Ariella Tvito - Academia.edu (original) (raw)

Papers by Ariella Tvito

Thrombosis Research, Aug 1, 2017

To the editor: Acquired thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening t... more To the editor: Acquired thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening thrombotic microangiopathy resulting from autoantibodymediated inhibition of ADAMTS13 (ADisintegrin AndMetalloproteinase with a Thrombospondin type 1 motif, member 13), the key enzyme involved in the cleavage of ultra-large von Willebrand factor multimers [1]. Approximately 5–10% of TTP cases are encountered in the setting of pregnancy, with associated adverse maternal and fetal outcomes [1]. Herein we describe a case of acquired TTP in a pregnant patient and depict the role of anti-ADAMTS13 antibodies in the fetus.

$Research paper thumbnail of Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia in Adults$

Current Oncology Reports, May 21, 2016

Patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis ... more Patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have a dismal prognosis with less than 10 % of patients surviving 5 years. Most such patients cannot be rescued with currently available therapies, whatever the initial treatment they receive. Therefore, there is an urgent need for novel treatment options. Fortunately, over the past several years, an improved understanding of the biology of the disease has allowed the identification of rational molecular targets for therapeutic endeavors and the emergence of novel therapies has sparked great interest. This review will discuss the current treatment landscape for adult patients with relapsed and/or refractory ALL.

Orthopaedic Proceedings, Aug 1, 2008

Introduction: Currently patients who had undergone lower limb arthroplasty are discharged a few d... more Introduction: Currently patients who had undergone lower limb arthroplasty are discharged a few days after surgery, at which stage they still need anticoagulation treatment. The transition from hospital to the community is a sensitive period and is susceptible to mistakes and misunderstandings. Patients may underestimate the importance of the continuing treatment and their inconvenience to self-administrate subcutaneous treatment might decrease their compliance. The purpose of this prospective cohort study was to investigate the continuity of the treatment with subcutaneous low molecular weight heparin at the transition period from the hospital to the community. Materials and Methods: 209 consecutive consenting patients who had undergone lower limb arthroplasty were recruited. Ten were excluded from the study since they were subscribed oral anticoagulation; 4 patients developed pulmonary embolism and were not included, and 8 patients were lost to follow up. 187 patients were followed weekly by phone and were asked about their adherence to the daily treatment, about clinical signs suggesting a thromboembolic event and whether they sought medical assistance. Three months later there was another clinical follow up. Results: Of the 187 patients, 174 (93%; 95% CI 88.9% Discussion: The rate of compliance to anticoagulation treatment with subcutaneous low molecular weight heparin was encouraging. It demonstrates that the patients understand the necessity and importance of the treatment.

Frontiers in Immunology, Mar 29, 2023

Purpose: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment ... more Purpose: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient. Methods: A single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly. Results: Five XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was obtained for 111 (96%) of the treatments. Fifty-four IVIG preparations (49%) were harvested during the COVID-19 pandemic of which 76% Frontiers in Immunology frontiersin.org 01

Biologics: Targets & Therapy, Oct 1, 2021

The treatment of adults with ALL has undergone tremendous progress over the past 15 years. The ad... more The treatment of adults with ALL has undergone tremendous progress over the past 15 years. The advances have been particularly marked with B-lineage ALL. The development of bispecific antibodies directed against CD19 ushered in a new era in overcoming persistent minimal disease in newly diagnosed ALL patients as well as successfully treating those with relapsed disease. The immune-conjugates targeting CD22 have also had a similarly impressive role in improving the outcome in such patients. These advances are now being extended to frontline regimens for B-lineage ALL, including the Philadelphiachromosome-positive subtype. Over the past decade, the development of chimeric antigen receptor T-cell therapy (CAR-T) has ushered in a new era, opening up hope when none was available for patients with particularly advanced disease. Such advances come at a considerable price for toxicity, which, however, are lessening with experience and the development of new agents to ameliorate some of the toxicities. Unfortunately, the progress for T-cell in ALL has lagged behind that of B-lineage ALL. Of late, however, there are preliminary results of potentially exciting data using monoclonal antibodies against CD38, in the form of daratumumab, and it is hoped that these will lead to an equally successful advance in the treatment of TALL. Despite all these advances, ALL in adults remains a formidable disease. While ongoing progress is being made, also in the therapy of older patients, we are still lagging behind the almost totally curative potential of current therapy for childhood ALL.

