Muzaffer Keklik

Therapeutic plasma exchange in patients with thrombotic thrombocytopenic purpura: A retrospective multicenter study

UNLABELLED Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. TTP requires a rapid diagnosis and an adapted management in emergency. Daily sessions of therapeutic plasma exchange (TPE) remain the basis of management of TTP. Also, TTP is a rare disease that is fatal if it is not treated. TPE has resulted in excellent remission and survival rates in TTP patients. AIM We aimed to present our experience in 163 patients with TTP treated with TPE during the past 5years from 10 centers of Turkey. PATIENTS AND METHODS One hundered and sixty-three patients with TTP treated with TPE during the past 5years from 10 centers of Turkey were retrospectively evaluated. TPE was carried out 1-1.5times plasma volume. Fresh frozen plasma (FFP) was used as the replacement fluid. TPE was performed daily until normalization of serum lactate dehydrogenase (LDH) and recovery of the platelet count to >150×10(9)/dL. TPE was then slowly tapered. Clinical data, the number of TPE, other given therapy modalities, treatment outcomes, and TPE complications were recorded. RESULTS Fifty-eight percent (95/163) of the patients were females. The median age of the patients was 42years (range; 16-82). The median age of male patients was significantly higher than female (53 vs. 34years; p<0.001). All patients had thrombocytopenia and microangiopathic hemolytic anemia. At the same time, 82.8% (135/163) of patients had neurological abnormalities, 78.5% (128/163) of patients had renal dysfunction, and 89% (145/163) of patients had fever. Also, 10.4% (17/163) of patients had three of the five criteria, 10.4% (17/163) of patients had four of the five criteria, and 6.1% (10/163) of patients had all of the five criteria. Primary TTP comprised of 85.9% (140/163) of the patients and secondary TTP comprised of 14.1% (23/163) of the patients. Malignancy was the most common cause in secondary TTP. The median number of TPE was 13 (range; 1-80). The number of TPE was significantly higher in complete response (CR) patients (median 15.0 vs. 3.5; p<0.001). CR was achieved in 85.3% (139/163) of the patients. Similar results were achieved with TPE in both primary and secondary TTP (85% vs. 87%, respectively; p=0.806). There was no advantage of TPE+prednisolone compared to TPE alone in terms of CR rates (82.1% vs. 76.7%; p=0.746). CR was not achieved in 14.7% (24/163) of the patients and these patients died of TTP related causes. There were no statistical differences in terms of mortality rate between patients with secondary and primary TTP [15% (21/140) vs. 13% (3/23); p=0.806]. But, we obtained significant statistical differences in terms of mortality rate between patients on TPE alone and TPE+prednisolone [14% (12/86) vs. 3% (2/67), p<0.001]. CONCLUSIONS TPE is an effective treatment for TTP and is associated with high CR rate in both primary and secondary TTP. Thrombocytopenia together with microangiopathic hemolytic anemia is mandatory for the diagnosis of TTP and if these two criteria met in a patient, TPE should be performed immediately.

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (p<0.001) and free triiodotyhronin (FT3) (p<0.004) levels. There was statistically significant increase in the mean values of TSH levels after TPE (p<0.001). Clinical improvement was achieved in hyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy.

Pretransplant iron overload may be associated with increased risk of invasive fungal pneumonia (IFP) in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT)

Invasive fungal pneumonia (IFP) has become increasingly common in patients that previously underwent alloHSCT. The aim of this study was to determine the role of hyperferritinemia, via iron overload in invasive fungal pneumonia in patients that underwent alloHSCT. Medical records of 73 patients with pneumonia that underwent alloHSCT were studied retrospectively, whereby a pre-transplantation serum ferritin level measured up to 100 days prior to transplantation of patients with invasive fungal pneumonia (IFP) and non-fungal pneumonia (non-IFP) was compared. Patient records revealed 35 and 38 cases of IFP and non-IFP, respectively. In risk evaluation for IFP, age, gender, HLA status, conditioning regimen, smoking history, and underlying disease were not significantly different among groups (p>0.05). However, performance status (Karnofsky) was significantly lower in patients with IFP (p<0.05). The median ferritin levels were 1,705 ng/ml (41-7198) in the IFP group and 845 ng/ml (18-7099) in non-IFP group and the difference was found statistically significant (p=0.001). Elevated pretransplant serum ferritin level is associated with IFP in patients that underwent alloHSCT, in particular when values exceed 1550 ng/ml.

