Does immunohistochemical staining predict mobilization success in multiple myeloma patients?

BACKGROUND: So many risk factors for mobilization failure have been described so far. We aimed to identify the risk factors and search the possible effects of bone marrow fibrosis (BMF), CD56, c-myc, and cyclinD1 expression on mobilization. METHODS: We evaluated 189 patients with MM who were admitted for stem cell mobilization before autologous stem cell transplantation (ASCT) between 2015 and June 2021. Clinical, laboratory, treatment features, and survival outcomes were compared in patients who were successfully mobilized and who were not. RESULTS: Mobilization failure rate was 11.1 % (21) in our study group. Male gender, mobilization with only G-CSF, history of previous ASCT, lenalidomide exposure, and 2 lines of chemotherapy before stem cell mobilization were observed more commonly in mobilization failure group. There is no relationship between mobilization failure and BMF, CD56, c-myc, and cyclin D1 expression status in patients who received either only G-CSF or G-CSF+ chemotherapy for mobilization. Overall survival (OS) was not different in groups of patients who were successfully mobilized and who were not. Neutrophil engraftment was faster in patients who were transfused > 5 × 106/kg stem cells (p = 0.015). ECOG performance status (p = 0.004), c-myc expression (p = 0.005), lenalidomide therapy before mobilization (p = 0.032), and mobilization with G-CSF+chemotherapy was found to be predictive factors for OS. CONCLUSION: Even though we could not find any predictive value of CD56, c-myc, and cyclin D1 expression on mobilization, c-myc was found to be associated with low OS. Further studies with large and homogenous study population would be more informative.

Incidental Diagnosis of Cyclic Thrombocytopenia: An Asymptomatic Case.

Cyclic thrombocytopenia (CTP) is a very rare condition that is characterized by episodic thrombocytopenia over a period of three to five weeks. The pathogenesis of CTP is unclear and most likely heterogeneous; however, usually there is no clue about the underlying disease. In this case report, we presented a 48-year-old female who had a low platelet count of 66 x 103/µL (range: 150-450 x 103/µL) on her routine examination with no evidence of bleeding. On further review of her laboratory workup in the past several years, she was noted to have multiple episodes of low platelet counts. She was diagnosed with CTP after a recurrent pattern of fluctuations in her platelet count, with improvements sometimes without intervention. Unfortunately, most CTP patients are misdiagnosed as having primary immune thrombocytopenia (ITP), and CTP typically responds poorly to ITP therapy. This case underscores the need for further research and serves as a valuable reference to increase the awareness of clinicians about CTP.

Accuracy and clinical role of digital templating for total knee arthroplasty performed on haemophilic knees.

INTRODUCTION: In total knee arthroplasty (TKA), choosing the correct implant size is important. There is lack of data on accuracy of templating on haemophilic knees. Our aim was to test the accuracy of 2D digital templating for TKA on haemophilic arthropathy (HA) of knee. MATERIALS AND METHODS: TKAs performed on HA between January 2011 and January 2022 were screened. Osteoarthritis (OA) group was created as control group by a one-to-one matching regarding type of implant used. Intra- and interobserver correlations were measured in HA, then correlation between templated and implanted sizes was investigated in four assessments (femur AP, femur lateral, tibia AP, tibia lateral), then compared with OA group. Fifty-eight knees in each group included. RESULTS: Regarding intraobserver correlation in HA, there was excellent correlation for femur AP [.93 (.73-.98)], femur lateral [.98 (.91-.99)], and tibia AP (1.0) templating. Regarding interobserver correlation in HA, excellent correlation was observed for femur lateral [.93 (.74-.98)] and tibia AP templating [.90 (.65-.97)]. Regarding correlation of templated and applied sizes in HA; tibia AP, tibia lateral and femur lateral templating showed good correlation [.81 (.70-.89), .86 (.77-.91), .79 (.67-.87) while femur AP templating showed moderate correlation [.67 (.50-.79)]. Comparing HA and OA, there was no difference in correlation levels regarding femur AP, femur lateral, tibia AP and tibia lateral templating (p = .056, p = .781, p = .761, p = .083, respectively). CONCLUSION: Although 2D digital templating shows comparable correlation in HA and OA, clinical applicability of templating on HA appears to be limited in its current state.

The assessment of health-related quality of life in patients with polycythemia vera.

