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Haematological Malignancies
Table 1: Incidence of Cardiac Events over a Three-year Period
Myocardial accumulation of iron has not yet been extensively studied in
Among 705 patients with Myelodysplastic Syndrome in the
patients with MDS. The results that have been obtained are
US Medicare Population
contradictory. Recent myocardial T2* magnetic resonance imaging (MRI)
studies suggested that iron-loading of the heart can occur after 75–100
Number of Patients (%)
Any cardiac-related event 522 (74)
units of blood have been transfused.
22
The value of T2* is only modified
Myocardial infarction 142 (29)
by iron overload independent of coronary disease. Two recent studies
Congestive heart failure 344 (48) using T2* MRI failed to show an iron accumulation in the hearts of
Arrhythmias 374 (53)
patients with MDS after 63–90 units of blood. Iron accumulation in the
Other cardiac events 415 (58)
liver was shown in all of the patients studied.
23,24
A recent report from an
Data from Goldberg et al., 2007.
19
Italian group study confirms the relationship between cardiac overload
Table 2: Eligibility Criteria for Iron Chelation Therapy in and transfusion burden (of more than 100 blood units).
25
It was a short
Patients with Myelodysplastic Syndrome, According to the
and heterogeneous series (some patients received chelation therapy,
Nagasaki Consensus Statement
32
others did not), which may have contributed to the findings. Increased
Transfusion Dependency
NTBI in patients with MDS may cause direct myocardial tissue damage.
Serum ferritin level >1,000–2,000µg/litre or other evidence of significant tissue
This cannot always be shown by MRI, which visualises iron storage.
26
It
iron overload has been suggested that there may be a long latency period between iron
Patients with low-risk MDS
accumulation in the liver and iron overload in the hearts of patients with
*IPSS low or intermediate-1 category
MDS.
15
This is supported by a more recent T2* MRI series.
27
*WHO-type refractory anaemia (RA), RA with ringed sideroblasts (RARS)
and 5q- syndrome
Outcomes of Chelation Therapy in
Documented stable disease
No co-morbidities that severely limit prognosis
Myelodysplastic Syndrome
Candidates for allografting
The positive impact of iron chelation therapy on survival has been clearly
shown in patients with β-thalassaemia major, in whom maintenance of
Data from 374 patients with MDS show that once patients with MDS serum ferritin levels below 2,500µg/l was the major determinant of cardiac
develop a need for regular transfusions, their probability of survival disease-free survival.
28
Although there are few studies of the efficacy of
decreases (hazard ratio for death 1/58 with a probability of 0.005).
6
In a iron chelation therapy in patients with MDS, evidence is slowly
survey of 467 patients with MDS followed from diagnosis to death or accumulating that efficient iron chelation could have a positive impact on
progression to leukaemia, 51% of non-leukaemic deaths were due to survival in patients with MDS.
cardiac failure and 8% were due to hepatic cirrhosis. Other related
complications of MDS leading to death include haemorrhage and A retrospective study on 178 patients with MDS indicated that iron
infection.
3
Cardiac failure was a significantly more common cause of chelation therapy was significantly associated with improved survival in
death among MDS patients who were transfusion-dependent than patients with low- or intermediate-1-risk MDS.
29
The median overall
among those not receiving regular transfusions. Iron overload was a survival rate was not reached at 160 months in patients who received
major contributor to this increased mortality. iron chelation therapy. It was only 40 months in those who did not
receive iron chelation. Significantly more patients who received iron
In a retrospective Japanese study of 292 patients with MDS and other chelation therapy survived up to four years (80 versus 44%; p<0.03).
transfusion-dependent anaemias, cardiac and hepatic dysfunction were Serum ferritin levels fell significantly in patients who received iron
present in 21.9 and 84.6% of patients studied, respectively.
19
Among the chelation therapy, and increased significantly in those who did not. In
patients who died, 24.0% had cardiac failure, 6.7% had hepatic failure and another retrospective study in 292 patients with MDS or other
97% of those who died had serum ferritin levels above 1,000µg/l. transfusion-dependent anaemias, effective iron chelation therapy with
deferoxamine (daily or continuous chelation therapy) resulted in
In a large retrospective study of 840 consecutive patients with MDS, heart improved levels of serum ferritin, liver enzymes and fasting blood
failure (28 versus 18%; p=0.001) and cardiac death (69 versus 55%; sugar levels.
19
Intermittent deferoxamine therapy conferred no benefit.
p=0.03) were significantly more common in transfusion-dependent than in
non-transfusion-dependent patients.
20
In a Cox analysis with time- These retrospective findings need to be confirmed by prospective studies. In
dependent co-variates, the risk of non-leukaemic death (hazard ratio 2/12; a prospective cohort study that enrolled 170 patients (five of whom were
p<0.001), heart failure (hazard ratio 1/34; p=0.03) and cardiac death lost to follow-up) with MDS receiving regular blood transfusions, iron
(hazard ratio 2/99; p=0.01) were all increased in transfusion-dependent chelation therapy significantly improved the median overall survival further
patients. The development of secondary iron overload significantly increased to diagnosis from 51 to 115 months (p<0.0001).
30
After adjustment for
the risk of non-leukaemic death (hazard ratio 1/15; p<0.001) and specifically other prognostic factors, such as sex, age, IPSS category and transfusion
increased the risk of developing heart failure (hazard ratio 1/17; p< 0.001). requirement, the survival difference remained significant. The main
prognostic factor of survival in Cox analysis is correct iron chelation. Most
Transfusion dependency may be a reliable indicator of the evolution of the importantly the difference of survival is due to non-leukaemic death.
disease. It must be recognised that the limited survival of patients with MDS
may be, at least partly, caused by a deterioration of their stem cell disorder Eligibility for Iron Chelation Therapy
(for example the progression of MDS to AML) and the presence of Current guidelines for the management of iron chelation therapy in
co-morbidities.
21
This is in addition to the direct effect of iron overload as a patients with MDS are based on non-randomised trials, expert opinion
result of blood transfusions. and the experience of iron chelation in patients with β-thalassaemia
76 EUROPEAN HAEMATOLOGY
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