Thalassemia Patients and Friends
Discussion Forums => Working Towards a Cure => Topic started by: Andy Battaglia on August 25, 2009, 04:56:13 AM
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From the Archives of Iranian Medicine, Volume 12, Number 3, May 2009 http://www.ams.ac.ir/AIM/09123/0013.pdf
Results
Forty-nine patients (28 women and 21 men)
enrolled in the study. The mean age of the patients
was 18.38 years (range: 10 – 40 years). The mean
packed red cell transfusions in one year before
starting of HU was 22.75 units, which decreased to
6.02 after treatment (P< 0.01, t-test). The mean Hb
levels was 8.52 g/dL and 8.45 g/dL during one
year before and after HU therapy, respectively; this
difference was not significant (P=0.543, t-test).
Before initiation of HU, the patients required blood
transfusion every three to four weeks, but only
three to four months after treatment, transfusion
stopped in 12 patients, spaced out in 32 patients
(once every three to four months instead of once
every month), and continued in five patients. The
mean ferritin level during one year before the
starting of HU was 2751.44 ng/mL, but decreased
to 1594.20 ng/mL after one year of HU therapy
(P<0.001, t-test). The mean deferoxamine injection
decreased from 84.83 to 49.46 (P<0.001, t-test)
(Table 1). We had only one hematologic
complication (platelet<100,000/mm3). Thrombocytopenia
was transient, which resolved with
discretion of HU dose. Eight patients suffered from
nausea at the beginning of treatment, which
resolved spontaneously. There were no hepatic,
renal, or other complications during the treatment.
Discussion
The mainstay of treatment in major β-
thalassemia still relies on regular blood
transfusions and the use of iron chelators.
Pharmacologic reactivation of γ-globin genes holds
great promise for the treatment of thalassemia
syndromes as well as of sickle cell disease.
Hydroxyurea has been demonstrated to up regulate
γ-chain synthesis and HbF production. This drug
has been used successfully in the treatment of
sickle cell anemia by increasing HbF levels and
reducing clinical complications,8 although there is
limited experience with this agent in betathalassemic
patients.9,10
We described the results of the treatment of 49
splenectomized, transfusion-dependent major betathalassemic
patients with HU. The effects on total
Hb, transfusion requirements, and the level of
ferritin were the most significant observation of
this study.
We observed a significant decrease in blood
transfusion. The response to HU was equal in
males and females. Decrease of transfusion
requirement began in the first three to four months
of HU therapy. Our findings show that the effects
of HU therapy can occur after a short period of
time.
The significant decrease of serum ferritin in the
responder group is clinically very important as iron
overload is the main hazard to these patients. The
serum ferritin decrement is due to decrease of
blood transfusion and to a lesser extent due to
increased iron utilization by increased Hb
production and also suppression of ineffective
erythropoiesis.
HU treatment was well-tolerated and it did not
cause any hematologic toxicity except in one
patient who developed transient thrombocytopenia
which resolved after a short period of HU
cessation.
Although the carcinogenic effect of long-term
use of HU remains a matter of serious concern, we
did not encounter any malignancies including
leukemia in the five-year follow-up. This study
shows that HU can be an effective and safe
treatment for major thalassemia in long-term
therapy.
This corroborates the report from several years ago from Algeria that showed positive results using hydroxyurea in thal majors. This was a bigger study and the positive results suggest that hydroxyurea therapy should be considered one of the tools in decreasing transfusion frequency in thalassemia major. The lack of serious side effects is also quite encouraging.
The report is attached to this post as a pdf file.
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Thank you Andy so much for the wonderful post
I just want to add two more points concerning the Iranian studies.
In Syria conference, another Iranian study was also discussed in one of the lectures but that one measured the carcinogenic effect of the hydroxyurea on patients after 10 years fo usage and also found it to be safe except for one patient that got leukimia but it was not proved to be directly related to the treatment (there are many other variables and further studies were recommended)
According to the study, it was found that the most effective and safe dose is between 10 to 20mg per kilo
Half the patients enrolled in the study were transfusion independant after the usage of HU, but Professor Cappilini (Italy) commented that from her expierence this has to do with the nature of the Iranian mutation in this certain population. From her expierence, less results were achieved in other populations.
I will post this study too if i find it online
manal
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Keep in mind that the Algerian study was also done with majors and was successful. I think there is much potential for hydroxyurea and other fetal hemoglobin inducing drugs, to reduce the transfusion needs of majors, which in turn will reduce the amount of transfusion related problems, including the amount of iron taken in. As positive as this report is, I do expect much more from Dr Perrine's work with short chain fatty acid drugs, which should prove to be even safer over long term in addition to having a more dramatic effect on hemoglobin levels. Eventually, this will cause great changes in the approach to treatment of thalassemia.
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Thanks for the post Andy.
Its nice to know that my dr is doing a great job. hehehe
I have been on Hydroxyurea for over 8+ years.
Most time my hb is @ 99 after 6 weeks so thats pretty good. :biggrin
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8 years is a pretty long time,just curious,you never had any side effects?
