Elliott Vichinsky

Publications (81)290.17 Total impact

• Article: The Palatability and Tolerability of Deferasirox Taken With Different Beverages or Foods.

  Stuart L Goldberg, Patricia J Giardina, Deborah Chirnomas, Jason Esposito, Carole Paley, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Deferasirox is a once-daily, oral iron chelator that was developed out of a need for a long-acting, conveniently-administered chelator for patients with transfusional hemosiderosis. The approved mode of administration requires taking deferasirox on an empty stomach with water, apple juice, or orange juice to limit variation in bioavailability. This required administration schedule might not be palatable for patients. Additionally, approximately one-quarter of patients experience mild to moderate gastrointestinal (GI) symptoms, which may pose additional challenges, particularly in the younger and older age ranges. We present a trial to assess the palatability and safety of various administration modes of deferasirox in pediatric and adult patients. PROCEDURES: Participants rated palatability in a 4-week run-in phase, where deferasirox was administered per label. Subsequently, patients rated several administration modes during a 3-month assessment phase. RESULTS: Palatability was more favorable during the assessment phase, with 47% of patient ratings for palatability being favorable while only 38% were favorable during the run-in phase. The most highly rated choice was deferasirox taken with a soft food at breakfast. In addition, there was an indication of improved GI tolerability during the assessment phase (symptoms were reported in 37% of patients during run-in and 32% during the assessment phase; rates of diarrhea decreased significantly). Although trough PK values increased, no major new toxicities were observed. CONCLUSIONS: These data indicate that different administration options may improve palatability and GI tolerability, which could have a positive impact on treatment adherence. (ClinicalTrials.gov number, NCT00845871) Pediatr Blood Cancer 2013;9999:XX-XX. © 2013 Wiley Periodicals, Inc.
  Pediatric Blood & Cancer 04/2013; · 1.89 Impact Factor
• Article: Human T-cell lymphotropic virus type 1 Infection among U.S. Thalassemia Patients.

  William Switzer, Anupama Shankar, Sean Trimble, Alexis A Thompson, Patricia J Giardina, Alan R Cohen, Thomas D Coates, Elliott Vichinsky, Ellis J Neufeld, Jeanne M Boudreaux, Prof Walid Heneine
  [show abstract] [hide abstract]
  ABSTRACT: Thalassemia is an inherited genetic disorder requiring multiple transfusions to treat anemia caused by low hemoglobin levels. Thus, thalassemia patients are at risk for infection with blood-borne pathogens, including human T-cell lymphotropic viruses (HTLV) that are transmitted by transfusion of cellular blood products. Here, we examined the prevalence of HTLV among 234 US thalassemia patients using sera collected in 2008. Sera were tested for antibodies to HTLV-1/2 using EIA and a confirmatory Western blot (WB) that differentiates between HTLV-1 and HTLV-2. Demographic and clinical information were collected at study enrollment, including HIV and HCV status. Three patients (1.3%) were WB-positive; two were HTLV-1 and one could not be serotyped as HTLV-1/2. All three HTLV-positive persons were HIV-1 and one was HCV seropositive. The HTLV seroprevalence was higher than that of HIV-1 (0.85%) and lower than HCV (18.8%) in this population. All three patients (ages 26-46 years) were diagnosed with beta-thalassemia shortly after birth and have since been receiving multiple transfusions annually. Two of the HTLV-positive patients confirmed receiving transfusions before HTLV blood screening was implemented in 1988. We identified a substantial HTLV-1 seroprevalence in US thalassemia patients that is much greater than that seen in blood donors. Our findings highlight the importance of HTLV testing of patients with thalassemia and other diseases requiring multiple transfusions, especially in recipients of unscreened transfusions. In addition, appropriate counseling and follow-up of HTLV-infected patients is warranted.
  AIDS research and human retroviruses 02/2013; · 2.18 Impact Factor
• Article: Treatment of Classic Pantothenate Kinase-Associated Neurodegeneration with Deferiprone and Intrathecal Baclofen.