Comparison of plateletpheresis on the Fenwal Amicus, Fresenius COM.TEC, and Trima Accel Cell separators

Blood component donations by apheresis have become more common in modern blood transfusion practices. We compared three apheresis instruments (Fenwal Amicus, Fresenius COM.TEC, and Trima Accel) with regard to platelet (PLT) yield, collection efficiency (CE), and collection rate (CR). The single‐needle or double‐needle plateletpheresis procedures of the three instruments were compared in a retrospective, randomized study in 270 donors. The blood volume processed was higher in the COM.TEC compared with the Amicus and Trima. Also there was a significantly higher median volume of ACD used in collections on the COM.TEC compared with the Amicus and Trima. The PLT yield was significantly lower with the COM.TEC compared with the Amicus and Trima. Additionally, the CE was significantly lower with the COM.TEC compared with the Amicus and Trima. There was no significant difference in median separation time and CR between the three groups. When procedures were compared regarding CE by using Amicus device, it was significantly higher in single‐needle than double‐needle plateletpheresis. When double‐needle Amicus system was compared with double‐needle COM.TEC system, CE and PLT yield were significantly higher with Amicus system. When single‐needle Amicus system was compared with single‐needle Trima system, CE and PLT yield were significantly higher with Trima system. All instruments collected PLTs efficiently. However, the CE was lower with the COM.TEC compared with the Amicus and Trima. Also, we found Amicus single‐needle system collected PLTs more efficiently compared with the double‐needle system. CE and PLT yields were significantly higher with the single‐needle Trima instrument compared with the single‐needle Amicus device. J. Clin. Apheresis 30:171–175, 2015.

Contribution of involved-field radiotherapy to survival in patients with relapsed or refractory Hodgkin lymphoma undergoing autologous stem cell transplantation.

Objectives:To assess the outcomes of overall survival and posttransplantation survival in patients with Hodgkin lymphoma (HL) undergoing autologous stem cell transplantation (ASCT) because of the development of relapse or resistance after chemotherapy (CT) or CT plus radiotherapy (combined modality treatment, CMT). Methods:Forty-five patients undergoing ASCT because of the development of relapse or resistance after CT or CMT for HL were enrolled in the study. Radiotherapy was given as involved-field radiotherapy. Patients were treated with CT alone (n=25) or CMT (n=20). These 2 groups were further divided into 2 subgroups: the patients with early-stage (I to II) and advanced-stage (III to IV) HL. Results:Median patients age was 29 years (range, 16 to 60 y) and the median follow-up was 60 months (range, 12 to 172 mo). In the patients with advanced-stage HL, there was no statistically significant difference in overall survival between irradiated and nonirradiated patients (n=18, irradiated n=4 and nonirradiated n=14). However, in the patients with early-stage disease, there was a significant difference in 5- and 10-year overall survival between the irradiated and nonirradiated groups (81% vs. 48% and 66% vs. 24%, respectively, P=0.045; n=26, irradiated n=16 and nonirradiated n=10). In the univariate analysis, irradiated group and involvement of 1 to 2 nodal regions were found to be significant for overall survival, whereas irradiated group, early stage, and involvement of 1 to 2 nodal regions were found to be significant for posttransplantation survival. However, only irradiated group was found to be significant for posttransplantation survival in multivariate analysis (P<0.05). Conclusions:Addition of involved-field radiotherapy to CT in patients undergoing ASCT after relapse or recurrence failed to provide survival benefit in patients with advanced HL, while a survival benefit was observed in patients with early-stage HL. Radiotherapy should be considered as part of CMT in the patients with early-stage HL, which should not be neglected.

