Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience.

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.

Ruxolitinib for the treatment of inadequately controlled polycythemia vera without splenomegaly: 80-week follow-up from the RESPONSE-2 trial.

RESPONSE-2 is a phase 3 study comparing the efficacy and safety of ruxolitinib with the best available therapy (BAT) in hydroxyurea-resistant/hydroxyurea-intolerant polycythemia vera (PV) patients without palpable splenomegaly. This analysis evaluated the durability of the efficacy and safety of ruxolitinib after patients completed the visit at week 80 or discontinued the study. Endpoints included proportion of patients achieving hematocrit control (< 45%), proportion of patients achieving complete hematologic remission (CHR) at week 28, and the durability of hematocrit control and CHR. At the time of analysis, 93% (69/74) of patients randomized to ruxolitinib were receiving ruxolitinib; while in the BAT arm, 77% (58/75) of patients crossed over to ruxolitinib after week 28. No patient remained on BAT by week 80. Among patients who achieved a hematocrit response at week 28, the probability of maintaining response up to week 80 was 78% in the ruxolitinib arm. At week 80, durable CHR was achieved in 18 patients (24%) in the ruxolitinib arm versus 2 patients (3%) in the BAT arm. The safety profile of ruxolitinib was consistent with previous reports. These data support that ruxolitinib treatment should be considered also as a standard of care for hydroxyurea-resistant/hydroxyurea-intolerant PV patients without palpable splenomegaly.

Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study.

BACKGROUND: In the pivotal RESPONSE study, ruxolitinib, a Janus kinase (JAK)1 and JAK2 inhibitor, was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea. In this study, we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy. METHODS: RESPONSE-2 is a randomised, open-label, phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia, Australia, Europe, and North America. Eligible patients (aged ≥18 years) with polycythaemia vera, no palpable splenomegaly, and hydroxyurea resistance or intolerance were stratified by their hydroxyurea therapy status (resistance vs intolerance) and randomly assigned (1:1) by an interactive response technology provider using a validated system to receive either oral ruxolitinib 10 mg twice daily or investigator-selected best available therapy (hydroxyurea [at the maximum tolerated dose], interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment). Investigators and patients were not masked to treatment assignment; however, the study sponsor was masked to treatment assignment until database lock. The primary endpoint was the proportion of patients achieving haematocrit control at week 28. Analyses were done according to an intention-to-treat principle, including data from all patients randomly assigned to treatment. This study is registered with ClinicalTrials.gov (NCT02038036) and is ongoing but not recruiting patients. FINDINGS: Between March 25, 2014, and Feb 11, 2015, of 173 patients assessed for eligibility, 74 patients were randomly assigned to receive ruxolitinib and 75 to receive best available therapy. At randomisation, best available therapy included hydroxyurea (37 [49%] of 75 in the best available therapy group), interferon or pegylated interferon (ten [13%] of 75), pipobroman (five [7%] of 75), lenalidomide (one [1%] of 75), no treatment (21 [28%] of 75), and other (one [1%] of 75). Haematocrit control was achieved in 46 (62%) of 74 ruxolitinib-treated patients versus 14 (19%) of 75 patients who received best available therapy (odds ratio 7·28 [95% CI 3·43-15·45]; p<0·0001). The most frequent haematological adverse events of any grade were anaemia (ten [14%] of 74 in the ruxolitinib group vs two [3%] of 75 in the best available therapy group) and thrombocytopenia (two [3%] vs six [8%]). No cases of grade 3-4 anaemia or thrombocytopenia occurred with ruxolitinib; one patient (1%) reported grade 3-4 anaemia and three patients (4%) reported grade 3-4 thrombocytopenia in the group receiving best available therapy. Frequent grade 3-4 non-haematological adverse events were hypertension (five [7%] of 74 vs three [4%] of 75) and pruritus (0 of 74 vs two [3%] of 75). Serious adverse events occurring in more than 2% of patients in either group, irrespective of cause, included thrombocytopenia (none in the ruxolitinib group vs two [3%] of 75 in the best available therapy group) and angina pectoris (two [3%] of 74 in the ruxolitinib group vs none in the best available therapy group). Two deaths occurred, both in the best available therapy group. INTERPRETATION: RESPONSE-2 met its primary endpoint. The findings of this study indicate that ruxolitinib could be considered a standard of care for second-line therapy in this post-hydroxyurea patient population. FUNDING: Novartis.

Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors.

OBJECTIVES AND AIM: In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). PATIENTS AND METHODS: The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. RESULTS: A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). CONCLUSION: Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT.

Factors affecting survival in acute leukemia with donor lymphocyte infusion in the first relapse after allogeneic stem cell transplantation.