Expert Opinion on Biological Therapy, Nov 1, 2017

ABSTRACT Introduction: Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects ab... more ABSTRACT Introduction: Acute lymphoblastic leukemia (ALL) is an uncommon disorder that affects about 20% of adults with acute leukemia. Historically, those who relapse from this condition have a dismal prognosis. Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. One recent development is the FDA approved therapy inotuzumab ozogamicin which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to possibly increase the number of patients who may achieve a state of minimal residual disease. Areas covered: In this review, the pre-clinical and clinical experiences with inotuzumab ozogamicin in lymphoma and ALL are reviewed. The article further includes the published phase I, II and III studies in ALL and considers the safety and efficacy of this treatment. Expert opinion: Inotuzumab ozogamicin is likely to be used, primarily, as a potent agent for relapsed ALL, either as the first choice or for those who fail treatment with blinatumumab. Its potential in newly diagnosed patients is currently unknown, such that the overall impact is likely to be important, but limited.

Supportive Care in Cancer, Mar 16, 2018

Purpose Bone loss-osteopenia and osteoporosis-is a recognized consequence of solid tumors in adul... more Purpose Bone loss-osteopenia and osteoporosis-is a recognized consequence of solid tumors in adults, of pediatric hematological malignancies, and of the treatment for these diseases, but little research has been published on the adverse effects of hematological malignancies on the bone in adults. The aim of this study is to identify hematological diseases that are associated with the highest prevalence and severity of osteoporosis. Methods We evaluated DXA (dual-energy X-ray absorptiometry) in a cross-section of 181 adult patients with hematological neoplasms, excluding multiple myeloma. All patients were over 18 years of age, signed a local institutional review board (IRB)approved consent form, and had completed a questionnaire regarding predisposing factors to osteoporosis. This data was supplemented by hospital charts. Results Bone loss as measured by DXA T scores was found in 65% of patients, of whom 38% had osteopenia and 27% osteoporosis. DXA Z scores under − 2.0 were found in 11.4% of patients, compared to the expected 2.5% of the normal population. The DXA Z scores varied by diagnosis, showing bone loss in 49% of chronic lymphocytic leukemia/small lymphocytic lymphoma, compared to 67% of non-Hodgkin lymphoma and 88% of Hodgkin disease; the scores were not affected by the duration of time from diagnosis to DXA (3.6, 2.0, and 1.6 years, respectively). Conclusion Adult patients with hematological malignancies have significant bone loss compared to a normal age-matched population. The type of diagnosis is more important than the time from diagnosis in predicting risk for bone loss. Recognition of bone loss in these patients may warrant prophylactic measures and lifestyle changes before, during, and after therapy.

Expert opinion on orphan drugs, Jan 13, 2017

Introduction: Despite uninterrupted efforts made to develop newer drugs and schedules in the trea... more Introduction: Despite uninterrupted efforts made to develop newer drugs and schedules in the treatment of acute myeloid leukemia (AML), the induction of chemotherapy with cytarabine and an anthracycline (the classical '7 + 3') still remains the standard of care. Unfortunately, many patients are not suitable for intensive induction therapy due to poor prognosis, age and comorbidities. For these challenging populations, the clinical outcome is poor and novel approaches are desperately required. One of these approaches is the liposomal formulation of drugs, allowing the delivery of more drug to the disease site and thereby improving efficacy and reducing toxicity. CPX-351 is a liposomal formulation of the cytotoxic drugs cytarabine and daunorubicin at synergistic concentrations. Area covered: In this article, we review the preclinical and clinical experience to date with CPX-351 for patients with AML. Phase I and II studies have been published and a randomized prospective phase III study has recently been completed and presented as an abstract. Expert opinion: CPX-351 is exclusively developed for use in AML. It is clearly active, as would be expected from its component makeup, and phase III data suggest that this may be the preferred initial combination therapy, at least for older patients with secondary AML.

