scholarly journals CURING HEMOGLOBINOPATHIES: CHALLENGES AND ADVANCES OF CONVENTIONAL AND NEW GENE THERAPY APPROACHES.

2019 ◽  
Vol 11 (1) ◽  
pp. e2019067 ◽  
Author(s):  
Irene Motta ◽  
Valentina Ghiaccio ◽  
Andrea Cosentino ◽  
Laura Breda
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Gene Therapy ◽  
Bone Marrow ◽  
Iron Chelation ◽  
Beta Thalassemia ◽  
Allogenic Bone ◽  
Number Of Patients ◽  
Monogenic Diseases

Inherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD) are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%. With migration they are becoming more common worldwide, making their management and care an increasing concern for health care systems. BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory haemopoietic expansion. Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The current available treatment for TDT is lifelong transfusions and iron chelation therapy or allogenic bone marrow as curative option. SCD affects 300 million people worldwide  and severely impacts the quality of life of patients, who experience unpredictable, recurrent acute and chronic severe pain, stroke, infections, pulmonary disease, kidney disease, retinopathy, and other complications. While survival has been dramatically extended, quality of life is markedly reduced by disease- and treatment-associated morbidity. The development of safe, tissue specific and efficient vectors, and efficient gene editing technologies have led to the development of several gene therapy trials for BT and SCD. Yet, the complexity of the approach presents its hurdles. Fundamental factors at play include the requirement for myeloablation on a patient with a benign disease, the age of the patient and consequent bone marrow microenvironment. A successful path from proof-of-concept studies to commercialization must render gene therapy a sustainable and accessible approach for a large number of patients. Furthermore, the cost of these therapies is a considerable challenge for the health care system. While new promising therapeutic options are emerging and many others are on the pipeline5, gene therapy can potentially cure patients. We herein provide an overview of the most recent potentially curative therapies for hemoglobinopathies and a summary of the challenges that these approaches entail.

Factors Impacting Quality of Life in Thalassemia Patients; Results from the Intercontinenthal Collaborative Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3633-3633 ◽  
Author(s):  
Ali Amid ◽  
Rebecca Leroux ◽  
Manuela Merelles-Pulcini ◽  
Saeed Yassobi ◽  
Antoine N Saliba ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Social Support ◽  
Health Care ◽  
Research Funding ◽  
Beta Thalassemia ◽  
Transfusion Therapy ◽  
The Past ◽  
Clinical Complications ◽  
Number Of Patients

Abstract Thalassemia is one of the most common causes of inherited anemia worldwide. While significant advances has been made in clinical management of thalassemia patients over the past few decades, our knowledge on the factors affecting the quality of life of thalassemia patients is limited. The "IntercontinThal Study" is a collaborative effort to study the quality of life (QoL) and quality of care of thalassemia patients in populations across diverse social and health care systems. Data presented here are from the three participating centers in Canada, Lebanon and Iran. We have gathered study data through: a) QoL questionnaire SF-36 completed by patients, b) a specifically designed and validated questionnaire completed by patients which addressed patient's social status (marriage/relationship status, education, employment status, and access to social support and health care), and c) review of the patients' charts using a data collection form. This form included: patients' demographics, specifics of transfusion therapy and iron chelation, thalassemia-related and other clinical complications (endocrinopathies, bone disease, cardiac disease, hemolysis-related complications, etc.), tissue iron content (liver and cardiac) and/or serum ferritin within the past three years, and splenectomy status. All study questionnaires were translated into Persian (for Iranian patients) and Arabic (for Lebanese patients). Due to the variety of the clinical complications, all clinical complications were aggregated together for statistical analysis. We used univariate and multivariate regression analysis to study the association of predictors and patients' QoL Mental Component Summary (MCS) Score. Ninety seven patients [46 female, 59 transfusion-dependent beta-thalassemia (TDT) and 38 non-transfusion-dependent beta-thalassemia (NTDT)] were included in the analysis. All patients were older than 18 years of age (Mean 32 years, SD: 7 years). In univariate analysis age, access to social support and health care, marriage status, liver iron concentration and ferritin (strongly correlated with each other), and disease-related complications were found to be predictor of QoL MCS scores. In NTDT patients, splenectomy and lower baseline hemoglobin were also significantly associated with reduced QoL. In multivariate analysis, ferritin and age (and clinical complications in TDT patients) were found to independently be associated with reduced QoL. LIC was not found to be an independent factor likely due to the fewer number of patients who had recent LIC assessments. Of interest, patients with NTDT reported better QoL at younger age compared to TDT patients but there was a trend toward worse QoL at older age. Our results provide a better understanding of the factors that affect the QoL of thalassemia patients and highlights the importance of management of body iron in both TDT and specially in NTDT patients. In addition, it confirms the notion that while NTDT patients may not require regular transfusions based on conventional criteria, they may experience significant reduction in QoL especially at older ages. Further efforts to address the health and QoL of NTDT patients are required to improve the outcomes of this often neglected condition. (Funded by a research grant from the Thalassemia Foundation of Canada) Disclosures Taher: Celgene: Research Funding; Novartis: Honoraria, Research Funding.

