Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Immune Thrombotic Thrombocytopenic Purpura in Elderly Patients: The Roles of PLASMIC and French Scores

Objective: In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. Materials and Methods: We performed a retrospective cross-sectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a single-center analysis of younger patients presenting with thrombotic microangiopathy. Results: Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). Conclusion: For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results.

The effect of cryopreservation on engraftment kinetics in fully matched allogeneic stem cell transplantation: Real-life data and literature review.

INTRODUCTION: The standard approach for allogeneic stem cell transplantation (allo-SCT) is to administer donor cells on the same day as a fresh product to a patient who has been given a preparative regimen. The difficulty in collecting and transporting donor cells, especially during the COVID-19 pandemic, has made it essential to collect and cryopreserve the grafts before the recipient begins the transplant preparation regimen. However, the short- and long-term impacts of cryopreservation on transplant outcomes remain controversial. MATERIALS AND METHODS: This retrospective study included 93 patients who underwent allo-SCT between January 2012 and August 2022 at the Stem Cell Transplant Unit of Bursa Uludag University Faculty of Medicine using frozen and fresh products of peripheral blood stem cells from a fully matched sibling donor. The effect of cryopreservation of donor grafts on engraftment kinetics was investigated. RESULTS: Frozen and fresh products were used in 37 and 56 patients, respectively. The majority of patients had acute myeloid leukemia and acute lymphoblastic leukemia. The median age at transplantation was 41 years. Neutrophil engraftment time was similar between the two groups (median: 14 vs. 16 days, p = 0.393). Platelet engraftment time was longer in the frozen product group (median: 12 vs. 15 days, p < 0.001). There was no statistically significant difference between freezing time and viability. The acute graft-versus-host disease (GVHD) rate was 37.8 % in the frozen product group and 28.6 % in the fresh product group (p = 0.349). There was no significant difference between the two groups in terms of primary and secondary graft failure, chronic GVHD, 30-day chimerism, relapse, overall survival, progression-free survival, and nonrelapse mortality. CONCLUSION: Having donor cells ready before transplantation significantly prevents donor-induced adverse events and provides confidence and practicality to both the clinician and the recipient. Allo-SCT with frozen products is a successful method that can be safely applied, especially when disruptions in donor-derived cell collection or transportation are foreseen.

Systemic inflammatory indices for predicting prognosis of myelofibrosis.

The impact of inflammatory markers such as systemic immune-inflammation (SII) index and systemic inflammation response index (SIRI) on myelofibrosis (MF) prognosis was evaluated for the first time in this study. Data from 60 patients diagnosed with MF between March 2011 and September 2022 were retrospectively analyzed. In addition to disease-related markers, the impact of SII and SIRI on prognosis was evaluated. In our study, the overall median survival (OS) was 64 months. OS was significantly shorter in patients older than 65 years, with high ferritin and lymphocyte levels, transfusion dependence at diagnosis, platelet count below 100 × 109/L, Hb level below 8 g/dl, and high risk according to the dynamic international prognostic scoring system (DIPSS)-Plus score. When these variables were included in the multivariate Cox regression model, it was found that being older than 65 years, having a high ferritin value, being at high risk according to the DIPSS-plus score and Hb values below 8 increased the risk of death. Platelet-to-lymphocyte ratio (PLR) and SII index were lower in patients with a fatal outcome. No statistically significant relationship was found between SIRI and mortality. The findings of this study showed that low PLR and high ferritin were associated with poor prognosis in MF. Elevated SII and SIRI, evaluated for the first time in patients with myelofibrosis, did not predict prognosis. Since non-inflammatory variables play a role in the pathogenesis of MF, bone marrow indicators and systemic inflammation indicators derived from hematologic parameters may not be accurate.