  Napala R Pratini, Nancy Sweeters, Elliott Vichinsky, Jacob A Neufeld
  [show abstract] [hide abstract]
  ABSTRACT: Neurodegeneration with brain iron accumulation (NBIA) describes a heterogeneous family of diseases characterized by high brain iron, particularly in the basal ganglia. The most common manifestation of childhood NBIA is classic pantothenate kinase-associated neurodegeneration (PKAN), a severe, progressive type of autosomal recessive neuroaxonal dystrophy characterized by early onset of symptoms (as opposed to atypical PKAN, with an average age of onset of 14 yrs). There is currently no established therapy for the disease. Intrathecal baclofen has been reported to improve ease of care and dystonia in patients with PKAN. Deferiprone, an iron chelator, has been shown to be safe and tolerable in patients with PKAN as well as effective in reducing brain iron accumulation, as measured by magnetic resonance imaging. This case report highlights the potency of combining intrathecal baclofen and oral deferiprone in a patient with classic PKAN. Although treatment with deferiprone alone was not attempted, this combination therapy seems to be more efficacious than treatment with only intrathecal baclofen.
  American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 01/2013; · 1.56 Impact Factor
• Article: Pain in thalassaemia: the effects of age on pain frequency and severity.

  Dru Haines, Marie Martin, Susan Carson, Olivia Oliveros, Sage Green, Thomas Coates, Jennifer Eile, Leann Schilling, Bogan Dinu, Tito Mendoza, Eric Gerstenberger, Felicia Trachtenberg, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Pain is not a symptom generally associated with thalassaemia. However, providers have noted increasing patient reports of pain, creating an impetus for this prospective, observational assessment of pain in thalassaemia patients. The primary study goals were to assess pain prevalence, severity, location, and potential risk factors. This was a multicentre, prospective study of thalassaemia patients receiving care at 12 Thalassaemia Clinical Research Network sites. Pain was assessed using the Brief Pain Inventory. Two hundred and fifty-two thalassaemia patients ranging in age from 12 to 71 years (mean 28·8) were enrolled. Sixty-four per cent reported experiencing pain during the last 4 weeks, 22% of whom reported pain on a daily basis. Ordinal regression analysis of pain ratings demonstrated significant (P < 0·001) correlation of increased age with increased pain, irrespective of diagnosis, transfusion status, gender, bone density, chelator type or iron overload. Eighty-one per cent reported having pain for 1 year or longer and 31% reported pain for five or more years. Pain is a major cause of morbidity and an unrecognized problem for patients with thalassaemia. Age is the strongest predictor of frequency and severity. Little else is known about the aetiology and predictors of this pain syndrome.
  British Journal of Haematology 12/2012; · 4.94 Impact Factor
• Article: Increased leucocyte apoptosis in transfused β-thalassaemia patients.

  Patrick B Walter, John Porter, Patricia Evans, Janet L Kwiatkowski, Ellis J Neufeld, Thomas Coates, Patricia J Giardina, Robert W Grady, Elliott Vichinsky, Nancy Olivieri, Felicia Trachtenberg, Daniele Alberti, Ellen Fung, Bruce Ames, Annie Higa, Paul Harmatz
  [show abstract] [hide abstract]
  ABSTRACT: This exploratory study assessed apoptosis in peripheral blood leucocytes (PBL) from β-thalassaemia patients receiving chronic transfusions and chelation therapy (deferasirox or deferoxamine) at baseline, 1, 6, and 12 months. At baseline, thalassaemic PBLs presented 50% greater levels of Bax (BAX), 75% higher caspase-3/7, 48% higher caspase-8 and 88% higher caspase-9 activities and 428% more nucleosomal DNA fragmentation than control subjects. Only neutrophils correlated significantly with apoptotic markers. Previously, we showed that over the treatment year, hepatic iron declined; we now show that the ratio of Bax/Bcl-2 (BCL2), (-27·3%/year), and caspase-9 activity (-13·3%/year) declined in both treatment groups, suggesting that chelation decreases body iron and indicators of PBL apoptosis.
  British Journal of Haematology 12/2012; · 4.94 Impact Factor
• Article: Combined chelation therapy with deferasirox and deferoxamine in thalassemia.