Current Treatment Options in Oncology, Mar 1, 2017

Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No lo... more Opinion statementOver the past 15 years, the landscape of Ph+ ALL has changed dramatically. No longer the most dreaded form of acute leukemia, the advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era, as TKIs have become the backbone of any treatment regimen for Ph+ ALL. A greater number achieve a complete remission allowing for more patients to get the transplant, although probably less patients need a transplant. For the first time in decades, there is hope for older patients with Ph+ ALL. Defining residual disease at an increasingly lower level of disease burdens termed minimal residual disease (MRD) has allowed treatment algorithms to be designed based on deep molecular responses. The aggregate of recent data suggest that this is the most important endpoint to predict for long-term outcome and to decide on the optimal post-remission approach, including transplant. Novel agents, such as blinatumumab, are likely to be incorporated into therapy for relapse and as initial therapy in an attempt to increase the number of patients who may have deep molecular responses. Many more patients with Ph+ ALL are long-term survivors, and the future is looking brighter for this group of patients.

Internal and Emergency Medicine, Apr 22, 2023

Frontiers in Immunology

PurposePatients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment an... more PurposePatients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient.MethodsA single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly.ResultsFive XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was...

Clinical and Applied Thrombosis/Hemostasis

Introduction D-dimer is a small protein fragment produced during fibrinolysis. High D-dimer level... more Introduction D-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients. Nevertheless, data regarding D-dimer's prognostic impact among tertiary care intensive coronary care unit (ICCU) patients is scarce. Material and method All patients admitted to the ICCU between 1-12/2020 were prospectively included. Based on admission D-dimer level, patients were categorized into low and high D-dimer groups (< 500 ng/ml and ≥ 500 ng/ml) and also to age-adjusted D-dimer cutoff (500 ng/ml for ages ≤ 50 years old and age*10 for ages>50 years old). Results and discussion A total of 959 consecutive patients were included, including 296 (27.4%) and 663 (61.3%) patients with low and high D-Dimer levels, respectively. Patients with high D-dimer level were older compared with patients with low D-dimer level (age 70.4 ± 15 and 59 ± 13 years, p = 0.004) and had more comorbidities. The most common primary ...

The New England Journal of Medicine, Feb 7, 2019

The Devil Is in the Details A 75-year-old woman was admitted to the hospital with a 4-month histo... more The Devil Is in the Details A 75-year-old woman was admitted to the hospital with a 4-month history of weight loss (total weight loss, 8 kg) and night sweats. She reported no fever, arthralgias, co...

Journal of Clinical Medicine, 2021

Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine p... more Hypoxemia is a hallmark of coronavirus disease 2019 (COVID-19) severity. We sought to determine predictors of hypoxemia and related adverse outcomes among patients hospitalized with COVID-19 in the two largest hospitals in Jerusalem, Israel, from 9 March through 16 July 2020. Patients were categorized as those who developed reduced (<94%) vs. preserved (≥94%) arterial oxygen saturation (SpO2) within the first 48 h after arrival to the emergency department. Overall, 492 hospitalized patients with COVID-19 were retrospectively analyzed. Patients with reduced SpO2 were significantly older, had more comorbidities, higher body surface area (BSA) and body mass index (BMI), lower lymphocyte counts, impaired renal function, and elevated liver enzymes, c-reactive protein (CRP), and D-dimer levels as compared to those with preserved SpO2. In the multivariable regression analysis, older age (odds ratio (OR) 1.02 per year, p < 0.001), higher BSA (OR 1.16 per 0.10 m2, p = 0.003) or BMI (OR...