Potential modifications of the PLASMIC scoring system for predicting thrombotic thrombocytopenic purpura: Sometimes, less is more.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening occlusive disease of the microcirculation characterized by systemic platelet plugs, organ ischemia, deep thrombocytopenia, and fragmentation of erythrocytes. One of the widely used scoring system to determine the clinical probability of TTP is the PLASMIC scoring system. This study aimed to evaluate the contribution of PLASMIC score modifications to sensitivity and specificity in patients with microangiopathic hemolytic anemia (MAHA) undergoing plasma exchange with a prediagnosis of TTP at our center. MATERIALS AND METHODS: The data of patients who were hospitalized with a previous diagnosis of MAHA and TTP and underwent plasma exchange at Bursa Uludag University, Faculty of Medicine, Department of Hematology between January 2000 and January 2022 were retrospectively analyzed. RESULTS: Overall, 33 patients (including 15 and 18 with and without TTP, respectively) were included in this study. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for the original PLASMIC score was 0.985 (95% confidence interval [95% CI]: 0.955-1.000), and AUC for the PLASMIC score without mean corpuscular volume (MCV) was 0.967 (95% CI: 0.910-1.000), which is close to the original AUC. With the removal of MCV from the scoring system, the sensitivity decreased from 100% to 93%, whereas the specificity increased from 33% to 78%. CONCLUSIONS: Based on the results of this validation study, removing MCV from the PLASMIC score led to the categorization of eight non-TTP cases in the low-risk category, and this could avoid unnecessary plasma exchange. However, in our study increasing the specificity was at the expense of the sensitivity by missing one patient with this new scoring system without MCV. Further multicenter studies with large sample sizes are required owing to the fact that different parameters may be effective in TTP prediction among different populations.

The effect of the time from diagnosis to induction therapy on prognosis in patients with acute leukemia undergoing leukapheresis for symptomatic hyperleukocytosis.

INTRODUCTION: Our study investigated leukapheresis's effect on delayed induction therapy outcomes in patients with acute leukemia presenting with symptomatic hyperleukocytosis. METHODS: This retrospective cohort study included 30 adult patients diagnosed with acute leukemia who underwent leukapheresis for leukostasis. The patients were divided into the first 24 h and >24 h groups, according to the time from diagnosis to induction therapy (TDT). RESULTS: There was no significant difference between the TDT groups regarding complete remission (CR), 4-week mortality, and overall survival (OS) at a median follow-up of 409 days. Tumor lysis syndrome, disseminated intravascular coagulation, and hemoglobin levels were significant in early mortality. In univariate analysis, age, hemoglobin levels, patients' eligibility for intensive chemotherapy, and achieving CR were critical factors for OS. CONCLUSION: The study findings suggest that waiting for the clinical and laboratory results may be a safe and reasonable approach before assigning patients the best treatment option with leukapheresis.

Severe Aplastic Anemia and a Healthy Pregnancy Immediately Following Syngeneic Transplantation: An Extremely Rare Case Report.

Aplastic anemia is potentially fatal, particularly if the disease does not respond to immunotherapy and progresses to severe pancytopenia. Allogeneic hematopoietic stem cell transplant from an HLA-matched sibling donor, the first-line treatment in patients younger than 40 years, is used as a curative treatment option in severe aplastic anemia. The availability of an identical twin donor is infrequent, and there is limited experience in this context. Additionally, the choices for a conditioning regimen for a syngeneic transplant to prevent engraftment failure and the necessity of graft-vs-host disease prophylaxis are controversial. Although long-term survival gradually increases after an allogeneic hematopoietic stem cell transplant, hypogonadism and infertility are the main problems that significantly affect patients' quality of life. We present a patient diagnosed with severe aplastic anemia who has had a healthy pregnancy immediately after a syngeneic transplant.

Two Cases of Kidney Transplant Recipients With Multiple Relapsing Pure Red Cell Aplasia Due to Parvovirus B19 Infection.