  Ashutosh Lal, John Porter, Nancy Sweeters, Vivian Ng, Patricia Evans, Lynne Neumayr, Gregory Kurio, Paul Harmatz, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30mg/kg daily) and deferoxamine (DFO, 35-50mg/kg on 3-7days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12months of therapy, median liver iron concentration decreased by 31% from 17.4mg/g (range 3.9-38.2mg/g) to 12.0mg/g (range 0.96-26.7mg/g, p<0.001). Median ferritin decreased by 24% from 2465ng/mL (range 1110-10,700ng/mL) to 1875ng/mL (range 421-5800ng/mL, p=0.002). All 6 subjects with elevated myocardial iron showed improvement in MRI T2* (p=0.031). The mean±S.E. plasma non-transferrin-bound iron (NTBI) declined from 3.10±0.25μM to 2.15±0.29μM (p=0.028). The administration of DFX during infusion of DFO further lowered NTBI (-0.28±0.08μM, p=0.004) and labile plasma iron (LPI, -0.03±0.01μM, p=0.006). The simultaneous administration of DFO and DFX rapidly reduced systemic and myocardial iron, and provided an excellent control of the toxic labile plasma iron species without an increase in toxicity. This trial was registered at www.clinicaltrials.gov as NCT00901199.
  Blood Cells Molecules and Diseases 11/2012; · 2.35 Impact Factor
• Article: Lower alloimmunization rates in pediatric sickle cell patients on chronic erythrocytapheresis compared to chronic simple transfusions.

  Shannon Kelly Wahl, Alicia Garcia, Ward Hagar, Ginny Gildengorin, Keith Quirolo, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Erythrocytapheresis (ECP), automated red blood cell exchange, is increasingly being used for chronic transfusion therapy in sickle cell disease (SCD) as it is an isovolumetric transfusion, is more effective in lowering hemoglobin (Hb)S, and can limit iron overload. Because ECP requires increased blood exposure compared to simple transfusions there is concern for increased transfusion complications, including alloimmunization. We compared alloimmunization rates between patients receiving simple or exchange chronic transfusions. STUDY DESIGN AND METHODS: Data were retrospectively collected for 45 SCD patients (n = 23 simple, n = 22 ECP) on a chronic transfusion program as of December 2010 to determine the rate of antibody formation (antibodies formed per 100 units transfused). RESULTS: The 45 patients received 10,949 units and formed six new alloantibodies during the study period (1994-2010); therefore, the overall alloimmunization rate was 0.055 alloantibodies per 100 U. There were three antibodies formed in three patients on ECP, one allo (anti-rh(i) ) and two autoantibodies. There were six antibodies in four patients on a simple transfusion program, five allo (anti-Le(a) , M, D, C, and Kp(a) ) and one autoantibody. The ECP group received significantly more blood (338.5 units/patient vs. 152.2 units/patient, p = 0.001). The rate of antibody formation (auto plus allo) was 0.040 antibodies per 100 U in the ECP group and 0.171 antibodies per 100 U in the simple transfusion group (p = 0.04). The alloantibodies formed per 100 units was 0.013 in the ECP group and 0.143 in the simple transfusion group (p = 0.03). CONCLUSION: Chronic ECP should be considered in patients requiring optimal management of HbS levels and iron burden. Concerns about increased alloimmunization with ECP may be unjustified.
  Transfusion 04/2012; · 3.22 Impact Factor
• Source

  Available from: Stephen Embury

  Article: A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease.