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Thanks for posting this Andy,
I hope that patients continue to have good results with fetal hg inducers. I cannot wait to hear Dr. Perrine talk about her work in NY. As the clinical trials started in April/09 I wonder if some preliminary results may be available by October.
Zaini, I have high hopes that a hg inducer will work very well for lil Z - especially hemaquest.
Cherieann, I am glad to see that it is working well for you:)
Sharmin
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Sharmin,
Thanks a lot,i have a few concerns regarding Hydrea,and naturally i am scared of trying something new which might effect Lil Z's growth,so we'll wait for a better form of hb inducer,i am not saying Hydrea isn't good,its working really well for Cherianne,6 weeks of interval at her age is awesome :) .
Zaini.
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Thanks Zaini. Yes it is doing well for me.
I haven't noticed any side effects and my haematologist keeps a close eye on my levels.
Maybe thats why I'm doing well, they are monitoring well? :hugfriend
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Hi All ,
it will b good for me to try this or i should have to avoid trying any drug like this ??? wat do you say ?? i wana try this and a few times talked abt it to my doc as well , but she wn't to try any drug ( i m using try to bcoze she said that its not proven yet on thal majors ad I wouldn't like to experiment it on you ).... i have forward this study (mentioned above ) to my doc and wil ask her again that if it is safe then i m ready to try ,( i dont know why i m always stay ready to try for anything that seems to b beneficial HAHAHA) .... wat u people think ?? is it safe ?/?? and does it looks safe in my case ???
Regards
Umair
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Life is always filled with risks even after it has been proven because no individual is exactly the same. We all react differently. You need to make the decision for yourself.
I recommend your Drs advice for being careful but at the end of the day, your Dr gets to take a break from dealing with Thal where as you will never be able to walk away.
My advice... go with your instinct.
For me, I take my Drs advice or warnings as she explains things but I have the overall choice of whether to trial or not. In NZ I have no one to compare to so I am my own guinea pig.
Now that I have you all, I have more people to get info from before I make choices. hehe
The plus is also I talk aboutwhat you guys are taking and together we choose whether I should trial it as well.
Umair... follow your instinct.
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Cheriean ,
yeah i know that final decisin will be mine , as it was in interferon's case ... i want to try everything that is available here and sound promising .. i m a lil tired of going for Tx every 10-12 day .. and i dont like to go there that's why i m late to my scheduled Tx date .... i dont know why i dont like to go there , admin of my tal center has told me that when-ever i want i can go there fr Tx and they will arrange blood for me when-ever i will b ther for blood .. and he has said me to dont worry abt shortage just plan ur Tx day and u will get blood at that day but i still dont like to go there ... that's the reason why i want to try this ...
i think , i should ask my doctor again abt it .. hope to hear sumthing positive. i think my doc will allow me to go for this ..
Umair
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Umair,
There is nothing wrong with feeling that you dont want to go for a transfusion, as long as you still keep the transfusions up. We all need you with us.
I do understand though because I am exactly the same. As much as I love my hospital family, I hate going in. I have always felt that its one day stuck in a place when I want to be else where. One day of my life that I will never get back. But I also remember that I have to give up that one day or else...... :dunno Don't want the alternative. I guess that is why I go all out trying to extend the transfusion times and communicate with my specialist. I refuse to discuss with the junior drs now because they mess things up.
I control my destiny :biggrin
Chin up my mate, you will find your silver lining in life. :hugfriend
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Cherianne,
I really love your positive attitude and your encouragement for everyone :hugfriend.
Umair,
Now that your ferritin is quite low your body must be a bit relieved,so you can ask your doctor if she allows you a little dose of Hydrea after doing all the necessary tests,and then keep monitoring all the blood levels.
Zaini.
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Thanks Zaini,
I learnt from the best. :wink
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I don't know guys. Cherieann's case is one of the few cases I have heard of, concerning hydro's success. Here it has been tested but the results were not so encouraging.
Lena.
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Everybody is different so we react different. I did a trial and after 4 months, started extending transfusions. As my doctor said, it reacts differently. Some need a higher dose where some don't. Some will take time where other people, it won't work on.
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Of course, everyone is a specific individual case. I only refer to the results I am aware of.
Lena.
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As Manal has previously pointed out, hydroxyurea does work better in people with certain genetic mutations, so this is one of the factors that affects the results.
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hi andy
and witch mutation u mean?
u think i could give em a chance to risk it.....?
i have thebeta compound pluse the alpha trail...
panos
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Panos,
Two thalassemia mutations that have been shown to have a better response to hydroxyurea are Xmn1 and IVSII-1. It has also been found that alpha deletions can add to the effect in these beta mutations. Do you know which beta mutations you have?
