Mother to Child or Haploidentical BMT

Dear all

When you want to do a bone marrow, your first option is a matched sibling and if not, then the second option is unrelated doner or unrelated cord blood. The third option which i read about was haploidentical transplantation where the doner in this case is the mother of the patient EVEN if she does not match.  The idea of this is that they depend that half the DNA of the patient comes from the mother and therefore they work on this. The mother is involved and not the father( though he has an equal chance as he carries the other half of the DNA ) because during birth the mother and the baby exchange some blood during deliveryand........something happens that makes transplantation more suitable from the mother. I really can't understand this part as it is very scientific.
But the probability of sucess is 68% fromthe mother.

I found this information on site of the Egyptian Thal Association(ETA) and there address is www.Thalass-eg.com
This lecture was said in the conference that was held in Cairo this year. You can download this lecture which you will find it in the second seccion , 3rd lecture on the 8th of May.( Sorry i don't know how i can make the link)

So anybody has any information about this haploidentical???


Manal

 Dear Manal that's true Prof.leucarally do this prosedure right now deuring my stay in italy i saw many cases 1: BMT from match donor 2: BMT from the mother even she is not matching 3: BMT from unrelated donor ..    from the mother i met one case not successful and there is rejiction  also from the same donor there is a risk to have rejiction .. and a bout from the unrelated donor i understand from some Drs they are plan to do it for some cases and now i have one of my close friend who made for his son BMT from his wife i have a contact with him almost every week and every thing is smooth and ok but there is some kind of skin GVHD ... 
 
                             khalifa
                    state of kuwait

Dear all

As i posted before, i have sent my daughter's blood sample to Italy to check if she matches with my son or not for BMT and till now i didn't receive the result.
Today when i asked my doctor about the 2nd best option if the result was negative, she gave me two choices.
The options are: unrelated doner
                        unrelated cord blood
                        haploidentical transplantaion
                        having a new baby

She told me, the 2nd option is the baby ( provided that it is through VITRO and this is affordable in a way although it is expensive since they take away the mutated thal gene from the embryo.  She added that they can also adjust this embryo to match the HLA type of my son, but unfortunatly this cost ''millions'' as she said and can not be guranteed. By the way she gave me the names of the doctors who do this and they are in Cyprus.

She added, that the third option would be the haploidentical transplantation.

That was all

Take care

Manal

Haploidentical transplantation is a fairly new process that is still somewhat in the experiemental stage and the results do not yet have the same success rate as the traditional bone marrow transplant procedure. It is not known why it works, as only half of the genetic material is a match, but there is speculation that whatever mechanism is at work during pregnancy that prevents rejection of the fetus by the mother's body (since the half of the genetic material from the father of a fetus is foreign to the mom's body, why isn't the fetus rejected?) also protects the recipient's body from rejecting the bone marrow of the mother.

It is a very interesting development in BMT research, as it greatly increases the amount of potential donors. Dr Peter Sodani spoke about this subject at the Dubai TIF conference, in January, 2006 and said they had tried haploidentical transplantation on 15 patients and it had succeeded in 9 of them. This is a lower success rate than with typical BMT but improvements in the success rate are expected as they try it with more patients.

Manal, I would suggest contacting the Italian clinic and asking what the current success rate is and also if they will do a BMT on an intermedia or if the risks outweigh the potential benefits.

At the TIF Conference in Dubai in 2006, I attended the talk about mother to child BMT given by Dr Sodani. At that time, it was a fairly new process and if I remember correctly, this has been performed on 16 patients and success had been found in 9 of the cases, which was not a great success percentage, but did give hope that this process could be refined and better results could be achieved.

I have two questions.
1) Has this method been continued by Dr Sodani, and if so, what is the current success rate?
2) In 2006, Dr Sodani explained that there was no clear explanation why a mother to child BMT would work, but he speculated on a possible reason. Has the science advanced? Does Dr Sodani have a better understanding of why this process works for patients than he did in 2006?

I've talked to Dr. Sodani, and these are his answers:

1) "Has this method been continued by Dr Sodani, and if so, what is the current success rate?"

Thalassemia free is 70%,rejection 23% and mortality 7%. The best results are with very young patients.