PURPOSE: Relapse of leukemia relapsing after allogeneic (allo) stem cell transplantation (SCT) remains an important problem. Cytoreductive chemotherapy followed by donor leukocyte infusion (DLI) is one of the treatment modalities in relapsed patients. The current study evaluated the factors affecting overall survival (OS) in allo-SCT patients who received DLI after the first relapse. METHODS: In this retrospective study 54 patients (26 with acute myeloid leukemia [AML] and 28 with acute lymphoblastic leukemia [ALL]) in their first relapse after allo-SCT who received fludarabine-based chemotherapy followed by DLI were evaluated. RESULTS: The relative risk for mortality was significantly higher in patients with acute leukemia (AL) within the high-risk group who went through transplantation (risk ratio: 4.866; 95% CI: 2.029-11.670;p<0.001) and in transplants performed in the remission phases following the first complete remission (risk ratio: 2.371; 95% CI: 1.154 - 4.872; p=0.019). Additionally, the relative mortality risk of transplantation in patients with acute leukemia (AL) with a number of DLIs applied (risk ratio: 0.456; 95% CI: 0.29 - 0.717; p=0.001) nd non-myeloablative regimen (risk ratio: 0.229; 95% CI: 0.053-0.992; p=0.049) was significantly lower. CONCLUSION: Efforts to enhance the number of DLIs, thus the number of infused cells, may result in better OS in cases with AL with relapse.

Multicenter retrospective analysis regarding the clinical manifestations and treatment results in patients with hairy cell leukemia: twenty-four year Turkish experience in cladribine therapy.

In this multicenter retrospective analysis, we aimed to present clinical, laboratory and treatment results of 94 patients with Hairy cell leukemia diagnosed in 13 centers between 1990 and 2014. Sixty-six of the patients were males and 28 were females, with a median age of 55. Splenomegaly was present in 93.5% of cases at diagnosis. The laboratory findings that came into prominence were pancytopenia with grade 3 bone marrow fibrosis. Most of the patients with an indication for treatment were treated with cladribine as first-line treatment. Total and complete response of cladribine was 97.3% and 80.7%. The relapse rate after cladribine was 16.6%, and treatment related mortality was 2.5%. Most preferred therapy (95%) was again cladribine at second-line, and third line with CR rate of 68.4% and 66.6%, respectively. The 28-month median OS was 91.7% in all patients and 25-month median OS 96% for patients who were given cladribine as first-line therapy. In conclusion, the first multicenter retrospective Turkish study where patients with HCL were followed up for a long period has revealed demographic characteristics of patients with HCL, and confirmed that cladribine treatment might be safe and effective in a relatively large series of the Turkish study population.

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.

Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

A rare but severe complication of filgrastim in a healthy donor: splenic rupture.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is widely administered to donors who provide peripheral blood stem cells (PBSCs) for individuals who undergo hematopoietic stem cell transplants. G-CSF administration is associated with a small but definite risks of serious adverse events like splenic rupture. CASE STUDY: In this case, we report a 40 year old women, a healthy donor for her sister who has aplastic anemia, who had sharp left upper abdominal pain on the forth mobilization day. The diagnosis at CT scan was splenic rupture; irregular intrasplenic low-attenuation areas consistent with ruptured spleen and perisplenic high density fluid. Her bidimensional spleen size was 16×6 cm. RESULTS: She was followed conservatively. One month later the CT scan signs of rupture disappeared. CONCLUSION: We must pay attention to this rare but serious adverse event during filgrastim use.

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 donor's 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 effect of volume replacement during therapeutic leukapheresis on white blood cell reduction in patients with extreme leukocytosis.

BACKGROUND: Extreme leukocytosis, generally defined as a white blood cell (WBC) count of more than 100 × 10(9) /L consisting largely of blast cells, especially when accompanied by clinical signs and symptoms of leukostasis or hyperviscosity, often predicts a poor clinical outcome in patients with acute leukemia. In this study, we aimed to investigate the effect of volume replacement (VR) during therapeutic leukapheresis (TA) procedure on early mortality rate and WBC reduction. STUDY DESIGN AND METHODS: We retrospectively analyzed 29 patients who underwent TA from 2007 to 2011. Fifteen of the patients underwent TA procedure with VR and 14 of the patients underwent TA procedure without VR. RESULTS: WBC reduction was significantly higher in patients who underwent TA with VR (p < 0.001). Early mortality rate was significantly lower in leukemia patients who underwent TA with VR than in patients who underwent TA without VR (p < 0.01); early mortality rates were 6.7% for 7-day and 13.8% for 100-day survivals. The mortality rates in the TA without VR group, however, were 42.9 and 71.4% for 7- and 100-day survivals, respectively. CONCLUSION: Decreased early mortality rate in TA with VR group may be associated with prompt reduction of WBCs achieved with TA with VR and may also be associated with removal of the cytokines related to leukostasis. TA with VR would give more time for induction chemotherapy and increased overall survival rate.

