abo incompatibility and stem cell transplantation

[mrpessimist]

I'm very interested to trasfusion therapy in the setting of stem cell transplantation expecially when there is ABO incompatibility.

I woulld exchange my experience with somebody else

[Liz]

I am interested in reading your exerience, please do post.

[Yanxia]

I will give the red cells the type as the donor and plasma platelet the type same as recipient when the minor mismatch transplant;

when major mismatch I will give red cells the recipient type , plasma and platelet the donor type;

when major and minor mismatch I will give O red cells and AB plasma and platelet.

The platelet mentioned above is aphereis platelet not manual platelet.( I don't know if this name right or not)

[mrpessimist]

The transfusion protocol you have mentioned Shily is the correct one but in the setting of stem cell transplantation is not the only one action we have to made.

Prevention of hemolityc complication es. passenger lymphocyte syndrome begin at the moment of the selection of donor. I think that the better one is HLA matched related if possible or unrelated ABO compatible but is not so frequent. At Perugia in Hematology Department directed Prof.Martelli we have another challenge because the most used donor id aplodentical one. In this setting the probabilities to choice ABO identical one is more. T depletion we used with Clinimacs help us to prevent some hemolityc complication in ABO major and minor incompatible settings ( acute one) deprivating cellular infusion product of red cells and plasma. In major ABO mismatch we test the donor isoagglutin titles from pre-transplant period until there is engrafment of red cell of donor origin to monitor the onset of delayed red cell engrafment or Pure red cell aplasia.In this complication I am interested to know the therapy if plasma-adsorbition plasma-exchange soppression of GVHD profilaxis or rituximab or other more.

To be continued

Thanks

[Yanxia]

:)Sorrymrpessimist, I understand it so simplicity. I expected to see the discussion , continue!

[CM2]

A few questions for you:

Are you saying the majority of your transplants are haploid transplants (only 50% HLA matching)?

And that you create persistent chimeras intentionally where both blood types are co-produced for an extended period?

Does your lab perform T cell reduction for the primary purpose of red cell/plasma reducing a graft?

I think I must have misunderstood at least some of your points because all 3 of those things would be considered very unusual protocols here in the US =)

Standard practice for allo transplants for my institution is to find a preferably related donor who is as fully HLA matched as possible (6/6). For patients with poor outcome translocation leukemias they may rarely consider an unrelated donor 5/6 hoping for increased graft vs tumor activity - but with reluctance since it comes with the price of increased graft vs host. Im guessing you call graft vs host disease "passenger lymphocyte syndrome". The process where the T cells produced by the new graft become reactive to proteins on recipient healthy tissues rather than abnormal cancer clones or normal damaged/sick cells which Should be removed by the body. Here in the US, haploidentical transplants (in laymans terms, HLA matching of 3/6 or less - not matched at all) are only performed with an IND - a research protocol approval only, it is not standard practice.

We have only had experience with one T cell depletion we performed on the Baxter Isolex for a haplo transplant. It had good T cell reduction but the patient got terrible GVH anyway and it did not end well. I would guess thats because starting out with a T cell reduced graft is only part of the story, your new graft will eventually produce new T cells on its own which all come with the same chance of becoming reactive to your recipient. One bad sunburn where the T cells come running to check out all the damaged skin and all your work is undone. We would never consider using T cell depletion as a method of reducing rbc/plasma content in a graft since it is such involved manipulation. You will always lose TNC and whats more important - having enough TNC to ultimately engraft or managing short term hemolysis?

Our allo transplants are pretty much all fully ablated meaning the existing marrow is wiped out, so once the existing original rbcs die out over their normal life they do not come back. This means hemolysis is transient and generally manageable - its rare our related allos require more than 2-3 units rbcs for support in that lag between wbc engraftment (12 days )and full restoration of hematopoeitic potential. (2 months). Managing infused blood types in that time period we use the same algorithm that shily describes, basically choosing blood/products that will not react with either type.

If I would guess if you had a persistent chimera created, trying to plasma pherese out the ABO antibodies would be futile since they are generally high titer and quickly replaced. RBC exchange with O units might buy you some time. Certainly dialysis could become necessary if there was persistent hemolysis from new marrow produced rbcs. Graft vs host prophylaxis generally targets the T cell mediated tissue reactions which are sort of separate to me from rbc hemolysis issues. I dont know anything about how effective off label use of rituximab is for that type of autoimmune anemia. I know they use it in mismatched kidneys but the mechanism of how anti-cd20 could affect rbc hemolysis is a mystery to me. Something to look at for lunchtime I suppose =).