Previous studies have shown that patients with polycythemia vera (PV) have poor quality of life (QoL). Similarly, it has been shown that survival is influenced by QoL. We aimed to evaluate QoL in 88 Turkish patients with PV. This cross-sectional study included cases diagnosed with PV between January 1995 and August 2019 who attended follow-up studies in the hematology department of a tertiary hospital in Türkiye between August 2019 and July 2020. Beginning in August 2019, subjects who approved study participation applied the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire during their routine follow-up-given that they met inclusion/exclusion criteria. Individuals with comorbidities or factors influencing QoL and those with secondary PV-related conditions were excluded. Recorded data included age, sex, history of bleeding, thrombosis, erythrocytosis, leukocytosis, thrombocytosis, obesity or splenomegaly, and cytogenetic mutation profiles such as JAK2, BCR and MPL. We also assessed whether they needed phlebotomy or erythrocyte suspensions. Data concerning comorbidities and medication use were obtained from medical records. The median age of patients was 52 (44-61) years. The majority of participants were male (67.05%). Global health status score was 75 (66.67-83.33). PV patients who had required phlebotomy demonstrated higher social functioning scores (P = .004) and lower scores for loss of appetite (P = .013) and financial difficulties (P = .020) than patients without phlebotomy. PV patients who had suffered from leukocytosis demonstrated lower physical functioning scores compared to those without leukocytosis (P = .001). Patients without JAK2 exon 14 mutations had better physical (P = .016) and cognitive functioning scores (P = .048). It was found that PV patients with splenomegaly demonstrated lower physical functioning (P = .019) and higher appetite loss scores (P = .005) than those without splenomegaly. Higher leucocyte counts were associated with decreased physical functioning and greater fatigue. In conclusion, we demonstrated deterioration of physical and emotional QoL in patients diagnosed with PV. Patients with PV require individualized, patient-specific and integrated approaches in order to minimize symptoms, improve QoL, and increase survival.

Management of Primary Immune Thrombocytopenia: Turkish Modified Delphi-Based Consensus Statement for Special Considerations

Objective: Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with a complex and unclear mechanism of increased immune destruction or impaired production of platelets. While the management of ITP is evolving, there is still a need for guidance, particularly in certain circumstances such as pregnancy, emergencies, or patients requiring co-medications. We aimed to determine the tendencies of hematologists in Türkiye in the event of such special considerations. Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group, founded under the auspices of the Turkish Society of Hematology, developed a questionnaire consisting of statements regarding pregnancy, emergencies, and circumstances requiring co-treatment with antiaggregants or anticoagulants. A total of 107 hematologists working in university or state hospitals voted for their agreement or disagreement with the statements for two sequential rounds. Results: The participating hematologists reached an agreement on starting treatment for pregnant patients with platelets of less than 30x109/L and delivery either vaginally or by cesarean section being safe at platelet counts above 50x109/L. For emergencies and the rescue management of ITP, the panel agreed against the use of high-dose corticosteroids alone, preferring combinations with transfusions or intravenous immunoglobulin. For patients who require interventions, platelet counts of >50x109/L were regarded as safe for low-risk procedures as well as co-treatment with antiplatelets or anticoagulants. Conclusion: As the National ITP Study Group, we have observed the need to increase the practice guidance regarding patients with primary ITP requiring additional treatments including invasive interventions and co-treatments for coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to variations in practices.

Management of Adult Primary Immune Thrombocytopenia: Delphi-Based Consensus Recommendations

Objective: Primary immune thrombocytopenia (pITP) is an acquired autoimmune disorder related to the increased destruction and/or impaired production of platelets. Its diagnosis and management are challenging and require expertise and the interpretation of international consensus reports and guidelines with national variations in availability. We aimed to assess the agreement of hematologists in Türkiye on certain aspects of both first-line and second-line management of patients with pITP. Materials and Methods: Applying a modified Delphi method, the Turkish National ITP Working Group (14 steering committee members), founded under the auspices of the Turkish Society of Hematology, developed a 21-item questionnaire consisting of statements regarding the first-line and second-line treatment of pITP. A total of 107 adult hematologists working in either university or state hospitals voted for their agreement or disagreement with the statements in two consecutive rounds. Results: The participants reached consensus on the use of corticosteroids as first-line treatment and with limited duration. Methylprednisolone was the corticosteroid of choice rather than dexamethasone. Use of intravenous immunoglobulin was not preferred for patients without bleeding. It was also agreed that thrombopoietin receptor antagonists (TPO-RAs) or rituximab should be recommended as second-line treatment and that splenectomy could be considered 12-24 months after diagnosis in patients with chronic pITP. Conclusion: The optimization of the dose and duration of TPO-RAs in addition to corticosteroids is necessary to improve the management of patients with pITP.

