score (qSOFA), and hematological SOFA (SOFAhem) scores on admission. All cases having SOFA score 10 and above and qSOFA score 2 and above died. In multivariate analysis, qSOFA score was found to be statistically significant in predicting mortality in regard to ICU admission (p = 0.004). CONCLUSION: Mortality of febrile neutropenic patients admitted to ICU is high. It would be appropriate to determine the extent of organ dysfunction instead of underlying disease, for making the decision of ICU admission. It should be noticed that the risk mortality is high for the FN cases with SOFA score 10 or above, qSOFA score 2 or above, and in need of mechanical ventilation and positive inotropic support; hence, early intervention is recommended. In our study, the most significant parameter in predicting ICU mortality was found to be qSOFA.

Is the platelet-to-lymphocyte ratio a new prognostic marker in multiple myeloma?

BACKGROUND: Recent reports showed neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. MATERIALS AND METHODS: We retrospectively examined the PLR, NLR, and MLR in a cohort of 186 newly diagnosed multiple myeloma (MM) patients. This study investigated the prognostic relevance of NLR, PLR, and MLR in MM patients. NLR, PLR, and MLR were calculated from whole blood counts before therapy. The Kaplan-Meier curves and multivariate Cox models were used for the evaluation of survival. RESULTS: Applying cutoff of 1.9 (NLR), 120.00 (PLR), and 0.27 (MLR), decreased PLR showed a negative impact on the outcome. Decreased PLR is an independent predictor for PFS and OS. There were no significant differences in median survival between the high and low NLR (P = 0.80) and MLR (P = 0.87) groups. CONCLUSIONS: In this study, thrombocytopenia and low PLR are associated with poor survival in MM patients does this P value apply to thrombocytopenia or low PLR and may serve as the cost-effective prognostic biomarker.

A Comparison of Fresenius Com.Tec Cell and Spectra Optia Cell Separators for Autologous and Allogeneic Stem Cell Collections: Single Center Experience.

Peripheral blood is the prefered source for hematopoietic stem cells for hematopoietic stem cell transplantation. The efficiency of peripheral blood stem cell (PBSC) collection can vary among devices. In this study we aimed to compare feasibility and effectivity of apheresis procedures of the different systems. Two apheresis systems [Com.Tec (Fresenius Healthcare) and Spectra Optia (Caridian BCT)] were used in our center for the collection of PBSCs for autologous and allogeneic transplantation. We retrospectively analysed 190 apheresis procedures performed in healthy donors and patients between June 2012 and November 2014 in Department of Hematology, Dokuz Eylul University. PBSCS were collected by Fresenius cell separator (64 procedure) or Spectra Optia cell separator (126 procedure). Mobilization treatments were G-CSF (26.8%), cyclophosphamide plus G-CSF (48.4%), prelixafor plus G-CSF (14.7%), ESHAP (10%) and others. Patient and donor characteristics (age, weight, volume processed, disease, mobilization regimes) were similar in Fresenius and Spectra Optia apheresis groups. Altough both collected PBSCs efficiently, the amount of CD34+ cell in product collected by Spectra Optia device was significantly higher (p < 0.05) and product volume was lower than Fresenius Com.Tec significantly (p < 0.05). "CD34+ collection efficiency" with Spectra Optia was significantly higher than Fresenius Com.Tec (CE2: 87%, 70%, p = 0.033) regarding all procedures. High collection efficiency and low product volume may be a significant characteristic of Spectra Optia device (mean 187 mL, product CD34+ cell: 1576 µL).

Isolated thrombosis of right spermatic vein with underlying Factor V Leiden mutation.

Spermatic vein thrombosis is a very uncommon clinical entity. Most cases involve the left side. Herein, we present an unusual case of a young man who presented with spermatic vein thrombosis on the right side with an underlying Factor V Leiden mutation. To our knowledge, it is the first case in the literature.

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 old 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.

Ex vivo evaluation of the effect of regulatory T cells on the anti-tumor activity of bortezomib in multiple myeloma.