  Abdullah Kutlar, Kenneth I Ataga, Lillian McMahon, Joanna Howard, Frederic Galacteros, Ward Hagar, Elliott Vichinsky, Anthony T W Cheung, Neil Matsui, Stephen H Embury
  [show abstract] [hide abstract]
  ABSTRACT: Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease (SCD) [1,2]. Most notably, occlusion of flow in the microvasculature causes the acute pain crises [3] that are the commonest cause for patients with SCD to seek medical attention [4] and major determinants of their quality of life [5]. Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD. A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD. An in vitro study showed that Pentosan Polysulfate Sodium (PPS) had greater P-selectin blocking activity than heparin. A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD. A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD. These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD. They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD.
  American Journal of Hematology 02/2012; 87(5):536-9. · 4.67 Impact Factor
• Article: The mediating effects of family functioning on psychosocial outcomes in healthy siblings of children with sickle cell disease

  Jeffrey I. Gold PhD, Marsha Treadwell PhD, Lina Weissman PhD, Elliott Vichinsky MD, Jeffrey I. Gold, Marsha Treadwell, Lina Weissman, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Background Children with siblings coping with chronic illness experience stresses and disruptions in daily life as families work together to care for the affected child. Research suggests that children and adolescents with sickle cell disease (SCD) may be at risk for adjustment problems, impaired psychosocial functioning, and reduced quality of life. These potential stressors affect the child with SCD as well as their caregivers and other family members. This study examined the role of family functioning on the psychosocial functioning of healthy siblings of children with SCD.ProcedureParticipants were 65 healthy African–American siblings of children with SCD with a mean age of 11.19 years (range: 7–16) and their primary caregiver. Caregivers completed questionnaires assessing family functioning and child adjustment including demographic surveys, the Family Relations Scale (FRS), and the Child Behavior Checklist (CBCL).ResultsIncreased number of emergency room visits (β = −0.28, P < 0.05) predicted poor psychosocial adjustment in siblings. Family functioning mediated this effect (β = 0.27; P < 0.05). High levels of family expressiveness (total score, r = −0.34; P < 0.01), support (total score, r = −0.54; P = 0.001), and low levels of family conflict (total score, r = 0.41; P < 0.001) were associated with improved adjustment among healthy siblings of children with SCD.Conclusions Awareness of the possible negative psychosocial outcomes of living with a sister or a brother with SCD is important for clinicians. In particular, interventions that focus on family expressiveness, support, and conflict are indicated for this population. Pediatr Blood Cancer 2011; 57: 1055–1061. © 2011 Wiley-Liss, Inc.
  Pediatric Blood & Cancer 11/2011; 57(6):1055 - 1061. · 1.89 Impact Factor
• Article: Hb E/beta-thalassaemia: a common & clinically diverse disorder.

  Nancy F Olivieri, Zahra Pakbaz, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is the genotype responsible for approximately one-half of all severe beta-thalassaemia worldwide. The disorder is characterized by marked clinical variability, ranging from a mild and asymptomatic anaemia to a life-threatening disorder requiring transfusions from infancy. The phenotypic variability of Hb E/β-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive recommendations for the optimal management of patients. Genetic factors influencing the severity of this disorder include the type of beta-thalassaemia mutation, the co-inheritance of alpha-thalassaemia, and polymorphisms associated with increased production of foetal haemoglobin. Other factors, including a variable increase in serum erythropoietin in response to anaemia, previous or ongoing infection with malaria, previous splenectomy and other environmental influences, may be involved. The remarkable variation, and the instability, of the clinical phenotype of Hb E beta-thalassaemia suggests that careful tailoring of treatment is required for each patient, and that therapeutic approaches should be re-assessed over-time.
  The Indian journal of medical research 10/2011; 134:522-31. · 1.84 Impact Factor
• Article: A pilot study of the short-term use of simvastatin in sickle cell disease: effects on markers of vascular dysfunction.