Morphological analysis of patellofemoral joint in haemophilic arthropathy: A case-control study.

INTRODUCTION: Knees affected by haemophilic arthropathy exhibit distinct differences in both bone morphology and soft tissue behaviour. This study aims to analyse the morphological characteristics of the distal femur and patellofemoral joint in patients with haemophilia in comparison to normal healthy population. MATERIAL AND METHODS: Study was conducted as pair-matched case-control study with 43 individuals in both the haemophilia group and the control group. Patellar luxation, patellar tilt (PT), length of the patella in both axis (pAP, pML), depth and angle of trochlear sulcus (SD, SA), lateral trochlear inclination (LTI), medial and lateral femoral facet length (mFL, LFL), intercondylar depth (ID), transepicondylar axis (TEA) and lateral condyle length (LCL) were assessed on knee MRI. Correlation between Pettersson score and measured variables were also analysed. RESULTS: PT was medial sided in 10 (23.2%) cases in haemophilic group. Mean values of pAP, pML, PT were significantly lower in haemophilia group (p < .001, p: .007, p = .001 respectively). There were no significant changes in SA (p = .628), SD (p = .340), LTI (p = .685), LFL (p = .241) and MFC-LFC (p = .770) whilst mFL was significantly longer in haemophilia group (p = .009). ID (p < .001), TEA (p = .007) and LCL (p = .001) were all shorter in haemophilia group. Pettersson score was inversely correlated with pAP, pML, ID, TEA, LCL, pML/SA and ID/LCL. CONCLUSION: Morphological changes in haemophilic arthropathy involve a smaller and medially-tilted patella, narrowed lateral condyle and transepicondylar axis, combined with reduced intercondylar depth. These alterations must keep in mind especially in pre- and intraoperative assessments for arthroplasty procedures.

Adherence to hemophilia patients with prophylaxis: Veritas-Pro and psychometric properties adapted to Turkish.

The Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis (VERITAS-Pro) assesses adherence to prophylaxis treatment recommendations in hemophilia patients. This study aimed to adapt the VERITAS-Pro into Turkish and evaluate its reliability and validity. The research design used is a psychometric study. A convenience sample of 102 patients with hemophilia A or B was followed by the Aegean Adult Hemophilia and Thrombosis Center. The VERITAS-Pro was adapted to Turkish in six steps, including forward- and back-translation, committee review, and reliability and validity analysis. Based on the confirmatory factor analysis, modification indices suggested discrepancies amongst items, which were improved upon the removal of items 11 and 15. Findings from this alternative model are: χ2/df = 1.34; RMSEA = 0.05; SRMR = 0.09; and IFI = 0.92. The alternative model showed high adherence rates. Cronbach's alpha value for the Turkish version was found to be 0.83. The test-retest reliability of the Turkish scale ranged from 0.31 to 0.78. All items discriminated significantly between participants who were more adherent and those who were less adherent (t = 23.53; p<0.01). Translation of the VERITAS-Pro into local languages enables more accurate measurement of treatment adherence among people with hemophilia and facilitates cross-cultural comparison studies. According to the validity and reliability evidence obtained, the psychometric properties of the Turkish version of the VERITAS-Pro are suitable.

Level of Awareness of Acquired Hemophilia A Among Physicians in Türkiye: A Survey Study

This survey study aimed to evaluate the level of awareness and knowledge of acquired hemophilia A (AHA) among physicians from various specialties. Data were collected by administering a questionnaire containing questions about two patient profiles to evaluate the approaches of physicians from different specialties. The study included a total of 945 physicians. The most common suspected diagnosis for the clinical patient profile was immune thrombocytopenia, followed by hemophilia. For the laboratory patient profile, the most common suspected diagnosis was hemophilia. While only 9.4% of the physicians stated that they had good knowledge of this disease, only 21.6% wanted to learn more about AHA. Most of the participating physicians do not rank AHA first in the differential diagnosis of a patient with clinical and laboratory findings of AHA. Appropriate educational activities to raise awareness of AHA will help reduce disease-related morbidity and mortality.

