Can hydroxyurea help in a case of excessive fetal haemoglobin

Hi, I just came across this site on google. I have a 3 yr old daughter. She was diagnosed a thal intermediate when she was 1 yr. The pedaic. Thought that her spleen n liver were enlarged on clinical check up and told us to get n HPLC done
Her results were
Hb F 92.1
Hb A 5.1
Hb A2  2.7

Her hb at this age was 9.5

However since then we have got d
DNA testing done . My husband is a thal trait IVS 1-5
I am negative for the 5 common Indian mutaions
My daughter has the same gene as my husband but negative for cap site +1 (A->C) as well as other mutations in promoter region and exon 1&2 of beta glob in gene
Negative for deletion /duplication for alpha thal
Negative for HPFH
she is doing just fine
Has good appetite
Does not have very low immunity
Is very thin and slightly below avg in height ( I too am short)

However her hb now is 8.7 but her spleen has significantly enlarged to  about 10cms. Her liver too is slightly enlarged

The doctors that we have seen say that they have never come across a case like this. They all want us to repeat her HPLC ( which we have done 4 times with similar results

They want us to repeat the DNA tests. We don't know of any other reliable place in India

Intact one of the doctors recommended we try hydroxyurea even though she has been tested for XMN I polymorphism (-158>T) in the G Gamma gene of beta thal chromosome and it shows
(-/+) polymorphism in heterozygous form
which the same doctor explained means that the drug might not work in the Childs case
so the other doctors tell us not to bother with the drug and just wait n watch
We need help in figuring
1) whom to consult in India. Or outside
2) how to get reliable DNA testing done
3) should we try the drug....... What are the side effects

Pls help
Pooja

Pooja,

Welcome to thalpal. Thal (Intermedia) is a complex condition and needs to be monitored carefully. You can read the Thal (Intermedia) section in the Standard of Care Guidelines given by Children's Hospital Oakland. You can find the pdf at http://www.thalassemiapatientsandfriends.com/index.php/topic,1762.0.html

Also, you can get in touch with Pooja Gill whose son Prat has been treated by Dr. Marwaha. You can find the post for Prat's treatment at http://www.thalassemiapatientsandfriends.com/index.php/topic,2602.0.html

For side effects of Hydroxy, you can follow links to http://www.ncbi.nlm.nih.gov/pubmed/21602718

Efficacy of hydroxyurea in providing transfusion independence in β-thalassemia.
Ansari SH, Shamsi TS, Ashraf M, Perveen K, Farzana T, Bohray M, Erum S, Mehboob T.

Source : Department of Pediatric Hematology, National Institute of Blood Diseases, Karachi, Pakistan. ansarisaqib@hotmail.com
Abstract

BACKGROUND:
Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for β-thalassemia major. This prospective interventional trial serves as a follow up to our similar earlier study that evaluated the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with β-thalassemia major.

METHODS:
One hundred fifty-two patients with β-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.

RESULTS:
One hundred forty-six of 152 patients were evaluated after 24 months of follow up; 6 patients were either lost to follow-up or withdrew consent. Grade 1 myelosuppression was observed in 4 patients and diarrhea in 2 patients. Sixty children (41%) did not require any transfusion after using HU; 57 patients (39%) showed partial response with greater than 50% reduction in PRC transfusion; and 29 patients (20%) were nonresponders with less than 50% reduction in PRC transfusion. The mean volume of PRC transfused was reduced for all patients.

CONCLUSIONS:
HU was found to be safe in patients with β-thalassemia major, and resulted in the reduction of transfusion requirement and in an increase in the interval between transfusions.

You can read more details on use of hydroxyurea by surendra's daughter at http://www.thalassemiapatientsandfriends.com/index.php/topic,4464.0.html

I would say that because there is already a great ability to produce HbF, that hydroxyurea should be tried, as it works by raising HbF and is most effective in patients who already have a proven ability to produce fetal hemoglobin.

Thank you for your response. My question is that hbA1 A2 n F are % of total Hb. If there is an increase in HbF (which is already about 95%) how will it help in rise of total Hb. I don't really know if this is an intelligent question but I am really confused becoz different doctors are of different opion in my case. Some say we must give it a try. Other say that success rate in such small children is not very high. Pls help.