The management of iron overload in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients: where do we stand?

Iron overload (IO), primarily related to multiple red blood cell transfusions, is a relatively common complication in hematopoietic stem cell transplant (HSCT) recipients. Elevated pretransplant ferritin levels have been reported to increase the risk of non-relapse mortality following HSCT and might influence the risk of acute and chronic graft versus host disease. IO has been shown to be an important cause of mortality and morbidity in patients who have undergone alloHSCT (Armand et al., Blood 109:4586-4588, 2007; Kim et al., Acta Haematol 120:182-189, 2008; Kataoka et al., Biol Blood Marrow Transplant 15:195-204, 2009). We know that excessive iron accumulation results in tissue damage and organ failure, mainly as a result of the generation of free radicals that cause oxidative damage and organ dysfunction (e.g., hepatotoxicity, cardiotoxicity, and endocrine dysfunction) (Altes et al., Bone Marrow Transplantation 29: 987-989, 2002; Papanikolaou et al., Toxicol Appl Pharmac 202:199-211, 2005). In the last decade, efforts have been directed toward identifying alternative treatment for IO in alloHSCT recipients to maintain improved transplant outcomes.

The effect of diabetes mellitus and end-stage renal disease on the number of CD34+ cells in the blood.

The aim of this study was to investigate the effect of end-stage renal disease (ESRD) and diabetes mellitus (DM) on the number of stem cells in the peripheral blood. Sixty-two patients diagnosed with ESRD who had not received dialysis previously, 25 patients with a diagnosis of DM without nephropathy, and 21 healthy volunteers were included in the study. The group diagnosed with ESRD was divided into two groups. The first group (DM-CRD) consisted of 28 patients with DM who had developed chronic renal disease (CRD). The second group (NON-DM-CRD) consisted of 34 patients without DM who had CRD by etiology. The routine complete blood count, renal function, and number of CD34+ cells were determined for all of those involved in the study. The microalbumin/creatinine levels were measured, and glomerular filtration rates were calculated in all patients. The number of CD34+ cells was found to be significantly lower in the DM control group and DM-CRD group compared with the healthy group. No statistically significant difference was found between the NON-DM-CRD and the healthy control group. There was a moderate negative correlation between the ratio of microalbumin/creatinine and the number of CD34+ cells. A significant reduction in the number of CD34+ cells was shown in subjects with DM and ESRD caused by diabetic nephropathy.

Treatment with plasma exchange may serve benefical effect in patients with severe hyperbilirubinemia: a single center experience.

Hyperbilirubinemia is a common clinical manifestation, and may be life threatening. Many diseases result in hyperbilirubinemias, some are refractory, and cannot be cured by medication or surgery. Plasma exchange (PE) for hyperbilirubinemia is not a pathogenesis oriented therapy but strives for the opportunity to cure. In the present study, we aimed to present the outcomes of treatment of hyperbilirubinemia with PE in patients with various disorders. Eleven patients who underwent PE due to hyperbilirubinemia between 2006 and 2012 in Apheresis Unit of Erciyes University, were retrospectively reviewed. After PE, we observed a marked decline in total and direct bilirubin levels. The decline in the biochemical values were statically significant (p<0.003). Both total and direct bilirubin levels remained above the normal limits in one of 11 patients. PE should be considered as an effective and safe option in cases with hyperbilirubinemia, and this procedure can improve survival in patients with sufficient residual capacity of liver regeneration.

The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload.