Adult Onset Langerhans Cell Histiocytosis: Clinical Characteristics and Treatment Outcomes.

PURPOSE: Langerhans cell histiocytosis (LCH) is a rare disease that can affect all tissues and organs. Our study evaluated the clinical characteristics and treatment outcomes of adult-onset LCH patients in a tertiary center. MATERIALS AND METHODS: Adult patients diagnosed with LCH were retrospectively evaluated. Their initial symptoms, stratification according to disease involvement, treatment details, treatment responses, and overall and progression-free survival (PFS) were analyzed. RESULTS: Thirty-three patients were included. There were 21 single system LCH, 10 multisystem LCH, and 2 pulmonary LCH patients. Patients with single system unifocal involvement were successfully treated with local therapies such as surgery and radiotherapy. Most of the multisystem LCH patients and patients with single system multifocal involvement were treated with systemic chemotherapy. Cladribine was the first choice in 10 out of 11 patients who received chemotherapy. Among all patients, the overall response rate (ORR) was 97%. Among those who had cladribine in the first-line the ORR was 81%. All these patients achieved a complete remission and were alive at the last visit. The median follow-up was 38 (range, 2-183) months. The median PFS has not yet been reached. Ten-year PFS was 90.9%. CONCLUSION: Besides successful local treatments with surgery and radiotherapy, our study provides information for front-line cladribine treatment.

Acquired Hemophilia A In Adults: A Multicenter Study from Turkey.

Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies inhibiting factor VIII (FVIII) activity. Although the conditionis usually idiopathic, there may be other underlying diseases. Treatment consists of two steps: treatment of acute bleeding and immunosuppression. In this multicenter study, we aimed to demonstrate the clinical characteristics, management details, and survival of AHA patients in Turkey. Data was collected from eleven centers in Turkey. aPTT, FVIII, FVIII inhibitor, and hemoglobin (HB) levels, mixing test results, and demographics at diagnosis, treatment information, adverse events, bleeding episodes during follow-up, relapses, and outcome were analyzed. Twenty-nine patients were analyzed (58.6% female). No underlying disorder could be detected in 14 patients. The most prevalent etiologies were pregnancy, malignancy and infections. The median FVIII activity and FVIII inhibitor titer at diagnosis were 0.7% (0.0-29.4%) and 32.6 BU (0.6-135.6 BU) respectively. Bleeding was severe in 44.8% of patients. The HB value was significantly lower in patients with severe bleeding. Most of the patients (n = 25, 86.2%) had only one bleeding episode without relapse, three patients (10.3%) had two bleeding episodes, and one patient had more than three bleedings. 21 (75%) patients received hemostatic therapy. The use of recombinant FVIIa was slightly higher than activated prothrombin complex concentrate (15 versus 10 patients). Immunosuppressive treatment was initiated in 26 (93%) patients. Regimens containing steroid, cyclophosphamide, and rituximab in different combinations were the most preferred. The median follow-up period was 13 months (2-156 months). Median overall survival was 154.97 months. Four and six-year survival were 90.9 ± 0.8% and 77.9 ± 14.1% respectively. This is a unique study that investigated the demographic characteristics, treatment approaches, and patient survival of AHA in Turkey.

Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up.