Performance of Galactomannan Antigen, Beta-d-Glucan, and Aspergillus-Lateral-Flow Device for the Diagnosis of Invasive Aspergillosis

Aspergillus lateral-flow device (LFD) was recently introduced as a practical tool for the diagnosis of invasive aspergillosis (IA). We investigated the performance of Aspergillus-LFD as a point-of-care test for the diagnosis of IA. Serum samples were collected twice weekly from patients who received intensive chemotherapy for acute leukemia, or recepients of allogeneic stem cell transplantation. Aspergillus galactomannan (GM) antigen, 1,3-beta-d-glucan and Aspergillus-LFD tests were carried out according to manufacturers’ recommendations. GM testing was repeated with a modified procedure which was proven to increase the sensitivity. Aspergillus-LFD was performed without applying any pretreatment procedure to allow the kit to fit as a point-of-care test. Fungal infections were categorized according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. A total of 75 neutropenia episodes in 64 patients were prospectively followed between February 2012 and January 2013. Probable IA was diagnosed in 11 patients, probable pulmonary fungal disease was diagnosed in one patient, and rhinocerebral aspergillosis was diagnosed in one patient. Fungemia was detected in two patients. Aspergillus-LFD was positive in serum of a patient with probable IA and in the bronchoalveolar lavage fluid of an other patient with probable IA. Aspergillus-LFD was false positive in serum of two patients. Although there was no radiological finding of IA or documented fungemia, fever resolved after empirical caspofungin therapy in one of these patients. The sensitivity of Aspergillus-LFD as a point-of-care test without any pretreatment of serum sample is low.

Comparison of double dose plateletpheresis on the Fenwal Amicus, Fresenius COM.TEC and Trima Accel cell separators

BACKGROUND A variety of apheresis instruments are now available on the market for double dose plateletpheresis. We compared three apheresis devices (Fenwal Amicus, Fresenius COM.TEC and Trima Accel) with regard to processing time, platelet (PLT) yield, collection efficiency (CE) and collection rate (CR). STUDY DESIGN AND METHODS The single-needle or double-needle double plateletpheresis procedures of the three instruments were compared in a retrospective, randomized study in 135 donors. RESULTS In the pre-apheresis setting, 45 double plateletpheresis procedures performed with each instrument revealed no significant differences in donors age, sex, weight, hemoglobin, white blood cell and PLT count between three groups. The blood volume processed to reach a target PLT yield of ≥ 6 × 10(11) was higher in the COM.TEC compared with the Amicus and Trima (4394 vs. 3780 and 3340 ml, respectively; p < 0.001). Also there was a significantly higher median volume of ACD used in collections on the COM.TEC compared with the Amicus and Trima (426 vs. 387 and 329 ml, respectively; p < 0.001). There was a significantly higher median time needed for the procedures on the COM.TEC compared with the Amicus and Trima (66 vs. 62 and 63 min, respectively; p = 0.024). The CE was significantly higher with the Trima compared with the Amicus and COM.TEC (83.57 ± 17.19 vs. 66.71 ± 3.47 and 58.79 ± 5.14%, respectively; p < 0.001). Also, there was a significantly higher product volume on the Trima compared with the Amicus and COM.TEC (395.56 vs. 363.11 and 386.4 ml, respectively; p = 0.008). Additionally, the CR was significantly lower with the COM.TEC compared with the Amicus and Trima (0.092 ± 0.011 vs. 0.099 ± 0.013 and 0.097 ± 0.013 plt × 10(11)/min, respectively; p = 0.039). There was no significant differences in PLT yield between the three groups (p = 0.636). CONCLUSIONS Trima single-needle device collected double dose platelets more efficiently than Amicus and COM.TEC double-needle devices. Blood volume processed, ACD-A volume, and median separation time was significantly higher with the COM.TEC. Also, the CR was significantly lower with the COM.TEC.

The impact of pretransplant hypoalbuminemia on survival in patients with leukemia who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT): a nutritional problem?

