Browsing by Author "Elezović, Ivo (12782840600)"

Historically in hemophilia, outcome measures have not been collected systematically. Hence, there are insufficient clearly defined, evidence-based measures that can be applied consistently across hemophilia trials. This review focuses on some key challenges to evaluating patient outcomes and performing trials identified by experts at the Fourth and Fifth Zurich Haemophilia Forums. As procedures appear inconsistent across Europe, guidelines require modification to be more appropriate and/or realistically achievable. The outcome measures utilized, and the timing of their collection, should also be standardized, and more objective measures used where feasible. Implementation of outcome measures could be refined through greater understanding of patient heterogeneity, and tailored to differentiate between hemophiliaand aging-related disease effects. Furthermore, robust outcome measures that can also inform healtheconomic decisions are increasingly needed. Lastly, as patient recruitment poses a challenge, the panel proposed a call for action to motivate physicians and patients to participate in clinical trials. © W. S. Maney & Son Ltd 2012.

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans- retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 109/1 at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 109/1 received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 109/1) than in the group of patients receiving ATRA and chemotherapy (14.0 x 109/1). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3+7' chemotherapy (DNR 45 mg m-2,1-3 days, ARA-C 200 mg m-2, 1-7 days) followed by two courses of standard '2+5' chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).

Between February 1992 and November 1996 we treated 30 newly diagnosed acute promyelocytic leukaemia (APL) patients either with oral all-trans- retinoic acid (ATRA) alone (45 mg m-2) or with a simultaneous combination of ATRA (45 mg m-2), daunorubicin (DNR, 50 mg/m-2 for 3 days) and cytosine arabinoside (ARA-C, 200 mg m-2 for 7 days). There were 15 patients in each group. Patients with a white blood cell count < 5 x 109/1 at diagnosis received only ATRA as an induction therapy. Patients with initial white blood cell count > 5 x 109/1 received a combination of ATRA, DNR and ARA-C as an induction therapy. Within the first 20 days of induction, there were two early deaths in the group of patients receiving only ATRA, and six early deaths in the group of patients treated with a combination of ATRA and chemotherapy. Ten out of 13 patients (76.9%) receiving ATRA only achieved complete remission (CR) whereas seven out of nine patients (77.8%) receiving ATRA with chemotherapy achieved CR. Initial median peripheral white blood cell counts were significantly lower in the group of patients treated with ATRA alone (2.3 x 109/1) than in the group of patients receiving ATRA and chemotherapy (14.0 x 109/1). Morphological evidence of differentiation was noted in all patients entering CR. Patients in both groups who achieved CR received one course of standard '3+7' chemotherapy (DNR 45 mg m-2,1-3 days, ARA-C 200 mg m-2, 1-7 days) followed by two courses of standard '2+5' chemotherapy (DNR 50 mg m-2 1-2 days, ARA-C 200 mg m-2 1-5 days) as a consolidation therapy. Patients not achieving remission (three out of 13 in the ATRA group and two out of nine in ATRA+chemotherapy group) did not respond to salvage chemotherapy and all died within 3 months of diagnosis. Only one out of 10 patients (10%) in CR, treated with ATRA is in relapse after 18 months. In patients treated with ATRA alone two out of 10 (20%) survived 58 months following diagnosis whereas in the ATRA+chemotherapy group one out of seven has already survived their 58th month since diagnosis. Four out of eight patients with an early death died of retinoic acid syndrome. Other toxicities due to ATRA were minimal (cheilitis, xerosis, dermatitis, diarrhoea, liver damage or pseudotumor cerebri).

Introduction Therapy related acute myeloid leukaemia (t-AML) is a distinct clinical entity recognized by the World Health Organization classification occurring after chemotherapy and/or radiation treatment administered for a previous disease. T-AML is characterised by pancytopenia, three-lineage myelodysplasia, high frequency of unfavourable cytogenetics and short survival. Objective The aim of this study was to analyse clinical, cytogenetic, and cytological characteristics of t-AML and their impact on survival. Methods Seventeen patients with t-AML (8 male and 9 female; median age 59 years) were identified among 730 consecutive patients with acute myeloid leukaemia. The degree of three-lineage dysplasia as well as haematological, cytological and cytogenetic analyses, were assessed by standard methods. Results The patients survived a median of 62.5 days with the 10% probability of survival during two years. Prognostically favourable factors were a higher percentage of dysplastic granulocytic cells, age less than 60 years, and presence of prognostically favourable karyotype inv(16), t(15;17), t(8;21). Conclusion The stated prognostic factors that include age, cytogenetics findings and granulocytic dysplasia analysis could contribute to adequate risk stratification of t-AML, though fuller results would require additional analyses.