  Carolyn Hoppe, Frans Kuypers, Sandra Larkin, Ward Hagar, Elliott Vichinsky, Lori Styles
  [show abstract] [hide abstract]
  ABSTRACT: Sickle cell disease (SCD) is characterized by progressive vascular injury and its pathophysiology is strikingly similar to that of atherosclerosis. Statins decrease inflammation and improve endothelial function in cardiovascular disease, but their effect in SCD is not known. In this pilot study, we examined the safety and effect of short-term simvastatin on biomarkers of vascular dysfunction in SCD. We treated 26 SCD patients with simvastatin, 20 or 40 mg/d, for 21 d. Plasma nitric oxide metabolites (NOx), C-reactive protein (CRP), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), tissue factor (TF) and vascular endothelial growth factor (VEGF) were analyzed and responses to simvastatin were compared between the two treatment groups. Simvastatin increased NOx levels by 23% in the low-dose (P =0·01) and 106% in the moderate-dose (P =0·01) groups, and by 52% overall (P=0·0008). CRP decreased similarly in both dose groups and by 68% overall (P =0·02). Levels of IL-6 decreased by 50% (P=0·04) and 71% (P<0·05) in the low- and moderate-dose groups, respectively. Simvastatin had no effect on VEGF, VCAM1 or TF. Simvastatin was well-tolerated and safe. Our preliminary findings showing a dose-related effect of simvastatin on levels of NOx, CRP and IL-6 suggest a potential therapeutic role for simvastatin in SCD.
  British Journal of Haematology 06/2011; 153(5):655-63. · 4.94 Impact Factor
• Source

  Available from: Gian Luca Forni

  Article: Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

  Elliott Vichinsky, Françoise Bernaudin, Gian Luca Forni, Renee Gardner, Kathryn Hassell, Matthew M Heeney, Baba Inusa, Abdullah Kutlar, Peter Lane, Liesl Mathias, John Porter, Cameron Tebbi, Felicia Wilson, Louis Griffel, Wei Deng, Vanessa Giannone, Thomas Coates
  [show abstract] [hide abstract]
  ABSTRACT: To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years.
  British Journal of Haematology 05/2011; 154(3):387-97. · 4.94 Impact Factor
• Source

  Available from: Robert C. Yamashita

  Article: Iron chelation adherence to deferoxamine and deferasirox in thalassemia.

  Felicia Trachtenberg, Elliott Vichinsky, Dru Haines, Zahra Pakbaz, Lauren Mednick, Amy Sobota, Janet Kwiatkowski, Alexis A Thompson, John Porter, Thomas Coates, Patricia J Giardina, Nancy Olivieri, Robert Yamashita, Ellis J Neufeld
  [show abstract] [hide abstract]
  ABSTRACT: The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators.
  American Journal of Hematology 05/2011; 86(5):433-6. · 4.67 Impact Factor
• Article: The mediating effects of family functioning on psychosocial outcomes in healthy siblings of children with sickle cell disease.

  Jeffrey I Gold, Marsha Treadwell, Lina Weissman, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Children with siblings coping with chronic illness experience stresses and disruptions in daily life as families work together to care for the affected child. Research suggests that children and adolescents with sickle cell disease (SCD) may be at risk for adjustment problems, impaired psychosocial functioning, and reduced quality of life. These potential stressors affect the child with SCD as well as their caregivers and other family members. This study examined the role of family functioning on the psychosocial functioning of healthy siblings of children with SCD. Participants were 65 healthy African-American siblings of children with SCD with a mean age of 11.19 years (range: 7-16) and their primary caregiver. Caregivers completed questionnaires assessing family functioning and child adjustment including demographic surveys, the Family Relations Scale (FRS), and the Child Behavior Checklist (CBCL). Increased number of emergency room visits (β = -0.28, P < 0.05) predicted poor psychosocial adjustment in siblings. Family functioning mediated this effect (β = 0.27; P < 0.05). High levels of family expressiveness (total score, r = -0.34; P < 0.01), support (total score, r = -0.54; P = 0.001), and low levels of family conflict (total score, r = 0.41; P < 0.001) were associated with improved adjustment among healthy siblings of children with SCD. Awareness of the possible negative psychosocial outcomes of living with a sister or a brother with SCD is important for clinicians. In particular, interventions that focus on family expressiveness, support, and conflict are indicated for this population.
  Pediatric Blood & Cancer 02/2011; 57(6):1055-61. · 1.89 Impact Factor
• Article: Red cell alloimmunization in a diverse population of transfused patients with thalassaemia.

