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Can leuko-reduce prevent GVHD

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We use irradiation when GVHD is a concern, as is recommended by the Tech Manual. We would never rely on leukoreduction to prevent GVHD, especially when you can have up to (but not including) 5 x 10e6 leukocytes in a unit of blood. That is way too many to be relied upon to prevent GVHD.

BC

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As I understand it, even one viable lymphocyte could grow into a clone that could cause GVHD. So even after leuko-reduction, residual lymphocytes must be irradiated to make them incapable of dividing into more cells.

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Thanks to all the reply.

I asked this question just because one of my friends said that irradiation can't make all the lymphocytes lost its ability of dividing, he think leuko-reduce is safer.

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Leukoreduced is assuredly not safer especially with immunocompromised patients. The bone marrow transplant patient is highly susceptible to any residual leukocytes and irradiation of all blood and platelet products is the most effective solution to prevent GVHD.

Barr Antilla, MT(ASCP)

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I vaguely remember a study in the early 80's showing 25Gy, 30Gy and 35Gy, with the recommendation that 30Gy might be a tad better than 25Gy at getting complete inactivation in all products. But my memory fades me today -- actually, it faded years ago, but I forgot when ...

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I wonder if leuko-reduction before irradiation might make irradiation more effective since there are fewer wbcs present to zap. Hmm. Might be irrelevant, but just curious.

Didn't they try leukoreduction in Japan and had to go to irradiation of all units because they have such a genetically homogenous society some patients that were not immunosuppressed were getting GVHD from unrelated donors?

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We have had a situation at our little hospital. A doctor failed to order irradiated blood on a patient who recently had a kidney transplant (at a different facility). She has had transfusions in the past, non irradiated. The admit diagnosis had nothing to do with transplant, we were unaware that the patient had even had the transplant. We didn't question the order for LR packed cells. The patient received the units, no problem. The physician has now realized his error and is wondering if there are any monitoring tests that he can do for GVHD. Any help would be appreciated.

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The technical manual does not say anything about component irradiation for solid organ transplants. I would start investingating there. Maybe you did not even need irradiation for a kidney transplant. The AABB Transfusion reactions book has a good section on GVHD.

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In the AABB Technical Manual, the grading of GVHD is broken into four tiers and monitors are the severity of skin rash, total bilirubin levels, and persistent diarrhea.

Stage 1 T.Bili 2-3 mg/dL

Stage 2 T.Bili 3-6 mg/dL

Stage 3 T.Bili 6-15 mg/dL

Stage 4 T.Bili >15 mg/dL

This is from the 13th edition AABB pg.534

Although in reading the guidelines it seems that irradiation is necessary for ECMO transfusions, Bone marrow transplant transfusions(stem cell transplant patient), intrauterine transfusions, and familial (directed donor) transfusions. I would consult with your pathologist and determine what your policy needs to be, we do not take any extra precautions for irradiating blood for kidney recipients. The primary patients receiving irradiated products at our facility are post-marrow transplant.

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Different transplant programs have different rules about who gets irradiated blood products and who doesn't. Most of our patients post-kidney transplant don't get irradiated but one program insists upon it. Perhaps the physician should discuss the issue with the patient's coordinator/transplant surgeon.

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At our facility irradiated products are given at the specific direction of a physician's order. If a physician does not order irradiated products on a patient for which irradiation is most likely indicated, we contact the physician to suggest consideration of this option. Even if the physician is unsure irradiated products effectively reduce the chance for GVHD and associated complications. In addition, all of our Red Cells and Platelet products are ordered irradiated leukoreduced for most oncology, all potential transplant candidates, and all post transplant patients.

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what is the difference between leuko-reduction and irradiation ? and can we do irradiation instead of filtration ?

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Leukoreduction, by no means that I know of, can get rid off ALL WBCs in a blood product.  So if  you are worried about Graft-Versus-Host Disease in an immunocomprimised patient, you do not want to rely on leukoreduction alone.   The residual donor WBCs may "engraft" into the host recipient's system, and attack the recipient as a foreign threat.

So to avoid GVHD, you must kill all of the WBCs in the donor blood product.  This is accomplished with radiation.

Scott

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thanks  but my question: can we irradiate cellular product instead of leukoreduction you said " you must kill all of the WBCs in the donor blood product.  This is accomplished with radiation. " ?

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I guess irradiation  can inactivate the lymphocytes, but not deprave the antigens it takes, so it can not replace leukoreduction.