Quality of Life and Satisfaction with Iron Chelation Therapy in Patients with Beta Thalassemia Major: Results from the ITHACA Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3344-3344 ◽  
Author(s):  
Lorenzo Giovanni Mantovani ◽  
Luciana Scalone ◽  
Simona Ravera ◽  
Diana Rofail ◽  
Maria Domenica Cappellini ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Iron Chelation ◽  
Clinical Effectiveness ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Perceived Effectiveness ◽  
Old Patients ◽  
Sf 36

Abstract Background Patients with beta Thalassemia Major (TM) require life-long blood transfusions, which often cause iron overload that may increase patients’ morbidity and mortality. Iron Chelation Treatment (ICT), aimed to reduce iron overload, is based on 8–12 hour infusions of Deferoxamine (DFO) for 5–7 days/week, and/or Deferiprone (L1) orally administered. Current ICT can be related to low satisfaction, low compliance, and potentially negative consequences on clinical effectiveness, patients’ wellbeing and on healthcare costs. Aims: To investigate the Health-Related Quality-of-Life (HRQoL) of TM patients and their satisfaction with ICT. Methods: The Italian-THAlassemia-Cost-&-Outcomes-Assessment (ITHACA) was a naturalistic multicentre study conducted to evaluate costs, HRQoL, compliance and treatment satisfaction in TM patients undergoing ICT for at least 3 years, enrolled at Italian Thalassemia Care Centers. HRQoL was measured in >14 years old patients with 2 generic instruments: EQ-5D; Short Form-36 (SF-36). To measure satisfaction >12 years old patients received a 28-item instrument consisting of 4 domains: ‘perceived effectiveness’, ‘acceptance’, ‘burden’, and ‘side effects’. Each domain scored from from 1 (very dissatisfied) to 5 (very satisfied). Results Based on 126 patients: median age 29.4 years (12.3–48.5), 49.6% male. At enrolment 48.0% were using DFO, 33.6% L1, 18.4% were treated with DFO+L1. 86.5% of patients had at least one TM-related complication, 13.5% changed treatment regimen at least once in a median of 11.6 months before enrolment. With EQ-5D profile patients reported moderate problems with ‘mobility’ (9.1%), ‘self care’ (0.8%), ‘usual activities’ (23.5%), moderate or severe ‘pain/discomfort’ (60.5%) and ‘anxiety/depression’ (39.5%). Mean EQ-5D-Visual Analogue Scale was 73.0 (30–100). The SF-36 Physical Component Summary mean(SD) score was 47.7(8.4), while the mean score estimated in the Italian general population comparable for age and sex is 53.3; the Mental Component Summary mean(SD) score in TM patients was 45.1(8.8), while the Italian general population mean score was 47.7. Mean satisfaction scores were 4.29 (perceived effectiveness), 3.37 (acceptance), 3.87 (burden), and 3.57 (side effects). Simple linear regression analysis showed that satisfaction with burden (r2=12.6%, p<0.0001), side effects (r2=12.3%, p<0.0001) and acceptance(r2=11.3%, p=0.0001), are positively associated with the adherence item ‘never thinking about stopping medication’ (p<0.0001 in both cases). Conclusions: TM patients on ICT have impaired levels of physical and mental HRQoL. Therapies improving patients’ satisfaction and compliance to ICT may have positive consequences not only on clinical effectiveness but also on overall patients’ well-being.