INTRODUCTION: This study compared the pharmacokinetics (PK) of the ravulizumab on-body delivery system for subcutaneous (SUBQ) administration with intravenous (IV) ravulizumab in eculizumab-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS: Patients with PNH received SUBQ ravulizumab (n = 90) or IV ravulizumab (n = 46) during the 10-week randomized treatment period; all patients then received SUBQ ravulizumab during an extension period (< 172 weeks; data cutoff 1 year). Primary endpoint was day 71 serum ravulizumab trough concentration (Ctrough). Secondary endpoints were ravulizumab Ctrough and free C5 over time. Efficacy endpoints included change in lactate dehydrogenase (LDH), breakthrough hemolysis (BTH), transfusion avoidance, stabilized hemoglobin, and Treatment Administration Satisfaction Questionnaire (TASQ) score. Safety, including adverse events (AEs) and adverse device effects (ADEs), was assessed until data cutoff. RESULTS: SUBQ ravulizumab demonstrated PK non-inferiority with IV ravulizumab (day 71 SUBQ/IV geometric least-squares means ratio 1.257 [90% confidence interval 1.160-1.361; p < 0.0001]). Through 1 year of SUBQ administration, ravulizumab Ctrough values were > 175 µg/mL (PK threshold) and free C5 < 0.5 µg/mL (PD threshold). Efficacy endpoints remained stable: mean (standard deviation, SD) LDH percentage change was 0.9% (20.5%); BTH events, 5/128 patients (3.9%); 83.6% achieved transfusion avoidance; 79.7% achieved stabilized hemoglobin. Total TASQ score showed improved satisfaction with SUBQ ravulizumab compared with IV eculizumab (mean [SD] change at SUBQ day 351, - 69.3 [80.1]). The most common AEs during SUBQ treatment (excluding ADEs) were headache (14.1%), COVID-19 (14.1%), and pyrexia (10.9%); the most common ADE unrelated to a device product issue was injection site reaction (4.7%). Although many patients had ≥ 1 device issue-related ADE, full SUBQ dose administration was achieved in 99.9% of attempts. CONCLUSIONS: SUBQ ravulizumab provides an additional treatment choice for patients with PNH. Patients may switch to SUBQ ravulizumab from IV eculizumab or ravulizumab without loss of efficacy. TRIAL REGISTRATION: NCT03748823.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by the destruction of red blood cells (hemolysis) within blood vessels. In addition to hemolysis, patients with PNH are susceptible to life-threatening blood clots (thromboses). Eculizumab and ravulizumab are types of treatments for PNH, called C5 inhibitors. In the blood, these treatments bind to C5 protein and prevent the destruction of red blood cells, reducing the symptoms and complications of PNH. Both treatments are approved for use via intravenous (through the vein) administration. Ravulizumab is also approved in the USA for use via subcutaneous (under the skin) administration. This study compared subcutaneous ravulizumab with intravenous ravulizumab in patients with PNH who had previously been treated with eculizumab. During the initial treatment period of 71 days, 90 patients received subcutaneous ravulizumab and 46 received intravenous ravulizumab. Following this period, all patients received subcutaneous ravulizumab. At day 71, the amount of ravulizumab in the blood of patients taking subcutaneous ravulizumab was no less than in patients taking intravenous ravulizumab and was maintained over 1 year of treatment. Efficacy measures (how well it works) remained stable in patients taking subcutaneous ravulizumab for 1 year and side effects were comparable with those of intravenous ravulizumab. Patients reported more satisfaction with subcutaneous ravulizumab than intravenous eculizumab, as assessed by the Treatment Administration Satisfaction Questionnaire. This study showed that patients with PNH can switch from intravenous eculizumab or ravulizumab to subcutaneous ravulizumab without loss of efficacy. Subcutaneous ravulizumab provides an additional treatment choice for patients with PNH.

Turkey real-life data: demographic features, treatment results and effects of comorbidities in chronic myeloid leukemia.

Aim: This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Materials & methods: Hospital records between 2005 and 2018 were retrospectively reviewed. Results: Of 861 CP-CML patients included, 31% had at least one comorbidity at diagnosis. Sex, cardiovascular disease status at diagnosis and molecular (at least major) and cytogenetic (partial and complete) responses were the independent predictors of survival. Conclusion: The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

This study aimed to identify patient characteristics, treatment patterns and outcomes and to evaluate the effects of presence of comorbidities at diagnosis in chronic phase (CP)-chronic myeloid leukemia (CML) patients in Turkey. Hospital records of patients between 2005 and 2018 were retrospectively reviewed. Of the included 861 CP-CML patients, 31% had at least one comorbidity at diagnosis. The survival of the patients was affected by sex, cardiovascular disease status at diagnosis, and molecular (at least major) and cytogenetic (partial and complete) responses. The response rates of CP-CML patients to the tyrosine kinase inhibitors were satisfactory. In addition to tolerability and side effect profiles of drugs, comorbidity status of patients should also be considered in treatment choice in CML patients.

Gene therapy in haemophilia: literature review and regional perspectives for Turkey.

Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.

The value of ultrasonography in detecting early arthropathic changes and contribution to the clinical approach in patients of hemophilia.