Although anemia is common after kidney transplant, pure erythroid aplasia due to parvovirus B19 infection is rare. Therefore, there are delays in diagnosis in transplant patients. Here, we aimed to raise awareness that pure red blood cell aplasia due to parvovirus B19 should be considered in the differential diagnosis of posttransplant anemia. Our report analyzes 2 kidney transplant recipients under immunosuppressive therapy who were diagnosed with pure red blood cell aplasia due to parvovirus B19 infection. Both patients were examined for anemia as a cause for transfusion dependence. Normochromic, normocytic anemia, and reticulocyte levels were low. Leukocyte and platelet counts and biochemical parameters were within reference ranges. Therefore, pure red blood cell aplasia associated with parvovirus B19 was included in the differential diagnosis. Bone marrow showed erythroid hypoplasia and megaloblastic changes with giant erythroblasts containing dark-stained inclusion structures. Results from the other series (neutrophils, lymphocytes, platelets) were within reference ranges. Parvovirus B19 immunoglobulin M and G levels were negative in both patients, yet serum parvovirus B19 DNA polymerase chain reaction test results were positive. Therefore, diagnosis was parvovirus B19-associated pure red blood cell aplasia. Anemia resolved completely by 4 weeks after reduction of immunosuppression and intravenous immunoglobulin. Both patients relapsed in month 5 of treatment. One patient relapsed 3 times during follow-up, with complete response to intravenous immunoglobulin for all 3 events. The second patient showed partial response to intravenous immunoglobulin after relapse. We suggest that pure red blood cell aplasia associated with parvovirus B19 should be considered in transplant patients who present with anemia and reticulocytopenia. Negative serology does not exclude the diagnosis, and it is important to perform a parvovirus B19 DNA polymerase chain reaction test. Intravenous immunoglobulin therapy is effective to cure anemia within weeks. Follow-up of patients is important because relapse may occur after treatment.

The Role of White Blood Cell Count in Perianal Pathologies: A Retrospective Analysis of Hematologic Malignancies.

Background and Objective: Infections are the most common cause of anal and perianal pathologies in patients with hematological malignancies. Perianal infection diagnosis in this group of patients is difficult; thus, a careful anorectal examination is necessary with imaging modalities. In addition, the literature reveals a knowledge gap in the approach to anal pathologies in patients with neutropenia during diagnosis or chemotherapy. This study aimed to examine our institutional data on perianal complications and investigate the relationship between the white blood cell-neutrophil count, perianal lesion, and the type of treatment in patients with hematologic malignancies during the neutropenic period. Methods: Patients with a hematologic malignancy, hospitalized for cytotoxic chemotherapy, complicated by perianal pathology, documented by at least one imaging method, were included in the study. Results: A total of 42 patients were included in the study. Most of them had acute leukemia, 31 were affected by acute myeloid leukemia (AML), and 7 by Acute lymphoid leukemia (ALL). There was no statistically significant relationship between the anal abscess formation, the neutrophil count, and a previous perianal pathology. Anal abscess development was significantly more frequent in acute myeloid leukemia. An inverse relationship was found between the total white blood cell number at onset and having a surgical intervention for anal pathology.In conclusion, this article has shown that white blood cell count at the time of hospitalization can affect the surgical intervention in patients with hematological malignancy (in the majority with acute leukemia) affected by anal pathologies occurring in the neutropenic period.

Is split-dose better than single-dose? Results of Turkish Stem Cell Coordination Center (TURKOK) donors in the era of rising biosimilar G-CSF.

BACKGROUND: Turkish Stem Cell Coordination Center (TURKOK) carries out the procurement process of unrelated allogeneic hematopoietic stem cells in Turkey. This study aims to compare the efficacy of both once-daily and divided-dose G-CSF administration and the original and biosimilar G-CSF use and the frequency and severity of adverse events in TURKOK donors. METHOD: The study was conducted retrospectively with 142 healthy TURKOK donors. For PBSC mobilization, two different subcutaneous G-CSF programs were used as 10 µ/kg/day single-dose and 5 µ/kg/12 h. Neupogen (Amgen, Puerto Rico) and Tevagrastim (Teva, Kfar Saba, Israel) were used as G-CSF. All donors started apheresis on the fifth day, and all side effects were recorded during the procedure. RESULTS: Stem cell yield was similar between single-dose and divided-doses based on donor weight, favoring the split-dose based on recipient weight (P = .506 and P = .023, respectively). Both G-CSF posologies were comparable if the target CD34+ cell yield was ≥4 × 106 /kg. CD34+ cell yield was equivalent when evaluated against recipient weight, significantly favoring Tevagrastim vs Neupogen by donor weight (P = .740 and P = .021, respectively). Side effects, duration of pain, and need for analgesia favor Tevagratim over Neupogen. CONCLUSION: Split-dose may be recommended for cases where the need for large numbers of CD34+ cells to be harvested is anticipated due to significant cell yield relative to recipient weight. However, sufficient hematopoietic stem cells can be collected with both posology. Tevagrastim is non-inferiority effective to Neupogen. Side effects during administration are both low-grade and temporary.