Quality of Life in Adult Recipients of Bone Marrow Transplantation

1994 ◽  
Vol 75 (1) ◽  
pp. 323-328 ◽  
Author(s):  
Nola M. Litwins ◽  
James R. Rodrigue ◽  
Roy S. Weiner
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Coping Styles ◽  
Marrow Transplant ◽  
Transplant Recipients ◽  
Conventional Chemotherapy ◽  
Passive Coping

Quality of life, coping styles, and satisfaction with health care were assessed in 32 bone marrow transplant recipients and 22 conventional chemotherapy recipients. Subjects reported having generally good quality of life with no significant differences in quality of life or coping styles between the two groups. Quality of life was not significantly associated with age, socioeconomic status, time since diagnosis, or time since last treatment, although lower scores were associated with a passive coping style. Interestingly, bone marrow transplant recipients reported greater over-all satisfaction with health care and more contentment with the cost and convenience of health-care delivery than did conventional chemotherapy recipients.

scholarly journals Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 361-370 ◽  
Author(s):  
John Porter
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
Gene Therapy ◽  
Clinical Trials ◽  
Transforming Growth Factor ◽  
Transfusion Therapy ◽  
Hematopoietic Stem ◽  
Transfusion Requirements ◽  
Long Term Treatment

Abstract Transfusion combined with chelation therapy for severe β thalassemia syndromes (transfusion-dependent thalassemia [TDT]) has been successful in extending life expectancy, decreasing comorbidities and improving quality of life. However, this puts lifelong demands not only on the patients but also on the health care systems that are tasked with delivering long-term treatment and comprehensive support. Prevention programs and curative approaches are therefore an important part of overall strategy. Curative treatments alter the dynamic of a patient's health care costs, from financial commitment over 50 years, into a potential “one-off” investment. Since the 1980s, this has usually been available only to the 30% or so of young children with matched sibling donors. By improving the safety of matched related donors and haploidentical hematopoietic stem cell transplants, the potential size of the donor pool for curative therapies may be increased. Recent advances in gene therapy demonstrate that even patients lacking a matched donor can be rendered transfusion independent with an autograft of genetically modified autologous stem cells, with a low short-term risk. Noncurative treatments are also of potential value by decreasing use of blood and chelators and decreasing hospital visits. An example is luspatercept, an activin-receptor trap that modifies transforming growth factor-β signaling, thereby increasing the efficiency of erythropoiesis. This has entered phase 3 clinical trials for TDT and non-TDT and, usefully increases in both Hb and quality of life in non-TDT as well as decreasing transfusion requirements in TDT. Other novel noncurative treatments are entering clinical trials such improvement of erythropoiesis through pharmacological manipulation of hepcidin and iron metabolism.

scholarly journals Comparative Effects of Three Iron Chelation Therapies on the Quality of Life of Greek Patients with Homozygous Transfusion-Dependent Beta-Thalassemia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Vasilis Goulas ◽  
Alexandra Kourakli-Symeonidis ◽  
Charalambos Camoutsis
Keyword(s):  
Quality Of Life ◽  
Iron Chelation ◽  
Self Esteem ◽  
Physical Component Summary Score ◽  
Summary Score ◽  
Beta Thalassemia ◽  
Adherence To Treatment ◽  
Treatment Rate ◽  
Treatment Benefits

This prospective study assessed the quality of life of patients with homozygous transfusion-dependent beta-thalassemia in Greece receiving three different iron chelation treatments. Patients enrolled were receiving one of the following chelation therapies: deferoxamine (n=21), deferasirox (n=75), or deferoxamine in combination with deferiprone (n=39). The three groups were compared in terms of their quality of life, satisfaction and adherence to treatment, control of their health, and self-esteem through the completion of five questionnaires. A higher percentage of patients receiving deferoxamine felt that their treatment negatively influenced their body and skin appearance and limited their ability to work, attend school, and perform daily tasks (P=0.0066). The adherence to treatment rate and self-esteem were the lowest in the deferoxamine group (P<0.05). The deferoxamine group also had the lowest physical component summary score in the SF-36 questionnaire (P=0.014). This study suggests that the quality of life of beta-thalassemia patients receiving chelation therapy is dependent on the type of iron chelation treatment they receive. The study provides insight into important factors associated with the quality of life of these patients, which are essential for developing a more suitable clinical support team and counseling in order to maximize the treatment benefits for these patients in daily clinical practice.

