Protective role of olive oil extract of propolis on short and long-term administration of tamoxifen in rats.

Tamoxifen (TAM) is an antiestrogenic agent used for adjuvant treatment in estrogen receptor-positive breast cancers in the pre/post-menopausal period. This study, it was aimed to determine the effect of olive oil extract of propolis (OEP) on short and long-term administration of TAM in rats. Wistar albino rats were divided into groups with eight animals in each. Groups: control, OEP, TAM, and OEP + TAM. At the end of the experiment, oxidative stress tests were performed with Enzyme-Linked ImmunoSorbent Assay (ELISA) on blood and tissue samples (liver, kidney, and ovary) taken from rats. After single-dose TAM administration, there was a significant increase in red blood cell, hematocrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration levels compared to the control group, a decrease in low-density lipoprotein (LDL) value, a significant increase in liver enzymes and fasting glucose values was detected compared with the control and propolis groups. A normalizing effect was observed in the group given OEP and TAM combined. The increase in Malondialdehyde (MDA) and the decrease in enzyme activities in tissues are also noteworthy. Propolis application reduced the tissue damage caused by TAM. In addition, improved cytokine levels, which increased with TAM administration. It has been concluded that OEP can be given in supportive treatment, as it improves hematological and antioxidant parameters in TAM treatment.

Safety and efficacy of mesenchymal stromal cell therapy for multi-drug-resistant acute and late-acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

Graft versus host disease (GvHD) remains a significant risk for mortality and morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). A growing literature supports successful applications of mesenchymal stromal cells (MSCs) for the treatment of steroid-refractory acute GvHD (aGvHD). However, there is limited knowledge about the effects of MSC treatment on late-acute GvHD (late aGvHD). In this article, we present our multicenter study on the safety and efficacy of MSC therapy for patients with steroid-refractory late aGvHD in comparison to those with aGvHD. The outcome measures include non-relapse mortality (NRM) and survival probability over a 2-year follow-up. The study includes a total of 76 patients with grades III-IV aGvHD (n = 46) or late aGvHD (n = 30), who had been treated with at least two lines of steroid-containing immunosuppressive therapy. Patients received weekly adipose or umbilical cord-derived MSC infusions at a dose of median 1.55 (ranging from 0.84 to 2.56) × 106/kg in the aGvHD group, and 1.64 (ranging from 0.85 to 2.58) × 106/kg in the late aGvHD group. This was an add-on treatment to ongoing conventional pharmaceutical management. In the aGvHD group, 23 patients received one or two infusions, 20 patients had 3-4, and three had ≥ 5. Likewise, in the late aGvHD group, 20 patients received one or two infusions, nine patients had 3-4, and one had ≥ 5. MSC was safe without acute or late adverse effects in 76 patients receiving over 190 infusions. In aGvHD group, 10.9% of the patients had a complete response (CR), 23.9% had a partial response (PR), and 65.2% had no response (NR). On the other hand, in the late aGvHD group, 23.3% of the patients had CR, 36.7% had PR, and the remaining 40% had NR. These findings were statistically significant (p = 0.031). Also, at the 2-year follow-up, the cumulative incidence of NRM was significantly lower in patients with late aGvHD than in patients with aGvHD at 40% (95% CI, 25-62%) versus 71% (95% CI, 59-86%), respectively (p = 0.032). In addition, the probability of survival at 2 years was significantly higher in patients with late aGvHD than in the aGvHD group at 59% (95% CI, 37-74%) versus 28% (95% CI, 13-40%), respectively (p = 0.002). To our knowledge, our study is the first to compare the safety and efficacy of MSC infusion(s) for the treatment of steroid-resistant late aGVHD and aGVHD. There were no infusion-related adverse effects in either group. The response rate to MSC therapy was significantly higher in the late aGvHD group than in the aGvHD group. In addition, at the 2-year follow-up, the survival and NRM rates were more favorable in patients with late aGVHD than in those with aGVHD. Thus, the results are encouraging and warrant further studies to optimize MSC-based treatment for late aGVHD.

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey.

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.

The impact of diabetes mellitus on hematopoietic stem cell mobilization, a-single center cohort study.

