TIF Guidelines for the Management of Transfusion-Dependent β-Thalassemia

Abstract

The prospect of patients with transfusion-dependent β-thalassemia (TDT), once considered a fatal childhood disorder, has completely transformed over the past 50 years.¹ This is primarily attributed to the adoption of hemovigilance in transfusion therapy, the development of effective iron chelators, the validation of non-invasive tools for monitoring organ-specific iron loading, and the introduction of multidisciplinary care. Regrettably, access to these advances and optimal application of best practices remain largely confined to nations with robust economies, where comprehensive health and social care systems provide universal access to treatment.² Consequently, multimorbidity and shortened survival continue to burden patients in countries with limited resources, where most of TDT patients live.³ In high-income settings, improved survival of TDT did not come without its own “side effect,” where aging allowed several previously unrecognized morbidities to manifest, especially in patients who were exposed to the harmful effects of under- or sub-optimal treatment in the past.^{4, 5} Thus, the “gold standard” in TDT care is now fundamentally recognized as being a multidisciplinary approach to management, preferably in expert or reference centers, and with active engagement of patients and their families.⁶

Since its inception in 1986, the Thalassaemia International Federation (TIF) has remained committed to supporting patients/families and patient organizations, healthcare professionals, and policymakers to promote optimal care for patients with thalassemia and other hemoglobinopathies across the world. The preparation, publication, translation, and free distribution of management guidelines is a cornerstone of its educational mission. Widely recognized for their significant impact on the care of patients with TDT, and broadly endorsed by the international medical community, these guidelines serve as a critical resource for healthcare providers and a foundation upon which national policies and practices can be built.

The 5th edition of TIF “Guidelines for the Management of Transfusion-Dependent β-Thalassemia (TDT)” has now become available (available for free download at: https://thalassaemia.org.cy/tif-publications/).⁷ In keeping with the many and multiple unmet needs of patients in different geographies, the guidelines have been carefully crafted to offer evidence-based recommendations (key points and recommendations from select chapters on diagnosis and disease management are provided in Table 1, and a summary of monitoring recommendations is provided in Supporting Information S1: Table S1) while also suggesting solutions and pathways for care in resource-limited settings. Recommendations are provided by a global and diverse group of experts with decades of experience in patient care, through 17 interconnected chapters that echo the need of “true” multidisciplinary care throughout the patient journey from childhood to adulthood. The guidelines also include a chapter dedicated to the value of patient engagement, emphasizing the transformative power of patients as informed and effective advocates for their own needs. Additionally, patients have contributed to the review of various other chapters, ensuring that issues such as lifestyle and mental health are comprehensively addressed from the patients' perspective.

The advent of groundbreaking therapies for TDT in the past decade including curative gene therapy (insertion and editing) approaches as well as disease-modifying treatments approved for clinical use, have been met with great excitement and promise for a brighter future for patients worldwide. Dedicated chapters in the new guidelines present fundamentals of the design, development, and potential place in therapy for these novel agents, while also calling for further real-world evidence to address knowledge gaps. As previously stressed, the vast majority of patients are still unable to access such developments. This disparity highlights the urgent need to devise pragmatic and actionable solutions for countries, particularly those with high disease prevalence, to prioritize disease-specific policies for prevention and optimized care.

We strongly encourage healthcare professionals who follow these guidelines to advocate for their full adoption and implementation within their institutions and alert their national competent health authorities about their immense value. Evidence-based practices are vital for enabling early diagnosis and effective management, a basic human right of all patients, while at the same time contributing to safeguarding the sustainability of healthcare systems, which are greatly threatened consequent to immense geopolitical, economic, environmental, and public health crises.

All authors contributed to conceptualization and manuscript drafting or critical review.

K. M. M. reports consultancy fees from Novartis, Bristol Myers Squibb (Celgene Corp), Agios Pharmaceuticals, CRISPR Therapeutics, Vifor Pharma, Novo Nordisk, and Pharmacosmos; and research funding from Agios Pharmaceuticals and Pharmacosmos. M. D. C. reports consultancy fees from Novartis, Bristol Myers Squibb (Celgene Corp), Vifor Pharma, and Vertex Pharmaceuticals; and research funding from Novartis, Bristol Myers Squibb (Celgene Corp), La Jolla Pharmaceutical Company, Roche, Protagonist Therapeutics, and CRISPR Therapeutics. J. B. P. reports honoraria from Agios Pharmaceuticals, bluebird bio, Celgene (Bristol Myers Squibb), La Jolla Pharmaceuticals, Protagonism, Silence Therapeutics, and Vifor; and is a consultant for Agios Pharmaceuticals, bluebird bio, and Celgene (Bristol Myers Squibb). D. F. reports speaker honoraria, consultation fees, and/or grants from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Leo, Myocardial Solutions, and Roche. A. T. T. reports consultancy fees from Novo Nordisk, Bristol Myers Squibb (Celgene Corp), Agios Pharmaceuticals, Pharmacosmos, and Roche; and research funding from Novo Nordisk, Bristol Myers Squibb (Celgene Corp), Agios Pharmaceuticals, Pharmacosmos, and Roche. All competing interests are outside the present work. The remaining authors have no conflicts of interest to disclose.

Not applicable.