Eltrombopag treatment in thrombocytopenia following hematopoietic stem cell transplantation: A multicenter real-world experience.

INTRODUCTION: Thrombocytopenia is among the most common complications following hematopoietic stem cell transplantation and is associated with increased mortality and morbidity with no standard treatment yet. In this multicenter and retrospective study, we aim to present our multi-center experience of Eltrombopag treatment in patients with isolated thrombocytopenia following HSCT. MATERIAL-METHOD: A total of 73 patients from 5 centers who underwent autologous or allogeneic stem cell transplantation, had no primary disease relapse, all of whom had neutrophil engraftment, complete chimerism, and who were diagnosed with Prolonged Isolated Thrombocytopenia (PIT) or Secondary Failure Of Platelet Recovery (SFPR) were included in the study. The patients were initiated on Eltrombopag at a dose of 50-150 mg. Complete response was defined as a platelet count >50×109/L for 7 consecutive days with no transfusion support. RESULTS: A total of 50.3% of the patients underwent Autologous and 49.7% Allogeneic Stem Cell Transplantation, 54.8% were diagnosed with PIT, and 45.2% were diagnosed with SFPR, and the treatment with 50-150 mg/day Eltrombopag was initiated on the median day +42. Complete response was achieved in 71.2% of these patients on the median day 23 of the treatment. No significant effects of the initial dose (50-150 mg/day) were detected in the Complete Response in the multivariate analysis on response. An insufficient number of Megakaryocytes in the bone marrow before Eltrombopag treatment was determined as an independent risk factor in determining the response (OR 3.57, 95% CI 1.21-10.55). The overall survival of the patients who did not respond to Eltrombopag was found to be significantly worse than that of patients who responded (p=0.022, HR:2.74, 95% CI 1.12-6.54). CONCLUSION: As a result of the present study, Eltrombopag treatment was found to be effective and safe in thrombocytopenia that develops following hematopoietic stem cell transplantation. It was concluded that its use may be more effective in patients with sufficient bone marrow megakaryocytes before the treatment and an initial dose of 50 mg/day may be appropriate in terms of cost, effectiveness, and toxicity. Large-scale randomized and controlled prospective studies are needed to determine the roles of Eltrombopag treatment in patients with post-transplant PIT and SFPR.

Comparison of Infectious Complications in Patients Receiving High-Dose Cyclophosphamide as GvHD Prophylaxis After Transplantation From A 9/10 HLA-Matched Unrelated Donor with Standard GvHD Prophylaxis After Transplant From A Fully Matched Related Donor.

Background: The aim of this study was to evaluate whether cyclophosphamide administered after allogeneic stem cell transplantation (ASCT) from 9/10 HLA-Matched Unrelated Donors (MMUD) increases the rates of bacterial, fungal, viral infections, complications (hemorrhagic cystitis (HC)), and infection-related mortality compared to allogeneic stem cell transplantation from matched related donors (MRD). Methods: This is a retrospective multicenter study. 45 MMUD ASCT patients who received posttransplant cyclophosphamide+methotrexate+calcineurin inhibitor compared with 45 MRD ASCT patients who received methotrexate+calcineurin inhibitor. Results: Although there was a statistically significant prolongation of neutrophil engraftment time in the PTCy arm, there was no statistically significant difference in bacterial infection frequencies between the groups (PTCy; 9 (20%), control; 8 (17.8%), p=0.778). The distribution of CMV infection in the first 100 days was similar (p=0.827), but the distribution of CMV infection rate between the 100th and 365th days was observed more frequently in the control group (p=0.005). HC rates and their grades were similar in both groups (PTCy; 4 (8.8%), control; 6 (13.3%) p=0.502). The rates of VZV infection and invasive aspergillosis were similar in the PTCy and control groups (13.3% in the PTCy and 17.8% in the control group p=0.561). There is also no statistically significant difference in survival analysis (OS, LFS, GRFS, RI, IRM, NRM) between groups. However, the incidence of cGVHD was significantly higher in the control group (P=0.035). Conclusions: The addition of PTCy to standard GvHD prophylaxis in MMUD ASCT does not lead to an increase in CMV reactivation, bacterial infections, invasive fungal infection, viral hemorrhagic cystitis, or mortality.

