The era of comparable life expectancy between thalassaemia major and intermedia: Is it time to revisit the major‐intermedia dichotomy?

Abstract

SummaryIn the last few decades, the life expectancy of regularly transfused b-thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with b-thalassaemia intermedia (TI) remains unknown. Three hundred and seventy-nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan-Meir curves showed statistically significant differences in TM and TI survival (P < 0Á0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0Á086), reducing the Hazard Ratio of death in TM compared to TI from 6Á8 [95% confidence interval (CI) 2Á6-17Á5] before 1965 to 2Á8 (95% CI 0Á8-9Á2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major-intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.

The new era of chelation treatments: effectiveness and safety of 10 different regimens for controlling iron overloading in thalassaemia major

“…The survival of TM patients has improved to levels that are comparable to thalassaemia intermedia (TI) patients (Vitrano et al, 2017). However, heart damage still remains the major cause of death (Vitrano et al, 2017), and this scenario can only be explained by 'compliance failure'.…”

A prospective analysis for prevalence of complications in Thai nontransfusion‐dependent Hb E/β‐thalassemia and α‐thalassemia (Hb H disease)

“…Several complications linked to chronic anemia and ineffective erythropoiesis including iron overload, endocrinopathies, especially diabetes mellitus (DM), extramedullary hematopoiesis (EMH), chronic leg ulcer, pulmonary hypertension (PHT), and thrombosis and so forth have long been observed in patients with thalassemia syndromes . Due to improving management of patients with TDT by regular blood transfusions and iron chelation therapy, these complications have decreased significantly in recent years . In contrary, a cohort study of TI patients has shown terrifying evidence that β‐TI patients representing NTDT had a much higher incidence of several thalassemia related complications compared to β‐TM who were well‐treated .…”

The effect of iron chelation therapy on overall survival in sickle cell disease and β‐thalassemia: A systematic review

“…A total of 18 individual papers describing 15 different studies were published between 2000 and 2017, and are summarized in Table . These studies included 7189 patients; however, some patients likely were counted more than once since the multicenter studies from Borgna‐Pignatti et al, although distinct, drew on the same patient populations in Italy .…”

“…These studies included 7189 patients; however, some patients likely were counted more than once since the multicenter studies from Borgna‐Pignatti et al, although distinct, drew on the same patient populations in Italy . A number of other multicenter studies were also conducted in Italy, and may also have included some of these same patients …”

“…Only 1 of the retrospective/longitudinal studies compared survival outcomes in β‐thalassemia patients according to the ICT received; a second study compared monotherapy to combination therapy . The remaining studies investigated survival outcomes according to various baseline and treatment characteristics: 1 investigated factors associated with death in a case‐control study; 4 studied outcomes according to compliance with or duration of ICT; 4 compared survival outcomes according to period of treatment (i.e., before or after availability of different iron chelation treatments); 1 measured survival in patients with thalassemia major and thalassemia intermedia before and after introduction of deferoxamine; and 1 measured rates of death in hepatitis C virus (HCV)‐infected and noninfected patients receiving ICT with deferoxamine …”