Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. METHODS: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. RESULTS: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). CONCLUSIONS: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment.

Frontline nilotinib treatment in Turkish patients with Philadelphia chromosome-positive chronic Myeloid Leukemia in chronic phase: updated results with 2 years of follow-up.

OBJECTIVES: This report presents final results (24 months of follow-up) from the first prospective, national study of frontline nilotinib in chronic myeloid leukemia (CML) patients in Turkey. METHODS: Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N = 112) received nilotinib 300 mg twice daily. The primary endpoint, which was the cumulative rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months, was previously reported (66.1% [80% CI, 59.7%-72.0%]). ClinicalTrials.gov identifier NCT01274351 Results: By 24 months, 83.0% of patients achieved MMR, and 50.9% achieved MR4.5 (BCR-ABL1IS ≤0.0032%). Safety results at 24 months were consistent with those at 12 months. No additional deaths or disease progressions to accelerated phase/blast crisis were observed between 12 and 24 months. DISCUSSION: Treatment with nilotinib 300 mg twice daily for 2 years provided high MMR with a good safety/tolerability profile in newly diagnosed CML-CP patients in Turkey. Assessment of MMR across time points showed increasing rates through 18 months, after which as lower rate of increase was observed. The safety profile of nilotinib 300 mg twice daily with 24 months of follow-up was similar to that observed at 12 months, and no new safety concerns were identified. These efficacy and safety findings are consistent with the results from the 12-month analysis of this study and from previous nilotinib studies. These findings support nilotinib as an option for frontline treatment of CML-CP. CONCLUSION: Frontline nilotinib treatment provided sustained efficacy, with good tolerability, over 24 months in newly diagnosed CML-CP patients.

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

OBJECTIVES: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months. METHODS: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. This study is registered with ClinicalTrials.gov (NCT01274351). RESULTS: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1IS ≤0.0032%) by 12 months. During the first year of treatment, one patient progressed to blast crisis and two patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. CONCLUSION: These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP with low and intermediate risk.

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.

OBJECTIVE: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1(IS)]) by 12 months. METHODS: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. RESULTS AND CONCLUSIONS: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR(4.5) (BCR-ABL1(IS) ≤ 0.0032%) by 12 months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP.

Comparison of Rotational Thromboelastography Findings in Pseudoexfoliation Syndrome Patients and Healthy Controls.

PURPOSE: Rotational thromboelastography (ROTEM) is a useful test for studying the characteristics of fibrin clot formation. As patients with pseudoexfoliation (PEX) have an increased risk for thrombotic events, clot-forming dysfunction may play a role. The aim of this study is to compare ROTEM findings in PEX syndrome patients with age-matched and sex-matched healthy controls. PATIENTS AND METHODS: A total of 21 patients with PEX syndrome and 22 age-matched and sex-matched healthy controls were included. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer. RESULTS: The mean age of patients with PEX and controls was 66.5±8.3 and 65.9±9.5 years, respectively (P=0.7). The 2 groups did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, PEX patients showed a significantly decreased clotting time when compared with healthy controls (79.8 vs. 98.0 s; P=0.01), indicating faster clot formation. Other ROTEM parameters did now show any difference between the 2 groups. CONCLUSIONS: PEX patients showed faster clotting time when compared with healthy controls. This fibrin clot formation dysfunction may lead to vascular thrombotic events in these patients. Further studies are needed to elucidate the exact underlying mechanism of thrombosis seen in PEX patients.

Potential of polymerase chain reaction and galactomannan for the diagnosis of invasive aspergillosis in patients with febrile neutropenia.

The incidence of invasive aspergillosis (IA) has increased over the last years, especially in immuncompromised patients with high mortality rates. Because of difficulties about the diagnosis; serological methods [galactomannan (GM) antigen test] and polymerase chain reaction (PCR) developed in recent years. MycAssay Aspergillus PCR performance in the diagnosis of IA was evaluated and compared with the GM and in-house PCR. This study was conducted with 358 serum samples obtained from 99 patient with febrile neutropenic episodes who were followed in haematology and bone marrow transplantation units. Patients were classified by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 18 of them is proven and probable IA. GM antigen test and two different real-time PCR; one of them is fist commercial PCR for IA; Mycassay Aspergillus and the other one is in-house real-time PCR performed. Sensitivity values were Mycassay Aspergillus PCR, in-house PCR, and GM 65.38%, 11.53% and 23.07%, respectively. The high sensitivity obtained from Mycassay Aspergillus PCR and sensitivity is increased by using a combination of diagnostic methods. GM antigen test and real-time PCR could be beneficial for early diagnosis and treatment of IA. For routine usage of PCR as diagnostic assay more studies needed in future.

Whole blood gene expression analyses in patients with single versus recurrent venous thromboembolism.

INTRODUCTION: Venous thromboembolism may recur in up to 30% of patients with a spontaneous venous thromboembolism after a standard course of anticoagulation. Identification of patients at risk for recurrent venous thromboembolism would facilitate decisions concerning the duration of anticoagulant therapy. OBJECTIVES: In this exploratory study, we investigated whether whole blood gene expression data could distinguish subjects with single venous thromboembolism from subjects with recurrent venous thromboembolism. METHODS: 40 adults with venous thromboembolism (23 with single event and 17 with recurrent events) on warfarin were recruited. Individuals with antiphospholipid syndrome or cancer were excluded. Plasma and serum samples were collected for biomarker testing, and PAXgene tubes were used to collect whole blood RNA samples. RESULTS: D-dimer levels were significantly higher in patients with recurrent venous thromboembolism, but P-selectin and thrombin-antithrombin complex levels were similar in the two groups. Comparison of gene expression data from the two groups provided us with a 50 gene probe model that distinguished these two groups with good receiver operating curve characteristics (AUC 0.75). This model includes genes involved in mRNA splicing and platelet aggregation. Pathway analysis between subjects with single and recurrent venous thromboembolism revealed that the Akt pathway was up-regulated in the recurrent venous thromboembolism group compared to the single venous thromboembolism group. CONCLUSIONS: In this exploratory study, gene expression profiles of whole blood appear to be a useful strategy to distinguish subjects with single venous thromboembolism from those with recurrent venous thromboembolism. Prospective studies with additional patients are needed to validate these results.

Candida norvegensis fungaemia in a neutropenic patient with acute non-lymphoblastic leukaemia.

We report a case of fungaemia resulting from Candida norvegensis in a patient with acute non-lymphoblastic leukaemia-M4 from Turkey. Candida norvegensis was isolated from two different peripheral blood samples that were taken at 2-day intervals. Despite treatment with liposomal amphotericin B, the patient died of multi-organ system failure.