Gilteritinib (XOSPATA®) in Turkey: Early Access Program Results.

Background And Objectives: Gilteritinib (XOSPATA®, Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor, involved in both c-Kit and FMS-like tyrosine kinase 3 (FLT3) resistance. In the phase 3 ADMIRAL trial, gilteritinib was compared with the standard of care in (R/R) acute myeloid leukemia (AML) patients who harbored any FLT3 mutation and showed superior efficacy with regard to response and survival. Objectives: This research aimed to investigate the real-life efficacy and safety of gilteritinib in FLT3-positive R/R AML patients who were treated as a part of an early access program held in Turkey in April 2020 (NCT03409081). Results: The research included 17 R/R AML patients who had received gilteritinib from seven centers. The overall response rate was 100%. The most common adverse events were anemia and hypokalemia (7 patients, 41.2%). Grade 4 thrombocytopenia was observed in one patient only (5.9%), leading to permanent treatment discontinuation. Patients with peripheral edema had a 10.47 (95% CI: 1.64-66.82) times higher risk of death than those without peripheral edema (p<0.05). Conclusion: This research showed that patients with febrile neutropenia and peripheral edema were at a high risk of death when compared to patients without febrile neutropenia and peripheral edema.

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.

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.

Extramedullary Relapse in a CML Patient after Allogeneic Stem Cell Transplantation.

Myeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature granulocytic cells. It is a rare entity during the course of CML patients especially after allogeneic stem cell transplantation (SCT). Relapse without bone marrow involvement is much rarer. We report a case of CML patient who relapsed with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was performed because of refractory disease to tyrosine kinase inhibitors. Complete cytogenetic and molecular response was achieved after allogeneic SCT followed by dasatinib treatment. Approximately 5 years after the transplantation, very rapidly progressive lesion was documented and diagnosed as GS although he was at molecular and cytogenetic remission. The patient died during chemotherapy due to sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML patients with molecular and cytogenetic remission. Since it is a very aggressive disease with a poor prognosis, combined chemoradiotherapies with other possible options like DLI or second allogeneic SCT should be considered as soon as the diagnosis is confirmed.

Determining expression of miRNAs that potentially regulate STAT5A and 5B in dasatinib-sensitive K562 cells.

In the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down- and upregulation of the miRNAs were compared using the ΔΔCT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.

Multicenter Retrospective Analysis of Turkish Patients with Chronic Myeloproliferative Neoplasms.

OBJECTIVE: Chronic myeloproliferative neoplasms (CMPNs) that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are Philadelphia-negative malignancies characterized by a clonal proliferation of one or several lineages. The aim of this report was to determine the demographic features, disease characteristics, treatment strategies, and survival rates of patients with CMPNs in Turkey. MATERIALS AND METHODS: Across all of Turkey, 9 centers were enrolled in the study. We retrospectively evaluated 708 CMPN patients' results including 390 with ET, 213 with PV, and 105 with PMF. RESULTS: The JAK2V617F mutation was found positive in 86% of patients with PV, in 51.5% of patients with ET, and in 50.4% of patients with PMF. Thrombosis and bleeding at diagnosis occurred in 20.6% and 7.5% of PV patients, 15.1% and 9% of ET patients, and 9.5% and 10.4% of PMF patients, respectively. Six hundred and eight patients (85.9%) received cytoreductive therapy. The most commonly used drug was hydroxyurea (89.6%). Leukemic and fibrotic transformations occurred at rates of 0.6% and 13.2%. The estimated overall survival in PV, ET, and PMF patients was 89.7%, 85%, and 82.5% at 10 years, respectively. There were no significant differences between survival in ET, PV, and PMF patients at 10 years. CONCLUSION: Our patients' results are generally compatible with the literature findings, except for the relatively high survival rate in PMF patients. Hydroxyurea was the most commonly used cytoreductive therapy. Our study reflects the demographic features, patient characteristics, treatments, and survival rates of Turkish CMPN patients.

Formación de derrame pleural en el curso de un mieloma / Pleural effusion formation in the course of myeloma

No disponible

18F-FDG and 18F-NaF PET/CT Findings of a Multiple Myeloma Patient With Thyroid Cartilage Involvement.

