Dear Mariam,
Sorry because you could not understand… I never use to read back, when I write..
‘Red pilot’ !!!, he phoned me today.. his name is Khalifa, he is father of a child we transplanted, is a good friend of me and is always trying to help people in the thalassemia families. So, I understand, now.
1st question:
About Ferritin 1000 or 18 tx? I will follow both, which is first. Ferritin is not always reflecting iron but also a phlogistic process, as tonsils and noose.. Because iron enters with the transfusions given I think that the amount of blood given is the more precise marker to know how much iron he received already. Starting earlier you may give desferal only 2-3 times per week, but after 18 months approximately from first Tx if you give about 1 tx/month you should give regular desferal. This is because there is a calculation, for that I can extrapolate the expected liver iron concentration to be about 6 mg/ g of liver. In case of lower levels of iron concentration, desferal may be more toxic.
2nd question:
About hemopoietic stem cell transplant:
Stem cell transplant is made to correct the genetic defect that produces anemia in the thalassemia patients. We documented that the possibility of success of the transplant is different depending on the HLA compatibility and on the clinical conditions pre-transplant. This is what we call the class of risk. It is statistically identified, and derives from history of iron chelation (regular or irregular); hepatomegaly and presence or not of fibrosis in the hepatic portal spaces (this is seen in the pre-transplant liver biopsy).
it is always STEM CELL, we can take them from marrow, from peripheral blood or from other sources, as cord blood or as fetal liver and so on…. We chose the source based on the clinical need: when it is a standard transplant, from an HLA matched sibling the marrow is the best source, because it gives enough cells, and low GVHD, that is the graft versus host disease, an immunological reaction of the new marrow to the recipient. When we use a donor that is not matched, as the mother, we need more amount of stem cell to bypass the resistance and we need to manipulate them to eliminate lymphocytes, so we need much more cells. Then we take both, peripheral blood stem cells and marrow stem cells, so we can obtain more cells and of good quality to reach success. If there is an HLA identical donor this is the preferred donor. So, I suggest to look for an unrelated donor, in the bank. If no donor is available, then you will have the mother as alternative,(unless you deliver new child, potentially identical donor!!)
When I say HLA mismatched, I mean partially matched: always a child get half genetic heredity from mother and half from father. Only rarely it happens that by chance mother or father come out HLA identical (when mother and father share some thing between them two).
So normally the mother is identical to her chid fro those antigens that she transmitted directly and is different from the half transmitted from the father to the child. The mother has an advantage as donor, because during pregnancy there is a tolerance of the mother for those antigens, paternal, that she did not transmit to her child, and in the other side, the child became tolerant to the non inherited maternal antigens. Those are the background of using mother. She is better, but also a sibling that is mismatched for the non inherited maternal antigens may be used. Generally it is a child so not enough cells can be obtained from him. This is way we prefer the mother.
We transplanted 17 patients (of them 12 aged between 2 and 8 yo) from HLA haploidentical mother (haplo means 1 haplotype is identical and one haplotype is not). Of those transplanted, 15 are alive and 2 died (they were cured from thalassemia when they died). ) 11 patients had engrafted marrow, but only 9 are alive and without thalassemia, and 7 patients are alive and back to thalassemia. This is what I mean when I say about probability of 65% to be cured, 35-40% rejection, 12% of death.
I think that your child is in class 1 (regular chelation, no hepatomegaly, no fibrosis expected) at the onset of the transfusional history. He has hepatomegaly now, but this is going to improve with adequate transfusion regimen, suppressing his expanded erythropoiesis. Therefore, he does not have organ damage due to iron accumulation and to inadequate transfusions, and also he has low risk to develop comlications due to the good standard of therapy in your country. This is what I mean when I say in good clinical conditions. He is in class 1 but has no donor. Then, I think that you have time. So, you can wait for further improves in the transplant success. In any case, even a child in class 1 with an HLA identical sibling may die for transplant related complications (about 5%, that is 5 out of 100 children in class 1 may die as consequence of transplant). In case of not HLA identical donor, as I told you, about 10-12%, 12 out of 100, may die as consequence of transplant. This is low compared to other diseases, but still is a risk, so I can not tell you that risk is 0.
I fully understand your concern, probably you should look in the bank of MUD donors or wait (until he is 4-5 years old at least, may be), proceeding with adequate treatment. In any case if you are willing, you may apply for stem cell transplant officially in our institution (IME) and you will receive a program and presumed cost. The timing of every thing is complex, requiring before the transplant itself, a period of about 3 months for clinical investigation on donor and recipient, for harvesting and preparing the stem cells from the donor and giving some oral chemotherapy to the child. Only after this you may proceed to the transplant that may require at least 4 month after and sometime longer. So totally, is about 7-9 months at least.
To arrive in Rome, you may be supported by your ministry of health (so, ask for support, I do not know how) or by yourself that is costing about 120 thousands Euro, also the staying in Rome may require either or to rent an apartment, or to ask for help by an association of volunteers that help families during the stay in Rome, in a community manner.
Do not be hurry, take your time. New improvements are expected continuously..
Ciao,
Dr. Paola Polchi
IME Rome, Italy
p.polchi@fondazioneime.org
mobile phone: 0039 3384467829