hydroxy urea in transfused patients

Hi
I think my son will be started on hydroxy urea after his next appointment on Wednesday. Any guidance on what to expect and what to look out for would be appreciated. Manal? Priya? or anyone else with experience.
From what I understood was that transfusions would have to be stopped so that there would be bone marrow activity earlier but now that they are using it in major also is that still applicable?
Wish us luck
Zahra

Zahra,

When you are under hydroxyurea, you should be monitering three things
1- The counts of white blood cells and hydroxurea should be stopped if they become below 3500
2- Kidney functions
3- Liver functions

These tests should be made monthly until you are sure that the body is tolerating the hydroxy then you start doing these tests every 3 months and then every 6 months

The good thing about hydroxy is that if for any reason there are side effects, they are completly reversed when the drug is stiooed

For some patients, they may feel dizzy, or had a stomach ache, i advise that the medicine is taken just before bed time

Hydroxy can be taken with or without food and even when you are on antibiotics

It is very safe taking the dose from 10mg per kg until 20mg per kg, but in some sickle cell cases it is taken until 35mg per kilo

The exact dose should be fine tuned according to each patient, i mean that there is no exact dose some  react positivly at lower doses and other patints at higher ones so we have to make a trail and error

Also you should know that some patients react positivly from the first month others don't and may take more time, that is why it is agreed that you can take it up to one year until you can decide wheather it is useful or not

Hydroxy helps to reduce:
1-  Size of the spleen and therefore the body is able to redirect its energy to growth
2-  Decrease the retix count and therefore reduce risk of bone deformity
3- The activity of the child increase and the child ''somehow'' eats better
4- Reduces ferritin levels

Hydroxy is best taken with L-carnitine (5 days per week) and magnesium

When taken with transfusions, in some patients, it can increase gap between transfuions and in some cases can eliminate transfuions

Wish you all the luck and please keep us updated

manal

Dear Manal,
Aoa. Thank you sooooooooooo much for writing such a comprehensive answer. I hope it works and that we see results soon. I wish to ask how much L-carnitine would be advised for a 13 kg two year old? Also is the magnesium in osteocare sufficient or is extra required? I hope he doesnt get more stomachache. We are still hoping the one caused by exjade will go away with time.
Thank you for your wishes. I will keep you informed inshallah.
Zahra

Zahra,

Best of luck with Hydrea .

Zaini.

Good luck Zahra.  Please keep us posted. 

Sharmin

You are welcome Zahra

As for L-carnitine it is taken from 50mg to 100 mg per kilo. But all studiies made concerning the usage of L-carnitine with thal were on the basis of 50mg per kilo. So according to your son's weight, he will be taking 650mg per day divided into 2 or three doses ( 5 days in a week)

As for magnesium, i think what is in Osteocare is fine. In addition that most multivitamin already contain magnesium

Manal

Dear Manal and Sharmin,
The doctor did prescribe the hydroxy urea but I havent gotten it yet. As expected he said that it isnt really possible to tell who it will help but they do have 9 patients who have become transfusion independant . Two of these have needed spleenectomies but he said not to worry about that as my son is too young at the moment. 
On the other hand some patients dont respond at all . Like they had been given a placebo. The dose we will start at is 20mg/kg . He  said at this dose we dont see the side effects seen when it is used as a chemo. No fertility issues, no nausea, vomiting , hairloss, etc. Some patients do have  a drop in white blood cell counts but usually it is controlled by lowering the dose or you could stop the medicine also to control it but he hasnt needed to do that i n any patient yet. Also kidney and liver functions willl be watched.
The target Hb is now 8.5. Lower than that and it will be back to transfusions. Initially they hope to space out transfusions. Like the next appointment is in 4 weeks but if Hb is around 10 they will not transfuse but wait another week. If its still above 9 wait another week and see how it goes. when it is below 8.5 they will transfuse.
I asked .how to know if wbc's are down. He said they will be watching it at appointments but if low there will be an infection and fever also.
Zahra

Hi,
I asked the doctor about L-carnitine but he said they tried it and found it didnt really help unless the patient had cardiomyeopathy ( I hope I got that right) .  I asked about the NO involved in the mechanism somehow being made more available by taking L-carnitine. He said that that mechanism is more in sickle cell patients where the disease is controlled by fetal Hb preventing the sickling . In thalassemia its a different mechanism. Something about younger RBC's being released by the bone marrow into the blood stream so that they have a longer life span. He said thalasemia patients already have only fetal Hb.
Can anyone explain this to me. I'm pretty confused.
Zahra

Hi Zahra,

I don't agree with your doctor aout the usage of L-carnitine, because  you will find below studies showing the importance of using l-carnitine in thalassemia both on protective/treatment levels and you can print them and show them to him. In addition that there are no side effects from using it

All the studies are published in scientific journals.