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hi
i have posatet my mutation in an earlyer post
look here:
first tx for ur reply manal.
now i give u the results of my analysis.
compound heterozygotie ß°ß+(OMIM:141900;ICD-10:D56.1)
BUT......!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
not only this one......
there is an other mutation too in my genes
heterozygote α+-Thalassämie(-α+/αα) (OMIM:141800;ICD-10.D56.0)
so i have a triple mutation in my genes witch is pretty rare.....
the positiv point of view is....that the 3rd mutation seemed to be
helpfully and made the thal milder.......
andy could u tell us somethink about it? panos
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okiey
that mean's there is no chance that i can try hydrea , bcoze i dont know which mutation i carry's ... anywayz, thank u al , for helping me to decide .
lots of Regards
Umair
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Panos,
This is very difficult to answer. Studies have shown that hydroxyurea increases hemoglobin levels in thalassemics with many different mutations. However, we know that it has not been effective in all patients who have used it. Some of this is related to less than 100% compliance by the patients, so it it difficult to say whether it was lack of compliance or if it just didn't work well for them.
Using hydroxyurea in thal majors to reduce the frequency of transfusions is a relatively new idea, as opposed to the concept of completely eliminating transfusions. It is believed that this increases fetal hemoglobin and also reduces ineffective erythropoiesis (production of young red cells), which also affects the severity of thalassemia. Fewer ineffective red cells does make for a healthier individual.
Hydroxyurea also has the effect of shrinking masses caused by extramedullary haemotopoiesis, where red cells grow outside the bone marrow. This often creates serious problems as these masses can press against organs, causing pain and reducing function of the organs. Panos, because of your history, I am wondering if hydroxyurea has ever been suggested as a way of shrinking the extramedullary growths. Hydroxyurea may have a positive effect for you in more than one way. I would suggest you talk to your doctor about this and see if it seems practical for you.
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Umair,
I agree to Andy's suggestion to talk to your doctor to try Hydrauxyurea. My daughter is taking it for last 3yrs and it is helping her to reduce the frequency. Earlier she used to get transfused every 30 days but now it has increased to 45 days since last 3 yrs.
My daughter is taking 20mg/kg. I have not seen any side effect. If anybody needs any more info, I will be happy to share.
Regards,
Om
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http://journals.lww.com/jpho-online/Abstract/2007/11000/Efficacy_of_Hydroxyurea__HU__in_Reduction_of_Pack.5.aspx
Background: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta-thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major.
Method: Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control.
Result: Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P<0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients.
Conclusions: HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions.
Since the focus of study shifted from replacing transfusions entirely, which is unlikely to happen with hydroxyurea in thal majors, to reducing the amount of blood being taken, we are seeing very encouraging results. The problem with the earlier research was that majors were not allowed to transfuse during the hydroxy therapy. When hydroxy did not raise Hb enough to avoid transfusions, it was thought that hydroxyurea had no place in treatment of thal major, but once hydroxy was given to patients who did not stop transfusing, the value of hydroxyurea became evident. The frequency of transfusion and the amount of blood needed both dropped. As I mentioned, the reduction in ineffective erythropoiesis also plays a role. Fewer transfusions mean less iron and less of all the bad effects of iron. I really think many majors can benefit from hydroxyurea therapy.
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These are really encouraging results. As main concern of thal majors (and specially for me these days) is more blood requirements and decreasing tx gaps with age. I hope we can start soon on HU and get good results.
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Hi Opkaram,
i have forward the study to my doctor and .. yeah, i'll definitely ask my doc to my doctor to check if i can give it a try .. result of your daughter r really encouring as 15 day's increas in interval mean's alot for a thall maj .. i will definitely again talk to my doctor abt this .. i will contact you whenever i need ur help and thanx for offering help .. i will contact u if my doc told me to give it a try ....
@ Andy
Thanx ya Andy , for this sharing, its encouraging, ...
@ Tariq
Agree to you buddy , gap between Tx is most imp thing for us (thal maj ) and as u people red my previous posts , that depression was caused bcoze of the shortness of the gaps .. so, its really an important thing for us , from Iron overload aspects too ,,,
Best Regards
umair
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Hello Umair,
My advice to you is to give it a try (if the doctor agrees ) cause it might work for you cause not all mutations have been studied with the hydroxurea and even it could have different results with two persons with same mutation cause there areother factors in the body that can aid either positivly or negativly.
All you have to do is to check the kidney and liver functions every month until you are sure that it does not affect them and usually doctors give up to 9 months before they judge whether it works for the patient or not
manal
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where and in which places this therapy conducted for beta thalassemia major ,is their any place in india
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Hi Manal Sis,
i m looking to talk about this to my doctor in my next visit, let's see when i will go to visit next .. my last vist was a few months back mayb in MAY or June ... looking to go again soon .. i will talk to her about this again , i have forward this study to her ... i m hopeful that she will agree to give it a try ..... 9 months wooooo, long time but its okiey .. hope that it will b helpful to increase the intervalls ... thanx ya Sis for taking time to reply, and Welcome ack :) ....
Best Regards
Umair
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ruchi
This is a drug that has to be prescribed by the doctor and it is sold everywhere including India
Umair
You are welcomed my friend and good luck
manal