Evaluation of Using Empiric Glycopeptides in Accordance with the IDSA Guidelines in Hematologic Malignancy Patients with Febrile Neutropenia.

Background: This study aimed to evaluate the effects of the appropriate use of empiric glycopeptide therapy in hematologic malignancy patients with febrile neutropenia (FN). Materials and Methods: Patients with FN who were hospitalized in our clinic and started empiric glycopeptide therapy were retrospectively analyzed. Empiric glycopeptide treatment initial indications were determined according to 7 specific criteria in the IDSA guidelines. In addition, the duration of glycopeptide use according to initial indications, causative pathogens in culture positivity, frequency of VRE infection, and the mortality rate was identified. Results: 87 patients were included. Of these, 102 episodes of FN were analyzed. Appropriate use of glycopeptides was observed in 98% of patients. The most common initial indication for glycopeptide was skin or soft-tissue infection, with 52% (n = 53). The mean duration of glycopeptide use was 11 (2-22) days. The time of glycopeptide use was longer in patients with catheter-related infections than in those with severe mucositis and hemodynamic instability (p = 0,041/p = 0,016). The duration of glycopeptide use was shorter in patients with consolidation therapy than in those without consolidation therapy. The mortality rate in culture-positive patients was significantly higher than in culture-negative patients (p = 0.041). At 72 h, glycopeptide therapy was discontinued in 8 of 79 FN episodes within culture-negative patients. Conclusion: This study showed that the mortality rate was higher in culture-positive patients. Additionally, glycopeptides should be discontinued early with no evidence of gram-positive infection.

Castleman Disease: A Multicenter Case Series from Turkey

Objective: Castleman disease (CD) is a rare disease also known as angiofollicular lymph node hyperplasia. The two main histological subtypes are the hyaline vascular and plasma cell variants. It is further classified as unicentric CD (UCD) or multicentric CD (MCD) according to the anatomical distribution of the disease and the number of lymph nodes involved. The aim of this multicenter study was to evaluate all cases of CD identified to date in Turkey to set up a national registry to improve the early recognition, treatment, and follow-up of CD. Materials and Methods: Both adult (n=130) and pediatric (n=10) patients with lymph node or involved field biopsy results reported as CD were included in the study. Patients' demographic information, clinical and laboratory characteristics, imaging study results, treatment strategies, and clinical outcomes were evaluated retrospectively. Results: A total of 140 patients (69 male and 71 female) with a diagnosis of UCD (n=73) or MCD (n=67) were included. The mean age was 39 years in the UCD group and 47 years in the MCD group. Female patients were more common in the UCD group. The most common histological subtype was hyaline vascular for both UCD and MCD patients. Asymptomatic patients were more common in the UCD group. Anemia, elevations of acute phase reactants, and hypoalbuminemia were more common in the MCD group. The most commonly used treatment strategies for UCD were surgical excision, rituximab, and radiotherapy, respectively. All UCD patients were alive at a median of 19.5 months of follow-up. The most commonly used treatment strategies for MCD were methyl prednisolone, R-CHOP, R-CVP, and rituximab. Thirteen MCD patients had died at a median of 34 months of follow-up. Conclusion: This study is important in presenting the patient characteristics and treatment strategies for CD from Turkey, with the potential of increasing awareness about CD. Treatment data may help in making decisions, particularly in countries that do not have access to siltuximab. However, larger prospective studies are needed to make definitive conclusions.

The evaluation of risk factors leading to early deaths in patients with acute promyelocytic leukemia: a retrospective study.

Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients.

Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Conventional Amphotericin B Associated Nephrotoxicity in Patients With Hematologic Malignancies.

INTRODUCTION:  Amphotericin B (AmB-d) is one of the most effective therapeutic options against frequently life-threatening systemic fungal infections in patients with hematologic malignancies. However, significant adverse effects including nephrotoxicity associated with its use limit its more widespread use. The objectives of our study were to determine the incidence of AmB-d associated nephrotoxicity, to evaluate clinical and epidemiological characteristics of patients, and to support the notion that conventional amphotericin B remains a valid therapeutic option among hematologic patients with proper patient selection. MATERIALS AND METHODS: A total of 110 patients with hematologic malignancies were admitted to our Hematology Unit between January 2014 and November 2017 who required anti-fungal therapy during intensive systemic chemotherapy. The incidence of AmB-d associated nephrotoxicity, side effect profile, time to nephrotoxicity, and clinical and epidemiological characteristics associated with treatment success were assessed retrospectively. RESULTS: Of the 110 patients receiving AmB-d, 70 (63.6%) were male and 40 (36.4%) were female. The mean age of participants was 44 years. The most common diagnosis was acute myeloid leukemia (n=53, 48.2%), and the most common chemotherapy protocol was 7 + 3 remission-induction (cytarabine 100 mg/m² days 1-7, Idarubicin 12 mg/m² days 1-3; n=24, 21.8%). In 56.4% of the patients, antifungal therapy was given empirically. In 40 patients (36.4%), nephrotoxicity was observed following antifungal treatment, and only four patients had stage 3 renal failure. The mean duration of time to nephrotoxicity from initiation of amphotericin B was four days (min: 2, max: 31). All patients were found to receive at least one additional potential nephrotoxic treatment during the antifungal treatment process.  Conclusion: AmB-d is associated with a significant risk of nephrotoxicity. In most hematological patients, antifungal treatment is initiated empirically, and patients received prolonged courses of treatment. Therefore, it is plausible to initiate such treatment with AmB-d, when one considers the already high treatment costs in this patient group as well as the fact that AmB-d offers similar efficacy to antifungal agents at a lower cost. AmB-d may be recommended as a first-line agent in this patient group with the introduction of newer and more costly antifungal agents when needed, on the basis of the fact that these patients can be closely monitored in a hospital setting, reversible nature of nephrotoxicity upon discontinuation, and rare occurrence of severe renal failure requiring dialysis.

Evaluation of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab in Turkey: a multicenter retrospective analysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare X-linked genetic disorder. On the contrary to its name, it is a multisystemic disease and various symptoms other than hemoglobinuria could be occurred. It could be life threatening especially because of thromboembolic events. In the last decade, a terminal complement inhibition with eculizumab approved with promising results for PNH patients. We conducted this study to evaluate the long term experience of eculizumab therapy from Turkey for the first time. Our cohort included 138 patients with PNH treated with eculizumab between January 2008 and December 2018 at 28 centers in Turkey. Laboratory and clinical findings at the time of diagnosis and after eculizumab therapy were recorded retrospectively. The median age was 39 (range 18-84) years and median granulocyte PNH clone size was 74% (range 3.06-99.84%) at the time of diagnosis. PNH with bone marrow failure syndrome was detected in 49 patients and the rest of 89 patients had classical PNH. Overall 45 patients (32.6%) had a history of any prior thrombotic event before eculizumab therapy and only 2 thrombotic events were reported during the study period. Most common symptoms are fatigue (75.3%), hemoglobinuria (18.1%), abdominal pain (15.2%) and dysphagia (7.9%). Although PNH is commonly related with coombs negativity, we detected coombs positivity in 2.17% of patients. Seven months after the therapy, increased hemoglobin level was seen and remarkably improvement of lactate dehydrogenase level during the treatment was occurred. In addition to previous studies, our real life data support that eculizumab is well tolerated with no serious adverse events and improves the PNH related findings.

Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality. PATIENTS-METHODS: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files. RESULTS: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival. CONCLUSION: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.