scholarly journals Low Impact of Genetic Modifiers on the Phenotype of Homozygous Beta Thalassemia in the Last Decennial Cohort of Thalassemia Newborns in Sardinia

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 951-951
Author(s):  
Paolo Moi ◽  
Matteo Marcello ◽  
Stefania Satta ◽  
Laura Manunza ◽  
Franca Rosa De Martis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Conflicts Of Interest ◽  
Time Lag ◽  
Clinical Decision ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Genetic Modifiers ◽  
Thalassemia Intermedia ◽  
Number Of Patients

Abstract Historically 15-20% of homozygous ß-thalassemia in Sardinia developed the phenotype of thalassemia intermedia not requiring transfusion for survival. However, this category of patients has broad and heterogeneous spectrum severity, embracing truly mild thalassemia patients and patients with severity similar to thalassemia major. Known genetic modifiers that ameliorate the severity of b-thalassemia are the mild genotypes of ß+-thalassemia, the coinheritance of α-thalassemia, of hereditary persistence of fetal hemoglobin (HPFH) and of polymorphic variants in the BCL11a, MYB and HBG1 genes. All together this modifiers allow the calculation of a genetic score of severity that predicts the possibility of remaining transfusion free at a given age, likely aiding in the clinical decision to start or delay the initiation of a stable transfusion program. In this study we planned to evaluate the ameliorating effects of these genetic modifiers on the thalassemia phenotype by prospectively evaluating 51 homozygous ß-thalassemia newborns followed at our Institution in the last ten years. All newborns were genotyped soon after birth for all known genetic modifiers and monitored clinically for the appearance of anemia or other complications with monthly check-ups from birth until they required transfusions, according to the TIF guidelines. In this decennial cohort, all but 2 patients younger than 20 months started a regular transfusion program before 36 months of age. Hence, the percentage of thalassemia intermedia in Sardinia has dropped in the last decade from 18 to 4% and might even reach 0% if the 2 patients non yet transfused will transfuse within the next year. This shift from thalassemia intermedia to major is mainly accounted for by the great improvement in mortality, morbility and quality of life for thalassemia major compared to thalassemia intermedia patients who frequently develop difficult to manage complications with advancing age. In the cohort, the reason for start of blood transfusions was anemia lower than 7gr/dl in 14 % of cases and the appearance of skeletal modifications or growth failure in the remaining 84% of patients. Thus, differently from the past, most patients were transfused despite an acceptable grade of anemia. As expected, the presence of a greater number of genetic modifiers significantly correlated with a delay in the time lag to the first transfusion. Even better positive correlation (p&lt;0.0009) was found between the number of genetic modifiers and the levels of hemoglobin before beginning transfusion, confirming the positive influence of genetic modifiers on hemoglobin production. Since the start of transfusions, blood consumption did not positively correlated with the number of favorable genetic hits, but showed a trend toward significance, likely to achieve significance with increasing number of patients. Since the clinical decision to transfuse was taken mainly on the highly subjective parameter of appearance of skeletal modifications, it is possible that were transfused even the patients likely to have mild thalassemia intermedia and a good quality of life for most of their lifespan. We propose that at least the thalassemia patients with the best hemoglobin values (higher than 9 gr/dl) and a favorable background with at least 2 genetic modifiers (12% of our ߰-thalassemia newborns) should be more carefully evaluated for the possibility to evolve into a mild thalassemia intermedia phenotype with good quality of life for most of their lifespan. Disclosures No relevant conflicts of interest to declare.