The most recent scientific paper has been published on June 2011:
Pediatric Reports:T cell-depleted hla-haploidentical stem cell transplantation in thalassemia young patients
http://www.ncbi.nlm.nih.gov/pubmed/22053275

The first preliminary results were published on Blood Journal on November 2009:
Blood Journal:Purified T-depleted,CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia
http://bloodjournal.hematologylibrary.org/content/115/6/1296.abstract

2) "In 2006, Dr Sodani explained that there was no clear explanation why a mother to child BMT would work, but he speculated on a possible reason. Has the science advanced? Does Dr Sodani have a better understanding of why this process works for patients than he did in 2006?"

The scientifc explanation is in the Blood Paper that I have mentioned above. Anyway, you can read it in this paper written by T. Ichinohe, one of the most famous experts of feto-maternal microchimerism:
Long-term feto-maternal microchimerism revisited: Microchimerism and tolerance in hematopoietic stem cell transplantation.
http://www.ncbi.nlm.nih.gov/pubmed/21327150#

For your convenience, I paste it here:
Bidirectional fetal-maternal cell traffic during pregnancy gives rise to stable persistence of minute amounts of allogeneic cells both in the mother and in her offspring, a phenomenon called long-term fetal or maternal microchimerism. Over the past decade, increasing attention has been devoted to elucidating the biological relevance of such reciprocal microchimerism, unveiling its conflicting roles in either immune sensitization or tolerance induction against fetal or maternal alloantigens. Recent studies in mice and humans have highlighted the significance of fetal-maternal microchimerism in the induction and maintenance of CD4(+)CD25(+) and CD8(+) T regulatory cells that counterbalance the immune responses to fetal or maternal antigens mediated by T effector cells. Consistent with these observations, T-cell-replete hematopoietic stem cell transplantation between mutually microchimeric mothers and their HLA-haploidentical offspring has been shown to be feasible, although the degree of microchimerism-associated tolerance appears to substantially differ among the cases.
Since in vitro or trans-vivo assays to detect antigen-specific tolerance in the context of the T regulator versus T effector balance are now available, future clinical studies incorporating these tests into the criteria for donor selection are warranted to more precisely define the relevance of fetal-maternal microchimerism in allotolerance and immune homeostasis after hematopoietic stem cell transplantation

He has also published a paper on Blood about this topic
Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+ CD25+ T-cell-dependent mechanism.
http://www.ncbi.nlm.nih.gov/pubmed/16150938

JJ van Rood, a great expert in BMT applied to different diseases has also published a paper on this topic:
The effect of noninherited maternal antigens in allogeneic transplantation.
http://www.ncbi.nlm.nih.gov/pubmed/15846576

Please notice that Prof. Lucarelli started doing haploidentical mismatch transplants using the mother for patients in advanced leukemia. These are the 2 scientific papers published on Bone Marrow Transplantations:

1991
Mother as HLA haploidentical marrow donor for children with advanced leukemia.
http://www.ncbi.nlm.nih.gov/pubmed/1878671

1995
Haploidentical bone marrow transplantation from mother to child with advanced leukemia
http://www.ncbi.nlm.nih.gov/pubmed/8528168

When in 2002 Prof. Lucarelli and Dr. Sodani started doing Haploidentical bone marrow transplantation from mother to child with thalassemia , they already had 10 years of experience using the mother as haploidentical donor.

Another important fact that we want to emphasize is that the Blood paper of Dr. Sodani has been officially positively commented on another Blood paper written by Ann Woolfrey, who works in the most famous BMT center in the world, the Fred Hutchinson Cancer  Research Center in Seattle:
Blood: Breaking barriers
http://bloodjournal.hematologylibrary.org/content/115/6/1112.full

An excerpt of the abstract:
Finally, selection of a maternal donor exploited the potential for feto-maternal microchimerism to induce immunologic tolerance. Taken altogether, these strategies allowed utilization of a relatively conventional regimen that did not contain total body irradiation. Although not perfect, the results are extremely promising—a reasonably small risk for mortality with a reasonably high rate of engraftment. Among patients who did not achieve full donor chimerism, disease symptoms were ameliorated in those with mixed donor-host chimerism and autologous hematopoiesis resumed in those who rejected their graft.
The fact that these results were obtained in a group of mostly class 2 to 3 thalassemia patients is even more remarkable.