Thyroid cartilage is a very rare extramedullary involvement location in multiple myeloma. We present both F-NaF and F-FDG PET/CT findings of a multiple myeloma patient with thyroid cartilage involvement. In this patient, increased FDG and more intensely increased NaF uptake were seen on thyroid cartilage. In addition, some bone lesions had more intense NaF than FDG uptake, and some were only NaF avid. Although F-FDG PET/CT has an important role in plasma cell neoplasms, we considered that F-NaF PET/CT is also very useful to detect small lytic lesions that might be overlooked on F-FDG PET/CT.

Relationships between plasma pentraxin 3 levels and inflammation markers patients with tunneled permanent catheter in hemodialysis.

PURPOSE: Vascular access (VA) devices may contribute to chronic inflammation in hemodialysis (HD). Pentraxin 3 (PTX3) is a recently discovered acute phase protein that responds more rapidly than other inflammatory markers. This study compared PTX3 and other markers between HD patients and healthy controls. METHODS: The study population included 30 patients with tunneled permanent catheter (TPC), 30 patients with arteriovenous fistula (AVF) and 30 healthy controls. Hemogram, biochemical assays, ferritin, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and PTX3 were evaluated in all groups. RESULTS: PTX levels were highest in HD patients with TPC, intermediated in HD patients with AVF and lowest in healthy controls (5.2 + 2.4 vs. 3.1 + 1.3 vs. 1.8 + 0.7, p<0.001 for all comparisons). PTX3 levels correlated strongly to hs-CRP (r = 0.857) and moderately to TNF-α, NLR, ferritin and total neutrophil count. PTX3 and albumin levels had a negative correlation. PTX3 levels were higher in patients with 8 months of TPC than those with 7 months or less. CONCLUSIONS: PTX3 levels are significantly elevated in all patients on HD, but presence and extended duration of TPC are associated with incrementally higher levels of PTX3 and other inflammatory markers. PTX3 and NLR may be useful in assessing chronic inflammatory states in HD.

Seasonal Association of Immune Thrombocytopenia in Adults.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. AIMS: We investigated whether months and/or seasons have triggering roles in adults with ITP. STUDY DESIGN: Descriptive study. METHODS: A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. RESULTS: The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). CONCLUSION: This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching maximum levels in the spring in places where a Mediterranean climate is seen.

Bortezomib induces apoptosis by interacting with JAK/STAT pathway in K562 leukemic cells.

In the current study, we aimed to identify the cytotoxic and apoptotic effects of bortezomib (BOR) on human K562 chronic myelogenous leukemia cells and to evaluate the potential roles of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway members STAT3, STAT5, and JAK2 on BOR-induced cell death of leukemic cells. Cell viability was assessed via trypan blue dye exclusion test, and cytotoxicity of the BOR-treated cells was conducted by 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-carboxanilide inner salt (XTT) assay. The relative messenger RNA (mRNA) expression levels of STAT3, STAT5A, STAT5B, and JAK2 were analyzed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). On the other hand, their protein expression levels were detected by western blot method. The obtained results indicated that BOR treatment reduced cell viability and induced leukemic cell apoptosis in a dose- and time-dependent manner as compared to untreated control cells. While mRNA expression levels of STAT5A, STAT5B, and STAT3 were significantly reduced following BOR treatment when compared to untreated controls, it had no effect upon JAK2 mRNA expression. As for protein levels, STAT expressions were downregulated after BOR treatment especially at 72nd and 96th hours. Our results pointed out that BOR treatment had a significant potential of being an anticancer agent for chronic myelogenous leukemia therapy, and this effect could be due to the expressional downregulations of JAK/STAT pathway members.

Changes in molecular biology of chronic myeloid leukemia in tyrosine kinase inhibitor era.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by a reciprocal translocation between long arms of chromosomes 9 and 22 t(9;22) that generates the BCR-ABL fusion gene. If left untreated, newly diagnosed chronic phase CML patients finally progress to accelerated and blastic phase. After the introduction of tyrosine kinase inhibitors (TKIs), treatment strategies of CML changed dramatically. However, the development of resistance to TKIs started to create problems over time. In this review, the current information about CML biology before and after imatinib mesylate treatment is summarized.