BACKGROUND: Factors such as age, underlying hematological disease, chemotherapy and radiotherapy used, and bone marrow infiltration may cause mobilization failure. Several preclinical observed that diabetes mellitus (DM) leads to profound remodeling of the hematopoietic stem cell (HSC) niche, resulting in the impaired release of HSCs. We aim to examine the effect of DM on HSC mobilization and to investigate whether there is a relationship between complications developing in the DM process and drugs used to treat DM and mobilization failure. METHODS: In Erciyes University Bone Marrow Transplantation Unit, 218 patients who underwent apheresis for stem cell mobilization between 2011 and 2021 were evaluated retrospectively. One hundred and nine patients had a diagnosis of DM, and 109 did not. RESULTS: Mobilization failure developed in 17 (15.6 %) of the patients in the DM group, while it developed in 7 (6.4 %) patients in the non-DM group (p = 0.03). CD34+ stem cell count was 8.05 (1.3-30.2) × 106/kg in the DM group, while it was 8.2 (1.7-37.3) × 106/kg in the other group (p = 0.55). There was no statistically significant relationship between glucose and hemoglobin A1c levels and the amount of CD34+ cells (p = 0.83 and p = 0.14, respectively). Using sulfonylurea was the only independent predictor of mobilization failure (OR 5.75, 95 % CI: 1.38-24.05, p = 0.02). CONCLUSION: DM should be considered a risk factor for mobilization failure. Further research is needed fully to understand the mechanisms underlying the mobilization failure effects of sulfonylureas and to develop strategies to improve stem cell mobilization in diabetic patients.

Plerixafor in autologous stem cell transplantation: Does it affect engraftment kinetics?

Plerixafor increases stem cell mobilization by reversibly binding to the chemokine receptor CXCR4. In our study, we examined the results of mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) and revealed their effects on autologous stem cell transplantation (ASCT) engraftment kinetics. The study included all cases of ASCT performed in the Adult Bone Marrow Transplantation Unit of xxx University between January 2014 and January 2022. It included a total of 300 patients. The total number of CD34 + cells collected was 7.44 ± 4.19 in patients with plerixafor and 9.53 ± 6.09 in patients without plerixafor. The mean neutrophil and platelet engraftment took longer in plerixafor-mobilized patients (neutrophil: 12 ± 4.1 vs. 10.2 ± 2.7 days; platelet: 21.6 ± 13.9 vs. 14.2 ± 5.9 days; p = 0.008 and p = 0.002). The number of febrile neutropenia attacks was significantly higher in plerixafor-mobilized patients (p = 0.04). In the chemo-mobilized patient subgroup, plerixafor-mobilized patients experienced more febrile neutropenia attacks (p = 0.04). The mean time to both neutrophil and platelet engraftment was longer in patients mobilized with plerixafor. In the subgroup of patients with MM, the mean time to platelet engraftment was longer in patients mobilized with plerixafor. Plerixafor and its effect on engraftment kinetics should be evaluated with further studies in a larger population with survival analysis.

Extracorporeal photopheresis in the treatment of acute and chronic graft-versus-host disease: A position statement from the Turkish Society of Apheresis (TSA).

Graft versus host disease (GVHD) is still the most important cause of mortality and morbidity after allogeneic stem cell transplantation. Though perfect response rates are not achieved, steroids are still the first-line treatment. In the face of the presence of the drugs approved by FDA in recent years for acute and chronic GVHD as second-line therapy in the steroid-refractory group, there exists no standard approach. Extracorporeal photopheresis (ECP) with an immunomodulatory effect, is favored in the treatment of both acute and chronic steroid refractory GVHD as it does not increase the risk of relapses or infections. Having a low profile of side effects, ECP is also generally well-tolerated by patients. Being a time requiring procedure, the fact is that it is not able to be practiced in all health centers and requires central venous catheters in patients unfit for venous access may be enumerated among its shortcomings. No complete standard is available with respect to ECP application frequency-time; it varies from one center to another. The Turkish Society of Apheresis established the Turkish ECP (TECP) group and sought some answers to the questions regarding the use of ECP in the treatment of GVHD, and issued a position statement.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microanjiopathy (TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter study aimed to define the distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as having acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 80 patients (women: 50; man: 30) with a median age of 48 (20-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 29 (36.2 %), 22 (27.5 %), 23 (28.8 %) and 6 (7.5 %) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

Evaluation of COVID-19 fear and quality of life in patients with haematopoietic stem cell transplantation during the COVID-19 pandemic.

OBJECTIVE: We aimed to determine the coronavirus disease 2019 (COVID-19) fear state in haematopoietic stem cell transplant patients and to examine its relationship with quality of life. METHODS: In this prospective study, 64 patients who underwent HSCT during the pandemic were included. The COVID-19 fear situation was evaluated with the Fear of COVID-19 Scale (FCV-19S). Quality of life was evaluated with the European Organisation for Quality of Life Research and Treatment Core Questionnaire (EORTC QLQ-C30) (Version 3). RESULTS: The median FCV-19S score was 16.5 (12.0-22.0). The FCV-19S score was significantly higher in urban residents than rural residents. The general health score was 59.64 ± 20.04. The strongest positive correlation between fear level and life quality was found in emotional function. A weak, significant, positive correlation was observed between role function, nausea-vomiting, pain, appetite loss and fear level. CONCLUSION: FCV-19S is a quick, safe and valid tool that can be used to determine the COVID-19 fear level in vulnerable patient groups such as HSCT patients and to direct them to the necessary psycho-oncological support.