Multiple myeloma (MM) is a hematologic cancer characterized by malignant proliferation of plasma cells and their precursors. Immunosuppressive CD4+CD25+Foxp3+ regulatory T (Treg) cells are increased in the peripheral blood of patients with MM. On the basis of this finding, we sought to evaluate the ex vivo effect of CD4+CD25+Foxp3+ Treg cells on the anti-tumor effect of the proteosome inhibitor bortezomib on MM cells. We collected peripheral blood and bone marrow aspiration samples from 20 patients with newly diagnosed MM and isolated CD4+CD25+Foxp3+ Treg cells from peripheral blood mononuclear cells. The bone marrow mononuclear cells were cultivated in RPMI at 37°C and 5% CO2 for 72 hours. The LD50 doses of bortezomib, isolated Treg cells, and their combination were added. After 24 hours, the viability of CD138+ myeloma cells was evaluated by WST-1. We compared the anti-tumor effect of bortezomib alone and in combination with Treg expansion and statistically analyzed the measured differences with respect to the clinical parameters of the patients. Treg cells had varied effects on bortezomib, increasing, decreasing, or not changing its anti-tumor effect. The increased in vitro anti-tumor effect of bortezomib after Treg cell expansion was correlated in patients who did not develop bortezomib resistance in vivo (p = 0.022). These patients with in vivo non-bortezomib-resistant MM also responded to Treg expansion with decreased cell viability (p = 0.024). Our data indicate that the ex vivo expansion of Treg cells increased the cytotoxic effect of bortezomib in clinically sensitive cases.

IPSET-Thrombosis Better Identifies Thrombosis-Free Survival: A Turkish Cohort.

INTRODUCTION: Essential thrombocythemia (ET) is the most common of the myeloproliferative neoplasms. For better predicting the occurrence of thrombotic events, an International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) was recently developed. We aimed to investigate the validity of IPSET-Thrombosis in a Turkish patient cohort and to compare the efficacy of IPSET-Thrombosis and conventional risk scoring systems in predicting thrombosis-free survival. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and risk factors for thrombosis in 112 Turkish patients. Median thrombosis-free survival and Harrell C concordance indexes were calculated for both conventional and IPSET-Thrombosis. RESULTS: Median age of 112 patients included in the study was 61 (range, 27-90) years at the time of diagnosis. When patients were stratified according to the conventional risk stratification system, 43.8% of patients were in the low-risk group and 56.2% in the high-risk group. A total of 22.4% of low-risk and 42.9% of high-risk patients had at least one thromboembolic event. When patients were stratified according to the IPSET-Thrombosis, 33% were in the low-risk group, 26.8% in the intermediate-risk group, and 40.2% in the high-risk group. Considering IPSET-Thrombosis risk groups, 5.4% of low-risk, 26.7% of intermediate-risk, and 66.2% of high-risk patients had at least one thromboembolic event. Regarding IPSET-Thrombosis risk groups, 10-year thrombosis-free survival was 86.8% for low-risk, 39.4% for intermediate-risk, and 32.9% for high-risk groups (P < .001). Harrell C concordance indexes of conventional and IPSET-Thrombosis were 0.60 and 0.77, respectively. CONCLUSION: By validating the reproducibility of IPSET-Thrombosis in Turkish ET patients, we found that IPSET-Thrombosis identifies thrombosis-free survival better than the conventional risk stratification system.

Hypoalbuminemia is a surrogate biomarker of poor prognosis in myelodysplastic syndrome even when adjusting for comorbidities.

The serum albumin (SA) level has been reported to be an independent prognostic biomarker that may serve as a surrogate representative of disease biology in patients diagnosed with myelodysplastic syndrome (MDS). However, its prognostic ability has not been tested in a model adjusting for comorbidities. We analyzed 200 patients who were diagnosed as having de novo MDS. Median overall survival (OS) of all patients was 25 months and median leukemia-free survival (LFS) was 24 months. Median OS according to the SA level groups of ≤ 3.5, 3.6-4.0 and > 4.0 mg/dL were 24, 39 and 77 months, respectively. SA level remained an independent predictor of both LFS and OS even when adjusting for the hematopoietic cell transplant comorbidity index (HCT-CI) and the International Prognostic Scoring System (IPSS) or World Health Organization classification-based Prognostic Scoring System (WPSS). Our findings indicate that SA level at the time of diagnosis is a significant and independent predictor of LFS and OS even when adjusting for commonly used prognostic systems and comorbidities.

