Survival Comparability Between Thalassemia Major Versus Thalassemia Intermedia

Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood  for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described.

Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM  versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015.

Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) .  The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p-value<0.0001; Figure 1A). Survival was higher for TI subjects (median age was 73.6 years). Cox regression models of TM versus TI suggested that risk of death for TM patients was 6.8 times higher than TI patients (HR 6.8 (3.3), p-value<0.0001). However, the introduction of chelation treatment (DFO, 1965), changed the Kaplan-Meier curves showing that there was not statistically significant difference between TM versus TI patients in life expectancy ( log-rank test, p-value=0.086; Fig. 1B).

Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one’s.  Moreover, the TM risk of death has been decreased from 6.8 to  2.8 (Cox Model HR 2.8 (1.7), p-value=0.099).

These findings, if further confirmed, suggest as, in Western countries, our approach for  genetic counselling of  “at risk couples” for TM should be reconsidered.

Table 1.  Causes of death in Thalassemia Major and Thalassemia Intermedia patients.

 

	Diagnosis
Causes of Death	TM n (%)	TI n (%)
Cancer	3 (7,5)	5  (38,5)
Heart Damage	16 (40,0)	2 (15,4)
Infection	3 (7,5)	3 (23,1)
Multi Organ Failure	1 (2,5)	0 (0,0)
Stroke	1 (2,5)	0 (0,0)
Liver Failure	3  (7,5)	1 (7,7)
Not Available	11 (27,5)	1 (7,7)
Other complications not related to Thalassemia	2 (5,0)	1 (7,7)
Total	13	40

 

 

Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965).