Survival and causes of death in 2,033 patients with non-transfusion-dependent β-thalassemia

Musallam, Khaled M.; Vitrano, Angela; Meloni, Antonella; Pollina, Sebastiano Addario; Karimi, Mehran; El‐Beshlawy, Amal; Hajipour, Mahmoud; Marco, V. Di; Ansari, Saqib Hussain; Filosa, Aldo; Ricchi, Paolo; Ceci, Adriana; Daar, Shahina; Vlachaki, Efthymia; Singer, Sylvia T.; Naserullah, Zaki A.; Pepe, Alessia; Scondotto, Salvatore; Dardanoni, Gabriella; Bonifazi, Fedele; Sankaran, Vijay G.; Vichinsky, Elliott; Taher, Alì; Maggio, Aurelio

doi:10.3324/haematol.2021.278684

Cited by 28 publications

(28 citation statements)

References 14 publications

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“…The IHR database includes all β-thalassemia patients who have attended participating centers from January 1, 1997 onward. We analyzed data from all patients with NTDT (defined as previously described 8 ) who had not transitioned to regular transfusion programs and who had documented hemoglobin and serum ferritin levels.…”

Section: Risk Of Mortality From Anemia and Iron Overload In Nontransf...mentioning

confidence: 99%

“…Our work is limited by our ability to only analyze a subset of patients with documented hemoglobin and serum ferritin levels, which could have introduced a selection bias for patients with severe disease requiring regular follow-up, as is also evident from a higher and earlier mortality in this subset of patients compared to our overall cohort. 8 Prospective studies are merited in such context, as they could also assess the E78 CORRESPONDENCE effects of longitudinal variations over time and not only spot measurements which may not be ideally representative. The risks of mortality from low hemoglobin and high serum ferritin levels seem to be additive, which suggests a need to address both factors with prompt and comprehensive conventional management.…”

Section: Risk Of Mortality From Anemia and Iron Overload In Nontransf...mentioning

confidence: 99%

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Risk of mortality from anemia and iron overload in nontransfusion‐dependent β‐thalassemia

Musallam¹,

Vitrano

Meloni

et al. 2021

American J Hematol

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Section: Risk Of Mortality From Anemia and Iron Overload In Nontransf...mentioning

confidence: 99%

Section: Risk Of Mortality From Anemia and Iron Overload In Nontransf...mentioning

confidence: 99%

Risk of mortality from anemia and iron overload in nontransfusion‐dependent β‐thalassemia

Musallam¹,

Vitrano

Meloni

et al. 2021

American J Hematol

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“…There are currently no approved agents for the management of anemia in NTDT 11 . Transfusions are used in settings of expected drop in Hb such as pregnancy, infection or surgery; and some physicians also elect to use short courses of regular transfusions to promote growth in childhood or prevent/treat morbidity in adulthood in view of evidence of benefit from observational studies 12–14 . Even in the absence of transfusions, NTDT patients remain at risk of iron overload secondary to ineffective erythropoiesis, low hepcidin levels, and increased intestinal iron absorption 1 .…”

Section: Introductionmentioning

confidence: 99%

“…11 Transfusions are used in settings of expected drop in Hb such as pregnancy, infection or surgery; and some physicians also elect to use short courses of regular transfusions to promote growth in childhood or prevent/treat morbidity in adulthood in view of evidence of benefit from observational studies. [12][13][14] Even in the absence of transfusions, NTDT Khaled M. Musallam and Rayan Bou-Fakhredin contributed equally as first authors.…”