  Alexis A Thompson, Melody J Cunningham, Sylvia T Singer, Ellis J Neufeld, Elliott Vichinsky, Robert Yamashita, Patricia Giardina, Hae-Young Kim, Felicia Trachtenberg, Janet L Kwiatkowski
  [show abstract] [hide abstract]
  ABSTRACT: Red blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre-storage screening has resulted in decreased transfusion-transmitted infections, but anti-RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions. Allo- and autoantibody rates were compared with respect to splenectomy status, ethnicity, diagnosis, duration of transfusions, treatment centre, and age at transfusion initiation, together with rates before and after 1990, when leucoreduction methods were routine at thalassaemia treatment centres. Allo- and autoantibodies were reported in 115 (16·5%) and 34 (4·9%) subjects, respectively. Splenectomized patients were more likely to have alloantibodies [odds ratio (OR) = 2·528, P ≤ 0·0001], or autoantibodies (OR = 2·590, P = 0·0133). Alloantibodies occurred in 19 of 91 (21%) splenectomized subjects who started transfusion after 1990, and only 18 of 233 (7·7%) nonsplenectomized subjects (P < 0·001). Data from this study demonstrate that RBC antibodies continue to develop in chronically transfused thalassaemia patients at a high rate. Splenectomy preceded the development of antibodies in most cases. Increased rates of RBC sensitization among splenectomized patients is concerning and deserves further study.
  British Journal of Haematology 02/2011; 153(1):121-8. · 4.94 Impact Factor
• Article: HbE/β-thalassemia: basis of marked clinical diversity.

  Nancy F Olivieri, Zahra Pakbaz, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Hemoglobin E thalassemia accounts for about one-half of all cases of severe beta thalassemia. There is marked variability in its clinical severity ranging from an asymptomatic to a transfusion-dependent phenotype. The phenotypic variability and inadequate longitudinal data present challenges in determining the optimal management of patients. This article summarizes findings on the natural history of Hemoglobin E thalassemia and some factors responsible for its clinical heterogeneity. Major genetic factors include the type of beta thalassemia mutation, the co-inheritance of alpha thalassemia, and polymorphisms associated with increased synthesis of fetal hemoglobin. Other factors, including response to anemia, and the influence of infection with malaria and other environmental influences, may be important. The remarkable variation and instability of clinical phenotypes in Hemoglobin E thalassemia require individual management plans for each patient, which should be reassessed over time.
  Hematology/oncology clinics of North America 12/2010; 24(6):1055-70. · 2.05 Impact Factor
• Source

  Available from: Ellis J Neufeld

  Article: A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload.

  Hugh Young Rienhoff, Vip Viprakasit, Lay Tay, Paul Harmatz, Elliott Vichinsky, Deborah Chirnomas, Janet L Kwiatkowski, Amy Tapper, William Kramer, John B Porter, Ellis J Neufeld
  [show abstract] [hide abstract]
  ABSTRACT: There is still a clinical need for a well-tolerated and safe iron chelator for the treatment of transfusional iron overload. We describe the pharmacokinetic properties and safety data after 7 days of dosing of FBS0701, a novel oral, once-daily iron chelator. This phase 1b dose-escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload, was conducted in 16 adult patients with iron overloaded consequent to transfusions. FBS0701 was given daily for 7 days at doses up to 32 mg/kg and was well tolerated at all dose levels. Pharmacokinetics showed dose-proportionality. The maxium plasma concentration (C(max)) was reached within 60-90 minutes of dosing and the drug was rapidly distributed at the predicted therapeutic doses. The plasma elimination half-life (t(1/2)) was approximately 19 hours. There were no serious adverse events associated with the drug. Conclusions On the basis of these safety and pharmacokinetic data, FBS0701 warrants further clinical evaluation in patients with transfusional iron overload. (Clinicaltrials.gov identifier: NCT01186419).
  Haematologica 12/2010; 96(4):521-5. · 6.42 Impact Factor
• Article: Novel influenza A (H1N1) viral infection in pediatric patients with sickle-cell disease.