For hemophilia patients with inhibitors, immune tolerance induction (ITI) may help to restore clinical response to factor (F) VIII or FIX concentrates. Several ITI regimens and protocols exist; however, despite 30yr of progressive investigation, the ITI evidence base relies mainly on observational data. Expert opinion, experience, and interpretation of the available evidence are therefore valuable to support clinical decision-making. At the Sixth Zürich Haemophilia Forum, an expert panel considered recent data and consensus to distill key practice points relating to ITI. The panel supported current recommendations that, where feasible, ITI should be offered early to children and adults (ideally ≤5yr of inhibitor detection) when inhibitor titers are <10 Bethesda units (BU) and should be stopped when successful tolerance is achieved. For hemophilia A inhibitor patients, ITI can be founded on recombinant FVIII at high doses. The panel considered that patients with a high bleeding frequency should be offered additional prophylaxis with a bypassing agent. For patients with hemophilia B, there may be a benefit of genetic testing to indicate the risk for inhibitors. ITI is often less effective and associated with a greater risk of side effects in these patients. For high-titer inhibitor (≥5BU) hemophilia B patients, the panel advised that bypassing agents could be offered on demand in addition to ITI. Within future ITI regimens, there may be a role for additional immunosuppressant therapies. Participants agreed that research is needed to find alternatives to ITI therapy that offer durable and sustained effects and reduced rates of complications. © 2012 John Wiley & Sons A/S.

Introduction Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder characterized by giant platelets thrombocytopenia, prolonged bleeding time, frequent hemorrhages with considerable morbidity. Data on the outcome of pregnancy and gynecological intervention in BSS are rare and there are no general therapeutic recommendations. Cases Outline We report two cases of BSS. In the first case a 29-year-old patient with BSS was admitted in 8 weeks of gestation. The diagnosis of BSS was made on the basis of prolonged bleeding time, giant-platelets thrombocytopenia, and absent ristocetin-induced platelet aggregation. In 38 week of gestation Cesarean section, with platelets transfusion preparation, was performed. Obstetric intervention passed without complication. Postoperative course was complicated with a three-week vaginal bleeding resistant to platelet transfusion. Neonate platelet count was normal. Our second case was a 28-year-old patient with BSS, hospitalized for ovarial tumor surgery. The patient was prepared for the intervention with platelets transfusion. The surgery was uncomplicated, but on the second postoperative day a massive vaginal bleeding, resistant to the platelet transfusion, developed. Bleeding control was achieved with activated recombinant factor VII. Twelve hours the patient developed later hypertensive crisis with epileptic seizure due to subarachnoid hemorrhage. Therapy was continued with platelet transfusion, antihypertensive and antiedema drugs. PH examination of tumor tissue showed hemorrhagic ovarial cyst. Conclusion Obstretic and gynecological intervention in women with BSS may be associated with a life-threatening bleeding thus requiring a multidisciplinary approach with adequate preparation. Because of the limited data in the literature, it is not possible to provide firm management recommendations and each case should be managed individually. © 2014, Serbia Medical Society. All rights reserved.

215 teeth were extracted in 62 haemophiliacs following a single infusion of factor VIII supplemented with antifibrinolytics. Tooth sockets were packed with Sorbacel gauze soaked with an antifibrinolytic. 1 group was sutured and the other left open. Primary closure of the extraction wound did not show direct effect on haemostasis. However, the size of the clot showed a statistically significant difference between the primary closure and open wound groups. The authors conclude that primary closure of the extraction wound protects the blood clot, makes the postoperative period more comfortable for patients and may subsequently decrease the risk of postoperative bleeding. © 1988 Munksgaard International Publishers Ltd.

215 teeth were extracted in 62 haemophiliacs following a single infusion of factor VIII supplemented with antifibrinolytics. Tooth sockets were packed with Sorbacel gauze soaked with an antifibrinolytic. 1 group was sutured and the other left open. Primary closure of the extraction wound did not show direct effect on haemostasis. However, the size of the clot showed a statistically significant difference between the primary closure and open wound groups. The authors conclude that primary closure of the extraction wound protects the blood clot, makes the postoperative period more comfortable for patients and may subsequently decrease the risk of postoperative bleeding. © 1988 Munksgaard International Publishers Ltd.

Owing to the heterogeneity in the clinical phenotype of haemophilia A and B, it is now recognized that disease severity (based on factor VIII/IX activity) may no longer be the most appropriate guide for treatment and that a 'one-size-fits-all' approach is unlikely to achieve optimal therapy. Based on the present literature and consensus views of a group of experts in the field, this article highlights key gaps in the understanding of the diverse relationships between bleeding phenotype and factors such as joint health, genetic susceptibility, laboratory parameters, quality of life and management of pain. Early prophylaxis is a potential 'gold standard' therapy and issues surrounding inhibitor development, variations in its clinical use and long-term outcomes are discussed. Comprehensive treatment should be individualized for all patients (including those with mild or moderate haemophilia and carriers). Wherever possible all patients should be given prophylaxis. However, adult patients with a milder haemophilia phenotype may be candidates for ceasing prophylaxis and switching to on-demand treatment. Regardless, all treatment (on-demand and prophylaxis) should be tailored towards both the patient's personal needs and their clinical profile. In addition, as the associations between risk factors (psychosocial, condition-related and treatment-related) and clinical features are unique to each patient, an individualized approach is required to enable patients to alter their behaviour in response to them. The practical methodologies needed to reach this goal of individualized haemophilia care, and the health economic implications of this strategy, are ongoing topics for discussion. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.