Improvement of Cardiac Function in Thalassemia major Treated with L-Carnitine
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=76522&Ausgabe=229926&ProduktNr=223829

Assessment of Puberty in Relation to L-carnitine and Hormonal Replacement Therapy in {beta}-thalassemic Patients.
http://lib.bioinfo.pl/auth:El%20Beshlawy,A

Apoptosis in Thalassemia major Reduced by a Butyrate Derivative
http://content.karger.com/ProdukteDB/produkte.asp?Doi=87890


Diastolic Dysfunction and Pulmonary Hypertension in Sickle Cell Anemia: Is There a Role for L-Carnitine Treatment?
http://content.karger.com/ProdukteDB/produkte.asp?Doi=89472

Pulmonary hypertension in beta-thalassemia major and the role of L-carnitine therapy.
http://www.ncbi.nlm.nih.gov/pubmed/19065439?dopt=Abstract

 
L-carnitine is generally a safe substance that is found in every cell in our bodies, you can even find it in baby food like in this link
 
..........L-Carnitine, Taurine, Ascorbic Acid, Lo Han Extract, Vitamin D, Stevia Extract, Rutin, Vitamin K, d-alpha -tocopherolsuccinate, SunActive FE ® Iron as Ferrous Pyrophosphate, Niacinamide, Vitamin B5, Boron Chelate, Magnesium Chelate, Vitamin B6, Copper Chelate, Vitamin B2, Vitamin B1, Vitamin B12 as........
http://www.babyorganic.com/cart.php?target=product&product_id=16190&category_id=249

So this means it is safe



Actually i don't get what the doctor explained to you. But in some other post, i explained the relation between fetal HB and hydrea, you will find it below, may be things would be clearer after you read it

http://www.thalassemiapatientsandfriends.com/index.php?action=profile;u=280;sa=showPosts;start=45

Concerning Hb f and its relation to thal or hydroxyurea, you will find below an explanation for this. First F HB refers to Fetal HB and it is one of the kinds of HB. When we were babies inside the wombs of our mothers, all our HB was Fetal Hb and is produced by the gamma genes and after the baby is delivered this F HB is still being produced until the baby is  around 6 months old. From 6 months to 12 months, babies are supposed to start producing Adult Hemoglobin (HB A) which is produced from the combination of both alpha and beta chains. At the same time the gamma genes which produce the HB F start to switch off as Adult HB is enough and it is needed more by the body.  Therefore by the age of maximum 2 years you will not detect the presence of HB F in the human body cause the body has replaced it with the adult HB. So this is the normal cycle for any person.
 
In thalassemia patients, the story is different because the body can not produce adult HB (because there are no beta chains to combine with the alpha chains to produce the Adult HB). At this point,  the body wants to defend itself and want to help itself so the body ''remembers''that one day it had gamma genes that produced HB F, so the body starts switching on the gamma genes to produce this fetal HB to help the body to survive. That is how thal is diagnosed by the presence of HB F. Because in people that don't have thal, there is 0% of Fetal HB but in thal patients Fetal Hb is present and the test that diagnose it is called blood electrophoresis test OR HPLC. These tests detect the presence of every kind of HB in the body and its percentage in the blood.
 
Again in order to produce adult HB you need 4 alpha genes and two beta genes. In Beta thalassemia the two beta genes are both muted and therefore can not produce the beta chains. What differentiate  thal major from thal intemedia? Both thal major and intermedia have two muted beta genes but the difference is that, in intermedia the two muted genes are not severely muted so this means they still can produce ''little good hemoglobin'' that enables their bodies to function for a while without the need for transfusions ( that is why some thal intermedia  transfuse later in life because you had some ''good'' HB produced) While in major there is no Hb produced at all cause the genes are severly muted and that is why major starts transfusing when they are babies or they would die.
 
Role of hydroxy in intermedias:
 
Though it is used with cancer patients, it was found by coincidence that hydroxyurea switched on the gamma genes and this resulted in the increase of Fetal HB in patients so they started giving it in smaller amount s to thalassemia intermedia patients and found that it can help them (NOW it is also given to thal major to increase gaps beween transfusions and sometimes eliminate them)  It helped them by increasing the percentage of HB f and this resulted in the increase of the total HB and therefore eliminating transfusions. Humans can live, function and grow with Fetal HB. Although Adult HB is the best choice, Fetal HB will do the job too. So this is the relation between Fetal HB and hydroxyurea.
 