  James E Jacobs, Keith Quirolo, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: The 2009 novel influenza A (H1N1) pandemic has had profound public health implications all over the world. The majority of patients infected with the novel strain have recovered uneventfully. However, certain populations have been defined who appear to be at increased risk of complications due to H1N1 infections. This review summarizes the clinical course of five patients with sickle cell, four of whom had confirmed H1N1 infection, and one whom had a presumed H1N1 infection. The clinical presentation, hospital course, and treatment of five pediatric patients with sickle-cell disease and H1N1 infection were reviewed retrospectively. In this case series, our patients experienced complications such as the acute chest syndrome, acute marrow suppression of red cell production, pain crisis, and hematuria. In this population, who are at increased risk for bacterial superinfection as well as complications from the influenza virus itself, vigilance toward diagnosis and aggressive treatment will continue to be important as long as the novel virus is in circulation.
  Pediatric Blood & Cancer 10/2010; 56(1):95-8. · 1.89 Impact Factor
• Source

  Available from: Robert C. Yamashita

  Article: Education and employment status of children and adults with thalassemia in North America.

  Zahra Pakbaz, Marsha Treadwell, Hae-Young Kim, Felicia Trachtenberg, Nagina Parmar, Janet L Kwiatkowski, Melody J Cunningham, Marie Martin, Nancy Sweeters, Ellis J Neufeld, Patricia J Giardina, Nancy Olivieri, Robert C Yamashita, Elliott Vichinsky
  [show abstract] [hide abstract]
  ABSTRACT: Advances in the management of thalassemia have resulted in increased life expectancy and new challenges. We conducted the first survey of education and employment status of people with thalassemia in North America. A total of 633 patients (349 adults and 284 school age children) enrolled in the Thalassemia Clinical Research Network (TCRN) registry in Canada and the U.S. were included in the data analysis. Predictors considered for analysis were age, gender, race/ethnicity, site of treatment (Canada vs. United States), transfusion and chelation status, serum ferritin, and clinical complications. Seventy percent of adults were employed of which 67% reported working full-time. Sixty percent had a college degree and 14% had achieved some post-college education. Eighty-two percent of school age children were at expected grade level. In a multivariate analysis for adults, Whites (OR = 2.76, 95% CI: 1.50-5.06) were more likely to be employed compared to Asians. Higher education in adults was associated with older age (OR = 1.67, 95% CI: 1.29-2.15), female gender (OR = 2.08, 95% CI: 1.32-3.23) and absence of lung disease (OR = 14.3, 95% CI: 2.04-100). Younger children (OR = 5.7 for 10-year increments, 95% CI: 2.0-16.7) and Canadian patients (OR = 5.6, 95% CI: 1.5-20) were more likely to be at the expected education level. Neither transfusion nor chelation was associated with lower employment or educational achievement. Individuals with thalassemia in North America can achieve higher education; however, full-time employment remains a problem. Transfusion and chelation do not affect employment or education status of this patient population.
  Pediatric Blood & Cancer 10/2010; 55(4):678-83. · 1.89 Impact Factor
• Article: Fertility potential in thalassemia major women: current findings and future diagnostic tools.

  Sylvia T Singer, Nancy Sweeters, Olivia Vega, Annie Higa, Elliott Vichinsky, Marcelle Cedars
  [show abstract] [hide abstract]
  ABSTRACT: Preserving fertility, preventing early menopause, and predicting reproductive ability have become crucial for many adult thalassemia major females. Luteinizing hormone/follicle-stimulating hormone (LH/FSH) and estradiol, commonly used for assessment of fertility potential in thalassemia, have a poor predictive value. Current reproductive practice uses markers of ovarian reserve testing, which were not yet studied in thalassemia women. We explored the relationship between liver iron concentration (LIC) and fertility status in 26 females (mean 30 years old). Seventeen (65%) of them experienced primary or secondary amenorrhea. Levels of LH/FSH and estradiol were low or undetectable in 48% and 35% of patients, respectively and did not correlate with age, presence of amenorrhea, and LIC. This further addresses the need for utilization of current available methods for assessment of fertility capacity in thalassemia, which will also allow future correlation with pituitary iron measures by MRI as well as early intervention for fertility preservation.
  Annals of the New York Academy of Sciences 08/2010; 1202:226-30. · 3.15 Impact Factor