Summary 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.
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.
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.
Abstract 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 (×106 /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.
Chronic antigenic stimulation is frequently blamed in the pathogenesis of extranodal marginal zone lymphomas including splenic marginal zone lymphoma (SMZL). Chronic hepatitis C is frequently ...observed in SMZL patients in some geographical regions. However, these reports are largely from North America and Europe, and data from other countries are insufficient. In this multicenter study we aimed to identify the clinical characteristics of SMZL patients in Turkey, including viral hepatitis status and treatment details.
Data were gathered from participating centers from different regions of Turkey using IBM SPSS Statistics 23 for Windows. Hepatitis B virus surface antigen (HBsAg), anti-HBs antibody, anti-HB core antigen antibody (anti-HBcAg), HB viral load, anti-hepatitis C virus (HCV) antibody, HCV viral load results were analyzed.
One hundred and four patients were reported. Hepatitis C virus positivity was observed in only one patient. However, hepatitis B virus surface antigen (HBsAg) positivity was observed in 11.2% and HBsAg and/or anti-HB core antigen antibody (anti-HBcAg) positivities were seen in 34.2% of the patients. The median age was 60 years (range=35-87). Median follow-up duration was 21.2 months (range=00.2-212; 23.2 months for surviving patients). Median overall survival was not reached. Estimated 3-year and 10-year survival rates were 84.8% and 68.9%, respectively. Older age, no splenectomy during follow-up, platelet count of <90x10
/μL, lower albumin, higher lactate dehydrogenase, higher β
-microglobulin, and HBsAg positivity were associated with increased risk of death. Only albumin remained significant in multivariable analysis.
These results indicate that hepatitis B virus may be a possible risk factor for SMZL in our population. It may also be an indirect prognostic factor.
Abstract Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years ...such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals’ aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units’ were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5–85) years. Of these patients 58.3% were Guillain–Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1–72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients. In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases.
Iron overload is considered to be associated with various complications in patients who undergo both allogeneic (allo) and autologous hematopoietic stem cell transplantation (HSCT). A total of 23 ...alloHSCT recipients who started deferasirox treatment due to hyperferritinemia (ferritin ≥1,000 ng/mL) were analyzed retrospectively. The demographic characteristics, data about deferasirox treatment, and history of phlebotomy were obtained from the patients’ files. The reduction in posttreatment ferritin levels was found statistically significant compared with pretreatment ferritin levels in both def+phlebotomy and def+nonphlebotomy groups (
p
= 0.025 and 0.017, respectively). The liver enzymes, especially ALT and bilirubins, were significantly reduced after the treatment (
p
< 0.05). The deferasirox treatment reduced pretreatment ferritin levels below the level of 1,000 ng/mL in a median period of 94 days, and these data were found to be statistically significant (
p
< 0.05). The median treatment duration time with deferasirox was 94 days (72–122). The most common adverse effects were nausea and vomiting, which occurred in three of the patients (13%). In conclusion, our data suggest that oral deferasirox treatment may be used as a safe and effective alternative method for reducing iron overload in alloHSCT recipients, whether combined with or without phlebotomy.
Abstract 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.
The aim of the present study was to define the possible association between blood parameters and hair iron concentration in patient groups showing a difference in body iron content. The study ...population comprised subjects with iron deficiency anaemia and transfusion-related anaemia with different body iron contents and a healthy control group. All the cases included in the study were examined with respect to hair iron concentration, serum iron, total iron-binding capacity (TIBC), transferrin saturation and erythrocyte markers in the total blood count with ferritin values. Differences in hair iron concentration were evaluated between the groups. Correlation analysis was applied to define the association between the laboratory values used as markers of body iron content and hair iron concentration. A statistically significant difference was determined in hair iron 56Fe and 57Fe concentrations between the group with transfusion-related anaemia, the iron deficiency anaemia group and the healthy control group (P<0.001). In addition, a positive correlation was determined between hair iron 56Fe and 57Fe concentrations and serum iron, ferritin level, transferrin saturation, mean erythrocyte volume and mean erythrocyte haemoglobin values and a negative correlation with TIBC. In conclusion, the results of the present study showed a statistically significant difference in the hair iron concentrations of the patient groups with different body iron content and these values were correlated to the laboratory markers of body iron content.
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.
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