International Journal of Laboratory Hematology

Patients with COVID-19 are at increased risk of thromboembolism. In a recent study of 184 patient... more Patients with COVID-19 are at increased risk of thromboembolism. In a recent study of 184 patients with COVID-19, there was a cumulative incidence of venous thromboembolism of 27% and arterial thrombotic events of 3.7%.1 Abnormal coagulation parameters, particularly elevated D-dimer and fibrinogen, have been shown to be associated with poor prognosis in these patients,2 and anticoagulation is associated with decreased mortality in severe COVID-19.3 Antiphospholipid antibodies, mainly lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL), contribute to an acquired prothrombotic state. They are associated with significantly increased risk of arterial, venous, and microvascular thrombosis. The prevalence of LAC or aCL in healthy individuals is 1%-5% with a predominance among females though it may increase in elderly and with chronic disease. Many infections have been shown to be accompanied by an increase in antiphospholipid antibodies, which is often transient, but can persist and trigger thromboembolic events.4 The purpose of this retrospective study at the Shaare Zedek Medical Center (SZMC) in Jerusalem was to determine whether patients with COVID-19 have elevated antiphospholipid antibodies and whether there is a correlation between the level of antiphospholipid antibodies and the severity of the disease. The study was approved by the Ethics Committee of SZMC (approval no. 0139-20-SZMC). Forty-three consecutive patients, 27 male and 16 female, were evaluated for LAC, using the HemosIL dilute Russell viper venom time (dRVVT) screen and HemosIL dRVVT confirm assay and the HemosIL Silica clotting (SCT) screen and HemosIL SCT confirm assay in citrated peripheral blood. The tests were described in ratio and considered positive as follows: dRVVT ratio above 1.22 and SCT ratio above 1.2. Anticardiolipin IGM/IGG and anti-beta-2-glycoprotein IGM/IGG were performed by enzyme-linked immunosorbent assays using ORGENTEC test kits. Incidence of lupus Anticoagulants: 16 of 43 patients (37%) were positive for LAC, 6 of 11 (54%) with mild disease, 2 of 13 (15%) with moderate disease, and 8 of 19 (42%) with severe disease. aCL and anti-β2-glycoprotein I were negative in all patients. All LAC-positive patients were on low molecular weight heparin. Eight patients received prophylactic dose (enoxaparin 40 mg once daily), and eight patients received full anticoagulation (seven patients enoxaparin 1mg/kg twice daily and one patient enoxaparin 1 mg/kg once daily due to renal failure). There was no significant difference in D-dimer, fibrinogen, C-reactive protein, or platelet count between patients positive or negative for LAC (Table 1). Interestingly, in our cohort, LAC was more prevalent in male patients. There is no obvious explanation, though it may be related to male patients being more seriously affected by COVID-19. The occurrence of vascular events was not higher in LACpositive patients although such events were clinically diagnosed in only three patients. This may have been underdiagnosed as patients were not systematically evaluated for thrombotic complications. Microvascular thromboses are difficult to evaluate as they can manifest as organ dysfunction, often impossible to differentiate from other causes without tissue biopsy. An unexpected high incidence of lupus anticoagulant was observed in patients with COVID-19. These results are similar to recently published findings by Bowles et al,5 Harzallah et al6 and de Chambrun et al7 LAC has been reported in 4 out of 21 children suffering from SARS without correlation to thromboembolic events.8 Although intuitively there is a pathophysiologic relationship of APLA with vasculopathy in COVID-19, such an association could not be demonstrated in this cohort of 43 patients, in whom the overall incidence of proven thrombosis was low. Larger studies are needed.

Experimental Hematology, 2021

The Israel Medical Association journal : IMAJ, 2021

With the introduction of tyrosine kinase inhibitors (TKIs) in the management of Philadelphia chro... more With the introduction of tyrosine kinase inhibitors (TKIs) in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the prognosis of patients has improved dramatically. Currently, the standard of care in the frontline setting for fit patients is TKI in combination with chemotherapy. Age-adjusted chemotherapy or corticosteroids alone have been used with TKIs in elderly patients with comorbidities with modest long-term benefit. The primary goal of treatment is the achievement of early deep molecular remission as the achievement of complete molecular remission (CMR) at 3 months has been demonstrated to be predictive of higher long-term survival. The probability of attaining this goal by a more potent TKIs like dasatinib or ponatinib is higher, thus we recommend the use of second- or third-generation TKIs over imatinib. Clinicians should be aware of possible fatal cardiovascular events mainly related to ponatinib. Allogeneic hematopoietic stem cell t...

Background: The COVID‑19 pandemic is an ongoing global pandemic. Jerusalem with its 919,400 inhab... more Background: The COVID‑19 pandemic is an ongoing global pandemic. Jerusalem with its 919,400 inhabitants has a wide variety of populations, of which 62% are Jews (36% ultra-orthodox; 64% non-ultraorthodox) and 38% Arabs which were largely affected by the pandemic. The aim of our study was to understand the different presentations, course and clinical outcomes in these different ethnical and cultural groups in Jerusalem in the COVID-19 pandemic. Methods: We performed a cohort study of all COVID-19 patients admitted between March 9 - July 16, 2020 to the two university medical centers in Jerusalem. Patients were divided according to their religion and ethnicity into 3 main groups: 1) Ultra-Orthodox Jews; 2) other (non-Ultra-Orthodox) Jews and 3) Arabs. Results: Six hundred and two patients comprised the study population. Of them the 361 (60%) were Ultra-Orthodox Jews; 166 (27.5%) non-Ultra-Orthodox Jews and 75 (12.5%) Arabs. The Arab patients were younger than the Ultra-Orthodox Jews a...