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11 hours ago, sherif said:

thanks  but my question: can we irradiate cellular product instead of leukoreduction you said " you must kill all of the WBCs in the donor blood product.  This is accomplished with radiation. " ?

Irradiation does not "kill" T lymphocytes per se, which are the cells that cause TA-GvHD, but what it does is disrupt the DNA within the nucleus, and this disruption prevents them from cloning.  As a result, they are unable to "reproduce" (for want of a better way of putting it) and so, instead of being able to form a clone within the recipient, will be removed from the circulation by natural apoptosis.  Prior to this apoptosis, once they have been irradiated, the T lymphocytes are relatively benign.

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To quote from a journal article: "Removal of leucocytes from various blood products has been shown to minimize Febrile nonhemolytic transfusion reactions, HLA alloimmunization, platelet refractoriness in multitransfused patients and prevention of transmission of leukotropic viruses such as EBV and CMV." Irradiation does not remove or inactivate the antigens that cause these problems.

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While I would not use leukoreduction as the primary method of preventing transfusion associated graft versus host disease in high risk patients, there is evidence that it reduces the incidence of this complication in patients not conventionally thought to be immunosuppressed.  These data are from the UK haemovigilance reports.  Lymphocytes are not killed by irradiation, but they cannot successfully proliferate, which is necessary for graft versus host disease to occur.  These  UK data make one wonder what the heck the USA experts (AABB and FDA) are thinking in not mandating universal leukoreduction 20 years after it was implemented in France, UK, Canada, etc.  So little cost, so many benefits. Three FDA committees have voted overwhelmingly that universal leukoreduction is clinically sound policy.  No action.  Many pleas to the AABB. No action.  This is one of the most cost-effective and important innovations in transfusion safety in the last half century.  It reduces suffering, morbidity and mortality.  It's cheap and easy.

 

The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion-associated graft-versus-host disease.

Williamson LM, Stainsby D, Jones H, Love E, Chapman CE, Navarrete C, Lucas G, Beatty C, Casbard A, Cohen H.

Transfusion. 2007 Aug;47(8):1455-67.

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3 hours ago, Neil Blumberg said:

While I would not use leukoreduction as the primary method of preventing transfusion associated graft versus host disease in high risk patients, there is evidence that it reduces the incidence of this complication in patients not conventionally thought to be immunosuppressed.  These data are from the UK haemovigilance reports.  Lymphocytes are not killed by irradiation, but they cannot successfully proliferate, which is necessary for graft versus host disease to occur.  These  UK data make one wonder what the heck the USA experts (AABB and FDA) are thinking in not mandating universal leukoreduction 20 years after it was implemented in France, UK, Canada, etc.  So little cost, so many benefits. Three FDA committees have voted overwhelmingly that universal leukoreduction is clinically sound policy.  No action.  Many pleas to the AABB. No action.  This is one of the most cost-effective and important innovations in transfusion safety in the last half century.  It reduces suffering, morbidity and mortality.  It's cheap and easy.

 

The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion-associated graft-versus-host disease.

Williamson LM, Stainsby D, Jones H, Love E, Chapman CE, Navarrete C, Lucas G, Beatty C, Casbard A, Cohen H.

Transfusion. 2007 Aug;47(8):1455-67.

This also makes you wonder - still - if all of these studies on Patient Blood Management today were really done on patients with 100% leukoreduced blood products - especially the studies done in the US.  It is not always listed in the controlled study parameters.  Also - if my memory has not faded completely(!) - I seem to remember leukocyte reduction being touted to decrease the same problems they are now after us to just "not give blood" for - the reasons so well detailed above. 

We have been on 100% leukocyte reduced RBCs here (from our blood supplier - Blood Systems, Inc) for a couple of decades now - and we see VERY few transfusion reactions.  While that is not the only reason not to give blood - why are the posited post transfusion complications still the same?  Did leukoreduction not work?  Or are we still fighting the same complications because some of the US still has not adopted universal leukocyte reduction?  Leukocyte reduction seems to have helped our patients a lot.

Just curious -

 

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On 2/19/2018 at 10:36 AM, Malcolm Needs said:

Irradiation does not "kill" T lymphocytes per se, which are the cells that cause TA-GvHD, but what it does is disrupt the DNA within the nucleus, and this disruption prevents them from cloning.  As a result, they are unable to "reproduce" (for want of a better way of putting it) and so, instead of being able to form a clone within the recipient, will be removed from the circulation by natural apoptosis.  Prior to this apoptosis, once they have been irradiated, the T lymphocytes are relatively benign.

thanks alot

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