Pooja,

The HbF level is used to tell if hydroxyurea is working. If the drug works, HbF levels should increase as a percentage of the total Hb, and in this case there is hope that the drug will stimulate a higher production of HbF, so that the total Hb also rises. One of the goals of thalassemia management is to decrease the amount of ineffective erythropoiesis in the bone marrow. This is achieved by transfusion in major patients, as the higher the Hb, the less ineffective erythropoiesis that will occur. This ineffective erythropoiesis is what causes the bone marrow to be overactive and cause changes to the bones, weakening them and causing deformities in the bones and skull. So, it is also an important part of managing thal in intermedias. So even if the total Hb percent does not increase, hydroxyurea may be effective in lowering ineffective erythropoiesis, and reducing things like changes to the bone and also spleen size, as the spleen filters out the bad red cells produced in the bone marrow. If the HbF does not show significant change after 6 months and the HbF has not risen, there is less chance of success with the drug. The Hb of the child is still higher than where transfusions would be indicated but the possibility of a continued drop in Hb as she gets older, is a good reason to find out if hydroxyurea can work for her. If it helps to maintain an Hb around 9, she will be able to avoid transfusion. If her Hb continues to drop and her growth and development are affected, transfusions would become necessary.

And one note. Better drugs than hydroxyurea are in development. This will create more options when she is older. The new generation of Hb inducing drugs should have a much greater affect on Hb than hydroxyurea does.

And one note. Better drugs than hydroxyurea are in development. This will create more options when she is older. The new generation of Hb inducing drugs should have a much greater affect on Hb than hydroxyurea does.

Dear Andy,
Whether the above said better drugs will be helpful in Th. Major?

Hydroxyurea is not widely used with thal majors, but is suggested as a therapy in countries where treatment is not good. I don't think it has enough value for majors to be used routinely. Hopefully this will, change with the newer hemoglobin inducing drugs.

Thank you Andy for the information and support. I want to also ask you that though I have been reading about side effects of hydroxy urea I still don't understand them. I mean what is the reason the some doctors are against its use. Are there any major dangers? Also in case the drug works then is it to be taken lifelong. In case it doesn't work would the patient be worse off than when they started it? 

The side effects of low dose hydroxyurea as used in thalassemics are minor at the most. It has not been a concern. Often doctors are not aware of this because they are familiar with the drug being used in much higher doses in conjunction with chemotherapy in cancer patients, and are not aware that it can be used in thalassemia, and avoid it because of the chemo connotation. Some doctors who are familiar with the drug feel that the effects are not strong enough to bother using the drug, so it is used mainly with intermedia patients who can benefit more from the slight rise in Hb level. However, studies in countries like Algeria and Iran have shown much more promising results with long term usage of hydroxyurea, so there is some debate on just how much value the drug has.

It would require continued use of the drug for a continued effect, but I would not say lifetime use because the drug will be surpassed by new fetal hemoglobin inducing drugs in the coming years. Regardless of which drug used, it will be an ongoing therapy. There is no long term change made by using the drug, so there is no concern about taking the drug and then ceasing it if it does not work well enough to be of value.

Thank you Andy. I wrote to Pooja Gill as you suggested but haven't got a response from her yet. Is there any other way I can get in touch with. Also is there any place in India where I can get wheatgrass spray. Thank you, Pooja

Haven't heard about Wheat grass spray? Are you talking about Syrup?
Though Wheatgrass tablets are availabel in Pune and Mumbai.

No I wanted to know about the spray. But do tell me which tablets and syrup a good. Especially for a baby.

Sorry, i am only aware about the Tablets of wheat grass and within short span i m going to restart it.

Hi Andy, after reading your reply and reading loads about thal, hydroxy, spleen etc etc we decided to give hydrea a try. So the doctor told us get a few baseline tests done before we start like Complete blood count, liver n kidney function etc. To our surprise my daughter's hb had risen from 8.2 to 8.6. Also her rectic count had fallen to 2.6 from a high of 8. So the doc told us to wait a month and get the tests done again. What I want to know is what does this change mean. Do the counts just fluctuate or does this mean a change for improvement. Also rectic count is an indication of bone marrow activity. Since it is almost normal should we still go for hydroxyurea to supress bone marrow activity.

Please tell me wahtever you think. Even if u think these changes are insignificant.

Also do u have any suggestions about doctors in Delhi, india. Coz I am fed up of the different views and opions that they have on what should be done.

Thank you
Pooja

Hi Pooja,

That's good news to see the Hb is stabilized. Because the Hb has maintained above 8 so far, I see no rush to start hydroxyurea. The drop in retic count is encouraging, but I wouldn't place too much importance on the level until the low level has been repeated. Are you giving her any supplements that would account for an increase in Hb, such as wheatgrass or other supplements like folic acid?

I don't know anything about the doctors in Delhi. Perhaps some other members can help with this. If not, we can look on our Facebook group for an answer.

For now, I would hesitate on introducing hydroxyurea, unless the Hb goes below 8.