Brentuximab vedotin consolidation therapy after autologous stem-cell transplantation in patients with high-risk Hodgkin lymphoma: Multicenter retrospective study.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease <12 months (n = 61), lack of complete response (CR) to the last salvage regimen (n = 51), and having had at least two salvage regimens (n = 29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55-0.77) and 87.61% (95% CI: 0.76-0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV-naïve and BV-exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55-0.75) with an acceptable toxicity profile.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microangiopathy(TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter (n:18) study aimed to define distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for a presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 97 patients (female: 60; male: 30) with a median age of 48 (18-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 32 (33 %), 33 (34 %), 26 (27 %) and 6 (6%) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

Efficacy of therapeutic plasma exchange in patients with Crimean-Congo hemorrhagic fever.

OBJECTIVE: To examine the efficacy of therapeutic plasma exchange (TPE) in patients critically ill with Crimean-Congo hemorrhagic fever (CCHF). METHODS: Patients with CCHF received supportive treatment (ST) or TPE. After laboratory and clinical evaluations, the patients were divided into mild, moderate, and severe CCHF groups according to the severity score index (SSI). To assess the efficacy of TPE, the incubation period, time of admission to hospital, hospitalization duration, mortality rate and times to recovery of the platelet count and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were compared between patients receiving ST and TPE. RESULT: A total of 119 confirmed CCHF cases was analyzed. The median SSIs were 7 in the TPE group and 5 in the ST group. The SSI stages, median incubation times and admission times were similar in the two groups. However, the duration of hospitalization was longer in the TPE group. The overall mortality rates were 9% (3 of 33 patients) in the TPE group and 16% (5 of 31 patients) in the ST group; the difference was significant. The platelet count recovered after a median of 6 (4-7) days in the ST group. CONCLUSION: The mortality rate was lower in the TPE group than in the ST group, but the duration of hospitalization and the time to platelet recovery were longer in the TPE group than in the ST group. TPE did not contribute significantly to the prognosis of patients with intermediate-severity CCHF. However, TPE might be efficacious in patients with severe CCHF.

The use of high-flow nasal oxygen vs. standard oxygen therapy in hematological malignancy patients with acute respiratory failure in hematology wards

Background/aim: High flow nasal cannula (HFNC) was mostly used in intensive care units (ICUs) with few studies in other departments. We hypothesized that HFNC applied at wards is beneficial for acute respiratory failure in hematological malignancy patients. Materials and methods: The study is a single center, randomized controlled study. Inclusion criteria were hypoxemic respiratory failure and hematological malignancy. Patients were randomized to either venturi mask/nasal cannula oxygen treatment or HFNC. Results: One hundred patients were included in the study. Median age was 58.5 (18­86) years and APACHE II score was 17 (5­29). HFNC group was 51 patients and the oxygen treatment group 49 patients. P/F ratios were similar between the groups throughout the study period. Endotracheal intubation was required in 10 (20.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group (p = 0.14). A total of 17 (35.0%) patients in oxygen group and 17 (33.0%) patients in HFNC group received noninvasive mechanical ventilation (p = 0.97). Median VAS comfort scores at the 2nd and 24th hours were not different between groups. The 28-day mortality rate was 36.7% (18 deaths) in the standard group and 45.0% (23 deaths) in the HFNC group (p = 0.39). Conclusion: HFNC applied in wards is not superior to standard oxygen treatment for acute respiratory failure in hematological malignancy patients.

Association of uric acid levels before start of conditioning with mortality after allogeneic hematopoietic stem cell transplantation - a prospective, non-interventional study of the EBMT Transplant Complication Working Party.

Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline comorbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, P=0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, P<0.0001) and progression free survival (HR 1.6, 95% CI: 1.1-2.4, P=0.025). Non-relapse mortality was significantly increased in alloSCT recipients with high uric acid levels (HR 2.7, 95% CI: 1.4-5.0, P=0.003). Finally, the incidence of relapse after alloSCT was increased in patients with higher uric acid levels (HR 1.6, 95% CI: 1.0-2.5, P=0.04). We conclude that high uric acid levels before the start of conditioning correlate with increased mortality after alloSCT.

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.

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.

Low-dose cyclophosphamide and granulocyte colony-stimulating factor are sufficient for peripheral blood stem cell mobilization in patients with multiple myeloma.