INTRODUCTION: Iron overload (IO) has been shown to be an important cause of mortality and morbidity in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treatment (deferasirox) on survival in alloHSCT recipients in the posttransplant period. MATERIALS AND METHODS: A total of 80 alloHSCT recipients with IO were analyzed, retrospectively. Pretransplant and posttransplant data were obtained from the patients' files. Patients were divided into two groups. Group 1; patients who did not receive any chelator treatment due to side effects or compliance problems. These patients were treated by phlebotomy. Group 2 consisted of patients who received deferasirox treatment. RESULTS: The median treatment duration with deferasirox was 122 days (min-max:91-225). The iron chelating treatment significantly reduced serum ferritin levels administered at a dosage of 20-30 mg/kg/day (p<0.001). The median OS in Group 1 was found 16.0 (min-max:1.0-63.0) months and 25.0 (min-max:3.0-72.0) months in Group 2. In univariate and multivariate analysis, patients in Group 1 showed poorer OS compared to those in Group 2 with an increase in risk of death (HR:3.22, min-max:1.67-6.23, p=0.001 and HR:3.51,, min-max:1.75-6.99, p<0.001; respectively). The median DFS in Group 1 was found 11.0 (min-max:3.0-24.0) months and 22.0 (min-max:8.0-43.0) months in Group 2. The difference was found statistically significant (p=0.023). The other factors that we found significant difference in multivariate analysis between groups were; presence of acute GVHD (patients with aGVHD had increased risk of death compared to patients without aGVHD (HR:2.49, min-max: 1.32-4.69, p=0.005), chronic GVHD (HR:2.57, min-max:1.23-5.41, p=0.013), median interval to tx (HR: 2.23, min-max:1.17-4.26, p=0.015) and HLA match (HR:3.01, min-max:1.35-6.73, p=0.007) CONCLUSION: Oral deferasirox (Exjade) treatment may improve survival in patients with iron overload who underwent alloHSCT.

Changes in CD34+ cell count in peripheral blood after whole blood donation.

AIM: We aimed to investigate the change in the number of stem cells and white cells in the early period following blood donation. PATIENTS AND METHOD: 22 male (71%) and 9 female (29%), 31 volunteers in total were included in the study. 450 ml of whole blood were collected from each of the volunteers for the donation. Complete blood counts were performed on the volunteers before and at 6 and 24h after the donation and CD34+ cell counts per ml of peripheral blood were measured by flow cytometry technique. RESULTS: There was a statistically significant increase in the number of CD34+ cells in the peripheral blood at 6h following blood donation (p<0.001). At 24h, however, there was a statistically significant decrease in the number of CD34+ cells, compared to 6h (p<0.001). There was a statistically significant increase in the number of leukocytes in the peripheral blood at 6h following blood donation (p<0.001). At 24h, there was a decrease in the number of leukocytes, which was statistically significant compared to 6h (p<0.001). When the difference in CD34+ cell and leukocytes counts before blood donation and at 24h after blood donation were compared, the results were not statistically significant. CONCLUSION: As the result of this study, a transient increase in the number of CD34+ cells in the peripheral blood after blood donation was demonstrated, with a decline in CD34+ cell counts back to levels prior to donation at 24h.

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.

The comparison of Filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) as a first line peripheral blood stem cell mobilization strategy in autologous hematopoieitic stem cell transplantation: a single center experience from Turkey.

OBJECTIVES AND AIM: Patients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT). MATERIALS AND METHODS: We retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients' files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34(+) cell count at the end of mobilization procedure. RESULTS: A total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3×10(6) CD34(+)/kg was 2 in Neupogen® (min-max: 1-4) and Granocyte® (min-max: 1-3) groups and 1 (min-max: 1-2) in Leucostim® group. The median doses of G-CSF agents (µg/kg/day) in PBSC collection procedure were; 10.00 (min-max: 7.00-12.00) in the Neupogen® group, 8.00 (min-max: 7.25-9.00) in the Leucostim® group and 8.50 (6.00-9.50) in the Granocyte® group. There was no statistical significance among groups (p=0.067). The number of total collected PB CD34(+) cells (×10(6)/kg) was 7.64 (min-max: 4.09-13.86) in the Neupogen® group, 13.43 (min-max: 8.15-23.38) in the Leucostim® group and 5.45 (min-max: 4.28-9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34(+) cells compared to patients in the Granocyte® group (p=0.013). CONCLUSION: Leucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT.

The management of hyperleukocytosis in an adult patient with acute lymphoblastic leukemia and ataxia-telangiectasia.

Ataxia-telangiectasia (AT) is a hereditary disorder characterized by progressive neurological dysfunction, oculocutaneous telangiectasia, immunodeficiency, cancer susceptibility, and radiation sensitivity. Pediatric patients may develop acute lymphoblastic leukemia (ALL). However development of ALL in an adult patient with AT is a rare occurrence. Here we report such a patient who presented with hyperleukocytosis and were treated with leukapheresis. A 25years old male patient, who were diagnosed with AT and mental retardation, was admitted to the emergency department due to fatigue, nausea and headache. On admission he had a moderate general condition and was fully cooperated. His white blood cell (WBC) count were 466×10(9)/l. Blastic cells were observed in peripheral blood smear. Flow cytometry (FC) of peripheral blood showed T-ALL. Two sessions of large volume leukapheresis was performed. Symptoms due to hyperleukocytosis markedly improved after leukapheresis. Patients with AT should be closely monitored due to risk of malignancy. Leukapheresis may improve the prognosis of high risk ALL patients presenting with hyperleukocytosis.

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.