Kanjaksha Ghosh1 and Kinjalka Ghosh2
1 Surat Raktadan Kendra & research Centre, Gujrat , India
2 Clinical Biochemistry, KEM Hospital & Seth GS Medical College Mumbai, India
Corresponding
author: Kanjaksha Ghosh MD FRCP FRCPath. Surat Raktadan Kendra &
research Centre, Udhna Magdalla Road Surat 395002, Gujrat , India.
E-mail:
kanjakshaghosh@hotmail.com
Published: September 1, 2017
Received: July 5, 2017
ccepted: July 21 , 2017
Mediterr J Hematol Infect Dis 2017, 9(1): e2017055 DOI
10.4084/MJHID.2017.055
This article is available on PDF format at:
This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0),
which permits unrestricted use, distribution, and reproduction in any
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Dear Editor,
We read with interest the review article on iron chelation therapy in MDS patients[1]
in one of the recent issue of the journal. A recently similar article
has also been published suggesting that iron chelation may be helpful
in high-risk transfusion dependent MDS patients too.[2]
The effect of iron chelation therapy in low-risk MDS patient is
reasonably well established as it improves not only the quality of life
but also the survival as shown in Dusseldorf MDS registry study.[3]
In high-risk MDS iron chelation therapy was usually not considered
because of short survival, and, because of some of the complications of
chelation, likely in patients with hepatic dysfunction with short
survival, it was found to be not worth pursuing. However, since some of
the current drugs used for the purpose, e.g., decitabine &
azacitidine based therapy, have improved the survival of high-risk MDS
patients, so consideration of iron chelation therapy becomes apparent
also in these cases. However, this brings us to an important question,
i.e., Should all MDS patients even with minor iron overload with serum
ferritin above 500 ng/ml. receive iron chelation therapy, particularly
when efficient oral iron chelator is now available? To support this
idea Angelucci et al.[1] have in the paper under
discussion made significant observations. Our knowledge and experience
on iron chelation mainly emerge from our therapeutic practice of using
the same for transfusion dependent thalassemia patients. Here iron
deposition happens in bulk and chelation tends to remove the iron from
this bulk relatively inert as well as the extremely active labile and
non transferring bound free iron pool generating active, reactive
oxygen species (ROS). ROS is capable of mutagenesis by inducing double
stranded DNA break.[4] This mutagenesis can
theoretically help in the progression of a relatively benign form of
MDS to an aggressive one. Though this has not been directly proven it
was shown that patients with higher transfusion requirement and iron
overload also tend to evolve rapidly into leukemia.[5]
It
may be argued that patients with severe prognosis require more red cell
transfusions and then develop higher iron overload and having a rapid
evolution of MDS to more aggressive form naturally require more
transfusions, and thus, the evolution to leukemia has nothing to do
with iron overload. On the other hand, it may also be argued that
marked iron load, associated with a higher labile iron pool being toxic
to red cell progenitors[6,7] and by causing direct red cell membrane damage,[8] induces more frequent red cell transfusion and then more iron overload.
This iron overload brings about genomic instability,[4,8,9] mitochondrial damage and mutation in mitochondrial genome,[10,11] and by producing an unbalanced immune system, leads to rapid progression of MDS[12] to accelerated phase of leukemogenesis. If our second argument and Angelucci et al.[1]
argument are correct the iron accumulation even in a minimal amount in
crucial cellular compartments without necessarily producing massive
iron overload could be damaging and mutagenic. Thus, every patient with
MDS and even minimal iron overload should get adequate iron chelation
and efforts needs to be made to see whether such intervention alters
the natural history of the disease.
References
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Myelodysplastic Syndromes and Iron Chelation Therapy. Mediterr J
Hematol Infect Dis. 2017 Mar 1;9:e2017021. https://doi.org/10.4084/mjhid.2017.021
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