 
Usually The reaction to this medicine differs from a person to the other, some react positively from the first month of trying it and others takes a while that is why it is approved to give it a try up to 9 months in order to judge whether it will help the patient or not. Some patients don't react to it at all. The usage of hydroxy is safe in thalassemia patients because it is used in very small amounts compared to cancer patients and by the way, many trails are going on these days to produce another drug which will do the same thing but not a chemotherapy.
 
Theoretically, in order to know whether hydroxurea will benefit you or not, a test called Xmn polymorphism is made. If the result is positive,it means you will benefit and if it is negative this means you won't, but practically doctors found that some times patients with the negative result react very good to hydroxurea and their hb rises to the extent that they eliminate transfusion and there explanation to this is that sometimes there are other unknown factors that help the body to react positively and this resulted in that many doctors try hydroxurea any way  because each patient is completely a different case.
 
Hydroxy too helps to suppress the bone marrow and therefore eliminate pressure on the bones resulting in no deformity and pains.

The most important thing to do when you start it, is monitor the kidney and liver fuction in addition the WBCs count in order to make sure that you won't have any side effects. One  of the good things about hydroxy is that if it happenes that you get any side effect by chance, it will vainish as soon as you stop it.

Also find below an important study about the role of hydroxy in eliminating transfusions in thal major patients done on 49 patients. Please show it to the doctors, hope they get convienced.
 
http://www.ams.ac.ir/AIM/09123/0013.pdf

Please feel free to ask anything
manal

Great post, Manal. I agree that for hydroxyurea to give maximum results, L-carnitine and magnesium should both be taken along with the drug. Research backs this up.

Thank you Andy

manal

Hi Manal,
This is a link to the research I found on use of L-carnitine and Magnesium with hydroxy urea. I will show it to my doctor at the next appointment.
http://www.ncbi.nlm.nih.gov/pubmed/19799627
I have got the hydroxy urea now and will start it tomorrow,inshallah L-carnitine I still need to get . Is there any brand you would recommend?
Thanks once again for your great guidance.
Zahra

Hello Zahra

Personally i use a local brand for L-carnitine (Syrup), but i know that the GNC brand is also very good. But the GNC are capsules, so may be you can disolve them in a juice or water and give them to your son though i prefer you use syrup cause he is still young.

You can check in your pharmacy, may be you find something good. You may also check for the one i am using because i know that they export. The comany that produces the L-carnitine is called MEPACO.

I really wish you Zahra all the best and hope that it will really work for your son, but don't forget that it needs patience,keep updating

manal

Hi Zahra
GNC also has liquid L-carnitine. Its available in GNC in two forms. One with 500mg pantothenic acid for every 1000mg of L-carnitine (white coloured bottle) and the other 15mg pantothenic acid for every 1000mg of L-carnitine (black coloured bottle). I use the black coloured bottle. You will be able to get it in Abu dhabi as my sister got it for me this time from the same place. (150 DHS).

maha

I'm really keen on hydroxy urea, but the last I checked with Adel's hemotologist in Spore (NUH) she said it doesn't work on Beta-Thal Major. She said they found that it works well with Thal Intermediaries only. I'm going to speak to her again next month on it. Can hydroxy urea taken with XJade?
Adel started XJade 3 weeks ago, at a low dose of 125mg, he is 10.5kg (3 years old), he's tolerating ok. His liver/spleen is noticeably smaller. We are very pleased with his recent progress after given him Vit E, D, Calcium & Magnesium (started about 2 months ago). He's much stronger and his bone density has improved since.  These days he is even walking confidently around without oxygen. Something we haven't done for the last 2 years!
As we have a chelation plan now, we are keeping closer watch on his HB/Liver/kidneys/Ferritin. Today HB is 9 and we transfused him (currently half way through transfusion). Last transfusion was 3 weeks. Before XJade, we were a little reluctant to transfuse him at 3 weeks. Normally wait till 3+ or 4 weeks.
After 1 year old, his spleen & liver were getting progressively bigger, we had to go for embolisation of splenic artery to reduce his spleen when he was 2 years old. He was so sick then he need transfusion every week, even 3 days then. The trend of spleen becoming big and frequent transfusion came back early this year, and we went for a 2nd splenic embolisation.
Adel's case is really tricky since he has congential heart disease + chronic lungs. I guess I had overlooked his nutritional aspects, chelation (I was under the impression that chelation starts when ferritin is over 2000 or something). We were just not informed. The doctors do not say very much and I can't rely on them to be pro-active. I'm really glad I had found a forum where I can express my thoughts and get 1st hand information. Thanks Thapal!