PURPOSE\AIM: Hemophilia affects the blood clotting process, is a genetic disease characterized by recurrent bleeding. The hemophilia early arthropathy detection with ultrasound (HEAD-US) procedure and scoring method were designed for the detection of early changes in affected joints of patients. In this article, it was aimed to detect early arthropathic changes in the joints of hemophilia patients with the HEAD US scoring system and to investigate its clinical contribution. It was aimed to investigate the effectiveness of HEAD-US scoring in showing early joint damage in subclinical hemophilia cases and its contribution to treatment. METHODS: The present study included 50 hemophilia patients who were admitted to Departments of Pediatric and Adult Hematology for routine follow-up. During routine follow-up controls, patients were scored by physical examination and HJHS 2.1 and by ultrasonography and HEAD US. Statistical tests were used to analyze joint health status and the results of US examination in the patient group. RESULTS: A total of 294 joints (elbow n = 100, knee n = 94, ankle n = 100) were evaluated by ultrasonography. The mean HJHS and HEAD-US scores of the patients were 14.94 ± 15.18 and 15.6 ± 12.6, respectively. CONCLUSIONS: HEAD-US is accepted to be more sensitive than HJHS in detecting early signs of arthropathy. Detection of early abnormalities by ultrasonography will enable the development of individualized treatment protocols and to the prevention of arthropathy development.

Comparative expression analysis of dasatinib and ponatinib-regulated lncRNAs in chronic myeloid leukemia and their network analysis.

LncRNAs are associated with malignancies with their tumor suppressor/oncogenic properties. Although many studies are conducted related to the mechanism of action for dasatinib and ponatinib in chronic myeloid leukemia (CML), their comparative effects on lncRNA expressions are largely unknown. Hence, we aimed to define the lncRNAs involved in the treatment of CML with dasatinib and ponatinib. We measured the cytotoxicities of dasatinib/ponatinib with CCK-8 assay and identified differentially expressed lncRNAs (DEL) by qRT-PCR. We determined the principal functions of DELs by Ingenuity Pathway Analysis (IPA) and performed gene ontology (GO) analysis for apoptosis and anti-proliferation-related lncRNAs. Apoptotic and anti-proliferative activities of dasatinib/ponatinib were confirmed by flow-cytometry. In K562 cells, dasatinib/ponatinib re-regulated lncRNAs which were dysregulated in leukemia. DELs after treatment (forty with dasatinib, thirty-seven with ponatinib) were related to increased cell death; decreased cell viability, proliferation, tumor growth, invasion, migration. Dasatinib-mediated network was related to cancer, hematological disease while ponatinib-mediated network was associated with cancer, cell death/survival, cell-to-cell signaling/interaction. Both treatments predicted activation of IFNγ, IL1ß, TNF as upstream regulators, specially this effect was higher in dasatinib. Comparison analysis showed that ponatinib was predicted more effective in cell death of tumor cell line than dasatinib. We confirmed that ponatinib was more potent than dasatinib to induce apoptosis and inhibit proliferation of CML cells, in consensus with IPA and GO analysis results. LncRNAs are specifically involved in anti-leukemic activities of dasatinib and ponatinib. Our findings will contribute to understanding signalization occurring in CML cells after standard treatments.

Results of multicenter registry for patients with inherited factor VII deficiency in Turkey.

INTRODUCTION: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients. METHODS: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded. RESULTS: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%). CONCLUSION: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required.

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.

Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia: A Multicenter Turkish Experience

Objective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without. Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed. Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs). Conclusion: Allogeneic HCT with MSDs or MUDs is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.

The Effect of Cryotherapy on the Prevention of Oral Mucositis and on the Oral pH Value in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of cryotherapy on the prevention of oral mucositis (OM) and on the oral pH value in patients with multiple myeloma undergoing autologous stem cell transplantation. DATA SOURCES: This nonrandomized controlled clinical trial was carried out in Bone Marrow Transplant Centers of three hospitals with total 32 patients. In addition to standard oral care, a total of 80 minutes of cryotherapy was applied to the experimental group. OM was assessed according to the World Health Organization's Oral Toxicity Scale before chemotherapy and for 21 days after chemotherapy (every day in the first 14 days, then every other day until the 21st day [if not discharged]). CONCLUSION: According to the findings, cryotherapy did not change the incidence of oral OM, and neither affected the severity of nor decreased the duration of it. Oral pH value was found to be significantly different between the patient groups only before and 1 day after chemotherapy. IMPLICATIONS FOR NURSING PRACTICE: Cryotherapy is an inexpensive, easy-to-use method with no side effects; it would be beneficial to continue cryotherapy to prevent the development of OM in patients with cancer receiving drugs with a short half-life such as melphalan. It is also recommended to conduct further studies with different chemotherapy drugs with short half-lives to determine its effect on the prevention of OM development.