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confidence: 99%

2021 update on clinical trials in β‐thalassemia

Musallam¹,

Bou‐Fakhredin

Cappellini

et al. 2021

American J Hematol

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The treatment landscape for patients with β-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusiondependent β-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost.Patients with non-transfusion-dependent β-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation. | INTRODUCTIONThe β-thalassemias are a group of inherited disorders of hemoglobin (Hb) synthesis characterized by chronic anemia of varying severity.The degree of anemia relies on several genetic and environmental factors and determines the need for regular transfusion therapy. It is now common practice to classify patients as having transfusion-The TDT patients (β-thalassemia major and severe forms of HbE/β-thalassemia) are those who commonly present in early childhood with severe anemia and require lifelong transfusion therapy for survival. 1 Although the introduction of transfusions improved survival in TDT patients, it did not come without its own side-effect, systemic iron overload leading to end-organ damage and increased mortality from cardiac or hepatic disease. [2][3][4] Advances in iron chelation therapy and the introduction of MRI techniques to detect organ-specific iron overload have led to improved management and patient outcomes. 5,6 Still, TDT comes with considerable burden to the patient, clinician, and overall healthcare system owing to persistent morbidity and high healthcare utilization, poor access to optimal care and high treatment cost especially in resource-limited countries, and several unmet needs in terms of efficacy, safety and adherence to conventional therapies. 7 Allogeneic hematopoietic stem-cell transplantation (HSCT) has been used successfully for the past few decades to offer curative therapy for patients with TDT, but is only available to a minority of patients with compatible donors. 1 Patients with NTDT (β-thalassemia intermedia and mildmoderate forms of HbE/β-thalassemia) usually present later in childhood or even in adolescence with mild-moderate anemia that does not require immediate placement on a regular transfusion program. 1,8 Progress made over the past few decades has indicated that the diagnosis of NTDT carries greater morbidity than previously recognized.Ineffective erythropoiesis and anemia have been linked to an array of morbidities stemming from chronic hypoxia and an established hypercoagulable state. 1 Patients with Hb levels < 10 g/dl are at an increased risk of morbidity development, and variations of 1 g/dl can change a patient's morbidity risk. 9,10 There are currently no approved agents for the management of anem...

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“…To our knowledge, this is the first longitudinal analysis of survival, and factors influencing survival, in people with haemoglobin E thalassaemia, the most common form of severe β-thalassaemia worldwide. Survival in patients with haemoglobin E thalassaemia was shorter than that in people with other forms of thalassaemia 15 , 16 or in individuals without thalassaemia in Sri Lanka 17 (cumulative survival by age 50 years was estimated as 93·4% in a large cohort of patients with thalassaemia intermedia; 16 life expectancy in Sri Lanka at birth is estimated at 76·98 years). 17 Deaths and clinical complications were related to both chronic anaemia and iron overload.…”

Section: Discussionmentioning

confidence: 92%

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study

Premawardhena

Ediriweera

Sabouhanian

et al. 2022

The Lancet Global Health

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Background Worldwide, haemoglobin E β-thalassaemia is the most common genotype of severe β-thalassaemia. The paucity of long-term data for this form of thalassaemia makes evidence-based management challenging. We did a long-term observational study to define factors associated with survival and complications in patients with haemoglobin E thalassaemia. MethodsIn this prospective, longitudinal cohort study, we included all patients with haemoglobin E thalassaemia who attended the National Thalassaemia Centre in Kurunegala, Sri Lanka, between Jan 1, 1997, and Dec 31, 2001. Patients were assessed up to three times a year. Approaches to blood transfusions, splenectomy, and chelation therapy shifted during this period. Survival rates between groups were evaluated using Kaplan-Meier survival function estimate curves and Cox proportional hazards models were used to identify risk factors for mortality. Findings 109 patients (54 [50%] male; 55 [50%] female) were recruited and followed up for a median of 18 years (IQR 14-20). Median age at recruitment was 13 years (range 8-21). 32 (29%) patients died during follow-up. Median survival in all patients was 49 years (95% CI 45-not reached). Median survival was worse among male patients (hazard ratio [HR] 2•51, 95% CI 1•16-5•43), patients with a history of serious infections (adjusted HR 8•49, 2•90-24•84), and those with higher estimated body iron burdens as estimated by serum ferritin concentration (adjusted HR 1•03, 1•01-1•06 per 100 units). Splenectomy, while not associated with statistically significant increases in the risks of death or serious infections, ultimately did not eliminate a requirement for scheduled transfusions in 42 (58%) of 73 patients. Haemoglobin concentration less than or equal to 4•5 g/dL (vs concentration >4•5 g/dL), serum ferritin concentration more than 1300 µg/L (vs concentration ≤1300 µg/L), and liver iron concentration more than 5 mg/g dry weight of liver (vs concentration ≤5 mg/g) were associated with poorer survival.Interpretation Patients with haemoglobin E thalassaemia often had complications and shortened survival compared with that reported in high-resource countries for thalassaemia major and for thalassaemia intermedia not involving an allele for haemoglobin E. Approaches to management in this disorder remain uncertain and prospective studies should evaluate if altered transfusion regimens, with improved control of body iron, can improve survival.

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Survival and causes of death in 2,033 patients with non-transfusion-dependent β-thalassemia

Cited by 28 publications

References 14 publications

Risk of mortality from anemia and iron overload in nontransfusion‐dependent β‐thalassemia

Risk of mortality from anemia and iron overload in nontransfusion‐dependent β‐thalassemia

2021 update on clinical trials in β‐thalassemia

Survival and complications in patients with haemoglobin E thalassaemia in Sri Lanka: a prospective, longitudinal cohort study

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