Renal and neurological response with eculizumab in a patient with transplant associated thrombotic microangiopathy after allogeneic hematopoietic progenitor cell transplantation.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a challenge after allogeneic hematopoietic progenitor cell transplantation, considering the diagnostic uncertainties and lack of established treatment. We report a 43-year-old male patient who was diagnosed as TA-TMA after allogeneic progenitor cell transplantation for a progressive ALK negative anaplastic large cell lymphoma and responded to eculizumab with dramatically improving neurological status and renal function. Rapid neurological and renal recovery achieved after eculizumab could support a possible relationship between complement activation and TA-TMA. Eculizumab should be a reasonable treatment approach in patients with TA-TMA after allogeneic hematopoietic progenitor cell transplantation.

Nilotinib Does Not Alter the Secretory Functions of Carotid Artery Endothelial Cells in a Prothrombotic or Antithrombotic Fashion.

BACKGROUND: There have been concerns about the possible prothrombotic effects of nilotinib, especially in patients having cardiovascular risk factors. The potential mechanism behind the increased risk of thromboembolic events is still not clear. OBJECTIVES: In this study, we aimed to evaluate possible harmful effects of nilotinib on endothelial cells. To this aim, we examined proliferative capacity and secretory functions of healthy human carotid artery endothelial cells (HCtAECs) in response to nilotinib. METHODS: 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation method was used to determine antiproliferative effects of nilotinib on HCtAECs. The HCtAECs were incubated with 5, 10, and 100 nmol/L doses of nilotinib for 72 hours. Then, in order to assess the endothelial function, levels of nitric oxide (NO), von Willebrand factor (vWF), tissue plasminogen activator, plasminogen activator inhibitor 1 (PAI-1), and endothelin 1 (ET-1) were evaluated using enzyme-linked immunosorbent assay from tissue culture supernatants. RESULTS: There were slight but statistically significant decreases in cell proliferation in response to nilotinib. Nilotinib increased the secretion of t-PA, PAI-1, and vWF in a dose-dependent manner when compared with the untreated control group. The ET-1 secretion was lower in 5 nmol/L and higher in 10 and 100 nmol/L nilotinib-treated cells as compared to untreated cells. Regarding NO secretion, lower levels were observed in 5 and 10 nmol/L, and higher levels were detected in 100 nmol/L nilotinib-treated cells as compared to untreated control group cells. CONCLUSION: Considering the results obtained in our study, nilotinib does not affect the functions of endothelial cells either in a prothrombotic or an antithrombotic fashion, despite a dose-dependent decline in cell viability.

Successful hematopoietic engraftment with gray platelets after allogeneic hematopoietic stem cell transplantation from gray platelet syndrome donor.

Gray platelet syndrome (GPS) is a rare inherited disorder characterized by the absence of α-granules and their constituents. It may be present with thrombocytopenia and bleeding tendency. Platelets have a large and gray appearance under light and electron microscope. A 19-year old female patient with her second relapse acute lymphoblastic leukemia had to be consolidated with allo-hematopoietic stem cell transplantation (HSCT) after achieving remission with induction chemotherapy. The only available and one mismatch compatible donor was her brother, who was previously diagnosed as GPS. Allogeneic HSCT was performed from her brother in spite of GPS, and successful neutrophil and platelet engraftment achieved at the 12th and 42nd day of reinfusion, consecutively. The engrafted and circulating thrombocytes were large and gray and had little or no α-granules under electron microscope. The patient was well with no major bleeding event and increased need for thrombocyte replacement until developing bronchiolitis obliterans organizing pneumonia and respiratory distress syndrome. Thereafter death occurred. This is the first case of successful thrombocyte engraftment with documented gray thrombocyte megakaryopoiesis after allogeneic HSCT from a GPS donor. The only noteworthy issue was the slight prolongation of engraftment.

Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report.

INTRODUCTION: Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. CASE PRESENTATION: We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. CONCLUSION: Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.