Right.  So leukoreduction helps prevent those pesky febrile transfusion reactions, and irradiation helps prevent GVHD.  They are not the same thing, after all!

Scott

I know we have users from multiple countries here, another confounding point is that the US considers leukoreduction to have less than 5*10^6 WBCs left, but the EU standard is less than 1*10^ WBCs in the product.

One nice thing about having implemented pathogen reduction for platelets is we can stop irradiating for GVHD, since the pathogen reduction also stops WBCs from being able to reproduce (the platelet products are still coming off the machine leukoreduced too).

32 minutes ago, Eman said:

I know we have users from multiple countries here, another confounding point is that the US considers leukoreduction to have less than 5*10^6 WBCs left, but the EU standard is less than 1*10^ WBCs in the product.

One nice thing about having implemented pathogen reduction for platelets is we can stop irradiating for GVHD, since the pathogen reduction also stops WBCs from being able to reproduce (the platelet products are still coming off the machine leukoreduced too).

I am a little worried about this.  The irradiation is controlled by various things, such as those strips that show whether or not a blood component has actually been irradiated or not, whereas the leukocyte reduction filters are not tested each time, but usually only now and again.  This means that the testing for leukoreduction allows for some units to "slip through the net" if they have not actually been sufficiently leukoreduced because the filter has not worked as expected, or whatever.

You may just have been lucky so far.

"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."

The short (sort of) answer is that while leukoreduction reduces acute transfusion reactions, likely including TRALI and TACO, reduces alloimmunization to white cell and red cell alloantigens, reduces the risk of GVHD, reduces the risk of organ failure due to inflammation, etc. it does not completely abrogate these risks. Platelet transfusions still cause inflammatory type reactions in about 1% of transfusions due to soluble mediators in the plasma such as IL-6 and CD40L.  There is still lots of stored plasma in red cells and, in particular, platelets, allogeneic antigen, both soluble and cell associated, mediators such as VEGF, CD40L, IL-6, etc. that are not removed by leukoreduction at the time of manufacture.

The red cells and platelets deteriorate and release mediators such as free hemoglobin, free heme, platelet granule contents, etc. that are both biologically and clinically active, causing some of these complications even after leukoreduction. There are some residual viable white cells, if not irradiated, so even minimal amounts of allogeneic white cells may have effects.  We don't know.

Then there is the routine, inventory driven, unfortunate use of ABO non-identical plasma and cells that creates immune complexes that almost certainly cause bleeding, endothelial damage and inflammation.  Iatrogenic immune complex disease, if you will,  that contributes to cellular damage and organ injury.  Thus there are still plenty of candidate mediators for harm. 

Nonetheless, I would suggest leukoreduction is the most important advance in transfusion practice since the invention of serologic testing (Coombs test) and infectious disease testing to prevent hemolytic reactions and viral disease transmission respectively.

 

It is our speculation, and we have randomized trial evidence in acute leukemia and pediatric cardiac surgery, that removal of stored supernatant immediately prior to transfusion by washing, along with leukoreduction and ABO identical can strikingly improve clinical outcomes by reducing immunomodulation and inflammation.  When ABO identical red cells or platelets are not available, we remove 95% of the supernatant from group O red cells or platelets for non-O patients.  References on request.

On 2/23/2018 at 8:15 AM, Neil Blumberg said:

"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."

The short (sort of) answer is that while leukoreduction reduces acute transfusion reactions, likely including TRALI and TACO, reduces alloimmunization to white cell and red cell alloantigens, reduces the risk of GVHD, reduces the risk of organ failure due to inflammation, etc. it does not completely abrogate these risks. Platelet transfusions still cause inflammatory type reactions in about 1% of transfusions due to soluble mediators in the plasma such as IL-6 and CD40L.  There is still lots of stored plasma in red cells and, in particular, platelets, allogeneic antigen, both soluble and cell associated, mediators such as VEGF, CD40L, IL-6, etc. that are not removed by leukoreduction at the time of manufacture.