Significant independent predictors of vitamin d deficiency in inpatients and outpatients of a nephrology unit.

Aims. Kidney disease was found to be a major risk factor for vitamin D deficiency in a population study of patients hospitalized. The aims of the study were to describe the prevalence of vitamin D deficiency inpatients and outpatients in a nephrology department during fall and to evaluate effect of assessing serum 25-hydroxyvitamin D (25(OH)D) levels and previous supplementation of cholecalciferol on vitamin D status. Methods. We studied 280 subjects in total, between October and January. The subjects were recruited from the following two groups: (a) inpatients and (b) outpatients in nephrology unit. We examined previous documentary evidence of vitamin D supplementation of the patients. Results. The prevalence of vitamin D deficiency among these 280 patients was 62,1% (174 patients). Fifty-three patients (18.9%) had severe vitamin D deficiency, 121 patients (43.2%) moderate vitamin D deficiency, and 66 patients (23.6%) vitamin D insufficiency. In logistic regression analysis female gender, not having vitamin D supplementation history, low serum albumin, and low blood urea nitrogen levels were significant independent predictors of vitamin D deficiency while no association of vitamin D deficiency with diabetes mellitus, serum creatinine, eGFR, and being hospitalized was found. Conclusion. Vitamin D deficiency, seems to be an important problem in both inpatients and outpatients of nephrology. Monitoring serum 25(OH)D concentrations regularly and replacement of vitamin D are important. Women in Turkey are at more risk of deficiency and may therefore need to consume higher doses of vitamin D.

Serum fetuin-A levels, QT dispersion and P dispersion in dialysis patients.

BACKGROUND: This study aims to find association of fetuin-A with serum lipids, QT dispersion (QT-d), and P dispersion (P-d) in dialysis patients. METHODS: Fetuin-A serum levels were assessed in 50 dialysis patients. RESULTS: Serum fetuin-A levels were significantly associated with QT-d (r = 0.289, p = 0.044), P-d (r = 0.39, p = 0.005), total cholesterol (r = 0.526, p = 0.000), low-density lipoprotein cholesterol (LDL-C) (r = 0.456, p = 0.00), triglyceride (r = 0.360, p = 0.011) and highly sensitive C-reactive protein (hsCRP) (r = -0.347, p = 0.030). In step-wise multiple regression analysis including being on hemodialysis (HD), presence of diabetes mellitus (DM), total cholesterol, LDL-C, triglycerides, hsCRP, only total cholesterol (b = 0.419, p = 0.03), and hsCRP (b = -0.316, p = 0.03) proved to be independent predictors of serum fetuin-A levels. QT-d showed a linear correlation with total cholesterol (r = 0.309, p = 0.029), LDL-C (r = 0.304, p = 0.038), P-d (r = 0.390, p = 0.005), and fetuin-A levels (r = 0.289, p = 0.044). In multiple regression analyses, the independent predictor of QT-d was being on HD (b = -0.417, p = 0.004), whereas total cholesterol, LDL-C, presence of DM, serum fetuin-A levels, and P-d had no independent effect on corrected QT (QT-C). Being on HD and age were important determinants of P-d whereas presence of DM, total cholesterol, LDL-C, fetuin-A, and QT-d had no independent effect on P-d. CONCLUSIONS: Lower fetuin-A levels are associated with high hsCRP and low cholesterol levels in dialysis patients.

Quality of life and supportive care in multiple myeloma.

UNLABELLED: Multiple myeloma is the second most common haematological malignancy. Novel therapies have led to improvement in survival. Current myeloma management is matching the progress made in improved survival through disease control while optimising quality of life with effective supportive care. Supportive treatment is an essential part of the therapeutic management of myeloma patients because it is directed towards improving the patient's quality of life and also can improve survival. The aim of this review is to highlight the relationship among life of quality, supportive care, and improvement in survival. CONFLICT OF INTEREST: None declared.

Turkish Chronic Myeloid Leukemia Study: Retrospective Sectional Analysis of CML Patients.

OBJECTIVE: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices. MATERIALS AND METHODS: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs. RESULTS: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment. CONCLUSION: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care. CONFLICT OF INTEREST: None declared.