Palliative radiotherapy referrals in the last days of cancer patients' life: Could we do better?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24008-e24008
Author(s):  
Leora Brazg Ferro ◽  
Eliya Shachar ◽  
Orit Gutfeld ◽  
Ido Wolf ◽  
Yasmin Natan Oz
Keyword(s):  
Quality Of Life ◽  
Health Care ◽  
End Of Life ◽  
Health Care System ◽  
Treatment Plan ◽  
Palliative Radiotherapy ◽  
Palliative Radiation ◽  
Number Of Patients ◽  
Care System

e24008 Background: The role of active cancer therapy towards the end of life (EOL) is debatable and may even be considered harmful. While palliative radiotherapy may be highly effective in reducing cancer-related symptoms of advanced disease, the beneficial effects are usually at least 2-4 weeks from completion of treatment. Thus, radiotherapy administered at the end of life is often ineffective, and may actually impair quality of life and be associated with an unnecessary burden to the health care system. The universal Israeli health care system enables the administration of radiotherapy without financial or regulatory barriers, even at EOL. We aimed to assess the use radiotherapy towards EOL in a tertiary care Israeli cancer center. Methods: We retrospectively analyzed data of patients receiving palliative radiation and died within 30 days of their simulation from March 2019 until September 2020. Results: Out of approximately 2,000 patients treated with radiotherapy during the study period, 148 (8%) patients were referred for palliative radiation and died within 30 days of their simulation. The majority (88, 59.5%) were male, the median age was 67.3 years and the most common malignancies patients suffered from were lung cancer (49, 33.1%), gastrointestinal tumors (28, 18.9%), genito-urinary malignancies (23, 15.5%) or breast cancer (15, 10.1%). The median ECOG PS was 3. Nineteen patients (12.8%) did not initiate radiation treatment plan, 24 patients (16.2%) completed less than half of the planned treatment and 89 patients (60.1%) completed the entire duration of treatment. Of the patients who completed the planned therapy, 34 patients (38.2%) received a single fraction protocol. The majority of patients (89, 60.1%) were referred to the radiation unit by their treating medical oncologists or hemato-oncologist. None of the patients were referred by palliative care team members at our center. Most (105, 70.9%) received previous systemic therapies; but less than half (48, 45.7%) were under active treatments within a month prior to the radiation simulation. Conclusions: Relatively large number of patients with advanced malignancies are referred for futile palliative radiotherapy during the last 30 days of their life, thus impairing their quality of life and creating an unnecessary burden on public health services. These patients are often being referred by their treating oncologists who are familiar with their oncological history. These findings call for the implementation of collaborative multi-disciplinary teams, primarily directed at optimizing care at the end of life, setting achievable treatment goals, and improving quality of life.

scholarly journals Comparative Effects of Iron Chelators on the Transfusion-Dependent Beta-Thalassemia Patients

2018 ◽  
Vol 26 ◽  
pp. 14-19
Author(s):  
Muhammad Mahbub Ul Alam ◽  
M Alauddin ◽  
M Jollilur Rahman ◽  
Rawshan Akhter ◽  
Chinmoy Kanti Das
Keyword(s):  
Quality Of Life ◽  
Iron Chelation ◽  
Self Esteem ◽  
Physical Component Summary Score ◽  
Summary Score ◽  
Beta Thalassemia ◽  
Adherence To Treatment ◽  
Treatment Rate ◽  
Group I

This prospective study assessed the quality of life of patients with transfusion-dependent beta-thalassemia receiving three different iron chelation treatments. Patients enrolled were receiving one of the following chelation therapies: Group-I: deferoxamine (n=21), Group-II: deferasirox (n=75) and Group-III: deferoxamine in combination with deferiprone (n=39). The three groups were compared in terms of their quality of life, satisfaction and adherence to treatment, control of their health, and self-esteem through the completion of five questionnaires. A higher percentage of patients receiving deferoxamine felt that their treatment negatively influenced their body and skin appearance and limited their ability to work, attend school, and perform daily tasks (P=.0.0066). The adherence to treatment rate and self-esteem were the lowest in the deferoxamine group (P<0.05). The deferoxamine group also had the lowest physical component summary score in the SF-36 questionnaire (P=0.014). This study suggests that the quality of life of beta-thalassemia patients receiving chelation therapy is dependent on the type of iron chelation treatment they receive. The study provides insight into important factors associated with the quality of life of these patients, which are essential for developing a more suitable clinical support team and counseling in order to maximize the treatment benefits for these patients in daily clinical practice.TAJ 2013; 26: 14-19

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