Autologous stem cell transplantation (ASCT), supported by high-dose chemotherapy, is the prevalent option for multiple myeloma (MM) treatment in candidates suitable for transplantation. Although granulocyte colony-stimulating factor (G-CSF) supported cyclophosphamide (CY) is used as the pre-ASCT mobilization regimen, there is no consensus on the optimal dosage of CY. Thus, in this study, we examined the results of 47 MM patients, who underwent ASCT after mobilization with intermediate (ID) or low-dose (LD) CY treatment supported with G-CSF. As the mobilization regimen, we used ID (2.4 g/m2) of CY in 22 patients, and LD (1 g/m2) of CY in 25 patients. Adequate doses of CD34+ cells were collected in both groups. At the same time, febrile neutropenia was observed to be less common in patients in the LD-CY group. Additionaly 96% of patients in LD-CY group did not need to be hospitalized during the mobilization. In conclusion, we think that mobilization with LD-CY and G-CSF is advantageous since it results in a sufficient amount of stem cells in addition to being advantageous in terms of patient safety and cost.

[Investigation of Ganciclovir Resistance in Cytomegalovirus Strains Obtained from Immunocompromised Patients]. / Immün Yetmezlikli Hastalardan Elde Edilen Sitomegalovirüs Izolatlarindaki Gansiklovir Direncinin Arastirilmasi.

CMV is a virus that is asymptomatic in healthy individuals but can cause serious mortality and morbidity in transplant patients and patients with acquired immunodeficiency syndrome (AIDS). Ganciclovir (GCV) is a nucleoside analog that significantly reduces morbidity and mortality in CMV-related infections and is used as the first choice in treatment. It is the first drug shown to be effective in the treatment of CMV disease in humans, and is also homologous to acyclovir. Long-term antiviral therapy is required to prevent or treat CMV disease, but this can cause antiviral resistance which was reported to be 8-14% in CMV. In CMV strains, GCV resistance is most common in the UL97 kinase gene region. The aim of this study was to investigate GCV resistance in CMV strains obtained from the patients with immune deficiency. A total of 49 patients, including 20 children, 29 adults, who were followed in the department of hematology were included in the study. Fifty-three samples from 49 patients with CMV DNA viral load ≥ 103 copies/ml were examined for GCV resistance. In the study, DNA sequences were determined by Sanger sequence analysis method 3500 Abi Prism Genetic Analyser (Applied Biosystems, Thermo Fisher Scientific, USA) in the 674 bp part of the UL97 gene region. The next generation sequencing (NGS) method was applied to the samples that could not be evaluated with this method. GCV resistance was not detected in 35 (66%) of 53 samples with the Sanger method. C592G, C607S and M460I GCV resistance mutation was detected in three patients. Since the sequences were mixed, resistance analysis could not be evaluated with Sanger in 15 patient samples and the resistance was not detected in these samples studied with NGS. Antiviral resistance mutation was detected in three of 49 patients (6.1%). In 20 patients included in the study, three variant sequences (A442G, C592F, A427V) reported in the literature and determined to be sensitive to drugs by phenotypic tests and 78 variant sequences that were not reported in the literature were detected. As a result, the detection of antiviral resistance is important in the follow-up of the patients and guides the clinician in planning of the treatment. It was concluded that the samples that could not be evaluated with the Sanger method should be studied with NGS and further studies are needed to determine the role of the variant sequences detected for the first time in drug resistance.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Outcomes for haematological cancer patients admitted to an intensive care unit in a university hospital.

BACKGROUND: Haematological cancer (HC) patients are increasingly requiring intensive care (ICUs). The aim of this study was to investigate the outcome of HC patients in our ICU and evaluate 5 days-full support as a breakpoint for patients' re-assessment for support. METHODS: Retrospective study enrolling 112 consecutive HC adults, requiring ICU in January-December 2015. Patients' data were collected from medical records and Infection Control Committee surveillance reports. Logistic regression analysis was performed to identify independent risk factors for ICU mortality. RESULTS: Sixty-one were neutropenic, and 99 (88%) had infection at ICU admission. Acute myeloid leukaemia was diagnosed in 43%. Thirty-five (31%) were hematopoietic stem cell transplant recipients. Only 17 (15%) were in remission. Eighty-nine underwent mechanical ventilation on admission. Fifty-three patients acquired ICU-infection (35 bacteremia) being gram negative bacteria (Klebsiella pneumoniae and non-fermenters) the top pathogens. However, ICU-acquired infection had no impact on mortality. The overall ICU and 1-year survival rate was 27% (30 patients) and 7% (8 patients), respectively. Moreover, only 2/62 patients survived with APACHE II score ≥25. The median time for death was 4 days. APACHE II score ≥25 [OR:35.20], septic shock [OR:8.71] and respiratory failure on admission [OR:10.55] were independent risk factors for mortality in multivariate analysis. APACHE II score ≥25 was a strong indicator for poor outcome (ROC under curve 0.889). CONCLUSIONS: APACHE II score ≥25 and septic shock were criteria of ICU futility. Our findings support the full support of patients for 5 days and the need to implement a therapeutic limitations protocol.