The red cells and platelets deteriorate and release mediators such as free hemoglobin, free heme, platelet granule contents, etc. that are both biologically and clinically active, causing some of these complications even after leukoreduction. There are some residual viable white cells, if not irradiated, so even minimal amounts of allogeneic white cells may have effects.  We don't know.

Then there is the routine, inventory driven, unfortunate use of ABO non-identical plasma and cells that creates immune complexes that almost certainly cause bleeding, endothelial damage and inflammation.  Iatrogenic immune complex disease, if you will,  that contributes to cellular damage and organ injury.  Thus there are still plenty of candidate mediators for harm. 

Nonetheless, I would suggest leukoreduction is the most important advance in transfusion practice since the invention of serologic testing (Coombs test) and infectious disease testing to prevent hemolytic reactions and viral disease transmission respectively.

 

It is our speculation, and we have randomized trial evidence in acute leukemia and pediatric cardiac surgery, that removal of stored supernatant immediately prior to transfusion by washing, along with leukoreduction and ABO identical can strikingly improve clinical outcomes by reducing immunomodulation and inflammation.  When ABO identical red cells or platelets are not available, we remove 95% of the supernatant from group O red cells or platelets for non-O patients.  References on request.

Well Neil, it looks like a lot of folks may be dragging their old IBM 2991 cell washers out and dusting them off.  Great information, thanks.

On ‎2‎/‎22‎/‎2018 at 2:01 PM, Malcolm Needs said:

I am a little worried about this.  The irradiation is controlled by various things, such as those strips that show whether or not a blood component has actually been irradiated or not, whereas the leukocyte reduction filters are not tested each time, but usually only now and again.  This means that the testing for leukoreduction allows for some units to "slip through the net" if they have not actually been sufficiently leukoreduced because the filter has not worked as expected, or whatever.

You may just have been lucky so far.

Curious what you mean, the pathogen reduction (PRT) is FDA cleared and accepted to replace irradiation due to GVHD concerns.  Prior to implementing that our platelets were 100% irradiated, just to be safe.

There is a rWBC threshold for the PRT process, we still do QC on rWBC on the platelets to make sure we're lower than the limit. And RBCs get irradiated when patient needs indicate.

But totally agree that LR filters do not remove 100% of WBCs, and since it's not 100% tested some over the limit may slip through. More of concern with RBCs though, which are irradiated as needed. The apheresis tech is pretty reliable when it comes to LR.

11 hours ago, Eman said:

But totally agree that LR filters do not remove 100% of WBCs, and since it's not 100% tested some over the limit may slip through. More of concern with RBCs though, which are irradiated as needed. The apheresis tech is pretty reliable when it comes to LR.

This is precisely what I mean - that not 100% are tested and some may slip through.

Admittedly, there would have to be a "coming together" of unfortunate circumstances, but, if one of these units does slip through, and it is given to someone who is immunosuppressed, and they happen to share a partial HLA type, then there could be trouble.

If, on the other hand, the unit is irradiated, but for some reason the irradiator isn't working, or it is, but the strip doesn't change, then that is a "fail safe" system, as, I hope, the unit would not be transfused.

22 hours ago, Eman said:

the pathogen reduction (PRT) is FDA cleared and accepted to replace irradiation due to GVHD concerns.  Prior to implementing that our platelets were 100% irradiated, just to be safe.

Is this true for all of the pathogen reduction methods or only some of them?  The new Circular of Information keeps qualifying the statements to say " if approved for GVHD prevention".

19 hours ago, cswickard said:

Is this true for all of the pathogen reduction methods or only some of them?  The new Circular of Information keeps qualifying the statements to say " if approved for GVHD prevention".

Fair question, I'm sure it depends on if the manufacturer makes the claim or not. Cerus is the only licensed PRT provider/system in the US and their package insert states it will "potentially reduce the risk of TA-GVHD." Not as strong a statement as I expected, but our medical leadership has taken it to heart. Perhaps we will see a case report in a few years, hopefully not!