[mrpessimist]

AVERSA 2005 VFull Haplotype-Mismatched Hematopoietic Stem-Cell.PDF

AVERSA 2008 Haploidentical haematopoietic stem cell transplantation for acute.pdf

AVERSA 1999 TREATMENT OF HIGH-RISK ACUTE LEUKEMIA WITH T-CELLÐDEPLETED STEM.pdf

[mrpessimist]

for CM2 to better understand tha transplantation protocol of our institute that is well known at world level

[mrpessimist]

I never said that passenger limphocyte sindrome is a gvhd related complication

[rravkin@aol.com]

I never said that passenger limphocyte sindrome is a gvhd related complication

Can you explain what "Passenger Lymphocyte Syndrome" is??

[mrpessimist]

A well-recognized syndrome of immune hemolysis following BMT has become known as the passenger lymphocyte syndrome.It occurs in a minority of the patients for whom there is a minor ABO blood group mismatch between donor and recipient. Hemolysis usually has its onset between Days 5 and 15 after transplant, is often abrupt in onset, and may be severe, with a rapidly dropping hemoglobin

level, signs of intravascular hemolysis, and renal failure.

Anti-A and/or anti-B directed against antigens on the patient’s RBCs are found in the serum and in eluates from the patient’s RBCs. Hemolysis subsides as the patient’s residual incompatible RBCs are destroyed and are replaced by newly produced RBCs of donor origin andlor by transfused

group 0 RBCs.

Detailed serologic studies have indicated that the relevant serum antibody is not present in the immediate posttransplant period but is first detectable around the time hemolysis begins. Therefore, passive transfer during infusion of the donor’s plasma with the marrow cannot account

for the presence of the antibody. Moreover, antibody production and hemolysis generally occur before clinical evidence of engraftment, during the time that pancytopenia caused by the BMT preparative regimen is present and before immune reconstitution of the patient, which indicates that the antibody is not a product of a newly engrafted immune system. Instead, the syndrome has been attributed

to the production of antibody by rapidly proliferating passenger lymphocytes that are transfused with the donor marrow. There have been similar reports of the development of antibodies after minor mismatching within other blood group systems, such as Rh,Kidd, and Lewis,but these mismatches have caused in vivo hemolysis only rarely.

It is wise to monitor at-risk BMT patients between Days 5 and 15 after transplant by using serial measurements of hemoglobin, hematocrit, bilirubin, and lactate dehydrogenase and the performance of direct antiglobulin tests and tests for donor-derived antibody. In most instances, hemolysis may be managed by the transfusion of compatible RBCs, the empirical use of corticosteroids, the avoidance

of ABO-incompatible plasma components, and the maintenance of adequate renal perfusion.

Of particular concern are the occasional reports of massive hemolysis after minor ABO-incompatible marrow or peripheral blood stem cell allotransplantation n,whichleads to renal insufficiency and even to fatal multisystem organ failure.In these cases the amount of hemolysis could not be explained solely on the basis of destruction of the patient’s ABO-incompatible RBCs by anti-A or anti-B. This finding led to the remarkable conclusion that, in these patients, rather large volumes of transfused group 0 RBCs were hemolyzed in addition to the patients’ own RBCs, even though the only RBC antibodies present in the sera and eluates were anti-A or anti-B.

These cases of massive hemolysis in BMT patients with the passenger lymphocyte syndrome provided the impetus for suggesting the presence of “bystander immune hemolysis,” that is, immune destruction of cells that are negative for the antigen against which the relevant antibody is directed. Although the mechanism has not been determined, lysis of antigen-negative blood cells occurs in other settings, such as posttransfusion purpura, wherein alloantibody against antigens on a donor’s platelets, usually anti-PlA1 (anti-HPA-1a), can destroy autologous platelets that are genetically nonreactive with the antibody.In addition,complement and IgG sensitization of antigen-negative autologous RBCs has been described in hemolytic transfusion reactions (HTRs),which indicates that antigen-negative RBCs are affected by the immune destruction of antigenpositive RBCs. Although difficult to document, bystander immune hemolysis has also been suspected as a mechanism

contributing to the severe HTRs in patients with sickle cell disease and in other clinical settings.