OBJECTIVE Serum albumin level is considered to be a marker reflecting the nutritional status in both healthy subjects and patients with malignancies. In this study we sought to investigate the association between pretransplantation serum albumin levels and prognosis among patients with leukemia who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). METHODS We retrospectively analyzed the data of 102 patients who underwent alloHSCT from 2004 to 2010. Pretransplant serum albumin, D-dimer, creatinine, and fibrinogen levels drawn within 10 days before transplantation were obtained from patient files. All parameters were divided into 2 groups: normal levels (group 1) versus abnormal levels (group 2). Our normal range of serum albumin is 3.2-5.2 g/dL; patients with pretransplantation albumin level ≥3.2 g/dL were included in group 1 versus group 2 with <3.2 g/dL. RESULTS The patients included 42 (41.1%) female and 60 (58.9%) male patients. The diagnoses were acute myeloblastic leukemia in 65 (63.7%) and acute lymphoblastic leukemia in 37 (36.3%). The median age was 26.0 years (range, 13-57). Univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL experienced significantly lower overall survival (OS) compared with ≥3.2 g/dL (hazard ratio [HR] 2.32 [range, 1.23-4.54] and HR 2.70 [range 1.38-5.26], respectively; P = .009). The median (range) OS in group 2 was 230.0 (184.0-544.0) days versus 570.5 (249.5-1,101.0) days in group 1 (P = .007). For disease free survival (DFS) evaluation, univariate and multivariate analysis showed that patients with serum albumin levels <3.2 g/dL had significantly lower values compared with patients with serum albumin ≥3.2 g/dL. (HR 2.17 [range 0.98-4.76] and HR 2.85 [range, 1.25-6.66], respectively; P = .046). The median (range) DFS in group 2 was 184.0 (61.0-524.0) days versus 445.0 (199.0-917.5) days in group 1 (P = .045). Among the patient characteristics the presence of infection was a significant independent variable for worse OS (HR 2.12 [range, 0.98-4.36], P = .036). The other parameters-age, sex, donor status, time to transplant interval, conditioning regimens, HLA status, and number of total infused CD34(+) cells-showed no significant effect on OS and DFS (P = .05). CONCLUSIONS Pretransplantation decreased serum albumin levels were associated with poor survival in patients with leukemia who underwent alloHSCT.

Effectiveness of the haemonetics MCS cell separator in the collection of apheresis platelets.

Platelet (PLT) transfusions play an important role in patients with thrombocytopenia or severely impaired platelet function. Platelet concentrates are prepared from whole-blood donations or by plateletpheresis. In recent years, different instruments have been developed to perform plateletpheresis. We evaluated an apheresis instrument, the Haemonetics MCS(®) + with regard to PLT yield, collection efficiency (CE), and collection rate (CR) in a retrospective, randomized study in 526 donors. In this system, we used leukoreduction filters post collection to obtain leukoreduced products. The Haemonetics MCS(®) + cell separator efficiently collected apheresis platelets with median PLT yields of 3.7 × 10(11), mean CE of 66.69 ± 13.73% and mean CR of 0.063 ± 0.013 × 10(11)/min. The median blood volume processed was 3290 (2420-4370) ml, and the median volume of acid citrate dextrose-A (ACD-A) used in collections on the device was 385 (196-517) ml. Also, this device allowed the collection of white blood cell (WBC) reduced plateletpheresis with mean 0.07 ± 0.15 × 10(6) WBC content. No serious donor or recipient reactions occurred.

Pericardial, pleural and peritoneal involvement in a patient with primary gastric mantle cell lymphoma.

Primary gastric mantle cell lymphoma is a rare form of gastointestinal tumour. Although peritoneal carcinomatosis accompanied by malignant ascites is relatively common, mantle cell lymphoma presenting with ascites is rare. Also, effusions involving pericardial and pleural cavities are uncommon during the course of lymphomas. We report the first case in which pericardial, pleural and peritoneal effusion of a primary gastric mantle cell lymphoma.