Anti-CD38 therapy discontinued

[David Saikin]

A patient who has been treated w anti-CD38 is no longer having that treatment.  Antibody screen is now negative.  Is it prudent to continue K typing?

Thanks in advance.

[Joanne P. Scannell]

We do, 'just because' ... it's easy to find K-Neg RBCs and one never knows if they are going to try it again so we don't want to deal with switching around.  We have one patient who seems to be chronically infused with this stuff!

[David Saikin]

That's what I've been doing also.  Thanks for the response.

[jayinsat]

We do not unless the patient has Anti-K. Darzalex is just a transient interfering substance. If there is no DTT neutralization required and no antibody detected, it is not necessary. Plus, I don't see how I can charge for the antigen typing in that scenario. I think that risks fraudulent billing.

 

[Ensis01]

It makes sense to have a K neg policy while the patient is on anti-CD38 therapy, i.e. K neg units are given because DTT meant Kell antibodies could not be ruled out. Once anti-CD38 therapy is finished and if the patient never had anti-K and you can rule it out I see no reason to keep giving K neg units.

[JoyG]

I agree with discontinuing the K negative units.  We have the same policy as Ensis01

[AuntiS]

Same.  We don't select K negative units once off the dara.

Here in Canada, all our units are K typed by Canadian Blood Services.  It wouldn't necessarily be more work to select K neg units, but we feel it isn't needed.

Edited July 15 by AuntiS

[exlimey]

1 hour ago, AuntiS said:

Here in Canada, all our units are K typed by Canadian Blood Services.  It wouldn't necessarily be more work to select K neg units, but we feel it isn't needed.

Just curious.....what does the system do with those potentially immunogenic K+ units (donors) ?

[RichU]

UK units are all K typed. We don't give K+ blood to females <50years, children, anti-CD38 patients, chronically transfused (eg Sickle) or anyone with anti-K. Anyone else is fair game.

[Malcolm Needs ★]

On 7/20/2021 at 2:03 PM, RichU said:

UK units are all K typed. We don't give K+ blood to females <50years, children, anti-CD38 patients, chronically transfused (eg Sickle) or anyone with anti-K. Anyone else is fair game.

Well, unless they are K+k- and have made an anti-k!!!!!!!!!

[jojo808]

I need clarification. I once asked on this site that if you could not rule out an antibody could you 'ignore' it once your screen is negative and I believe the answer was no. If in these cases with Patient's going off Daratumumab, if you could not rule out Kell (due to DTT treatment of cells), even once, don't you have to consider that a permanent problem even though  we know that the probability that an allo anti-K developed is probably null? 

[RichU]

I think it depends on individual circumstances. I would not keep K- units as a requirement for these patients once therapy has ended and no antibodies are detected.

I would always give c-, E- units to an R1R1 patient with anti-c whether or not anti-E had been detected.

@Malcolm - as I've said before, there are always caveats with serology! (even that statement)

[Ensis01]

On 8/19/2021 at 3:44 AM, jojo808 said:

I need clarification. I once asked on this site that if you could not rule out an antibody could you 'ignore' it once your screen is negative and I believe the answer was no. If in these cases with Patient's going off Daratumumab, if you could not rule out Kell (due to DTT treatment of cells), even once, don't you have to consider that a permanent problem even though  we know that the probability that an allo anti-K developed is probably null? 

There is a difference, I believe,  between not being able to rule out an antibody in the context that it may be there, the answer no you state above, and not being able to rule out due to the method limitations (DTT). The DTT method  limitations result in K neg units being given but once the DARA effects wears off a different, more appropriate (and better) method is used so anti-K can be ruled out and the K neg requirement dropped.      

[jojo808]

I don't see the difference. Just because you give Kell neg units due to DTT denaturing Kell antigens, doesn't mean a Kell antibody was never there in that very sample. Is there any way you can prove that? Yeah I know I'm playing the devil's advocate, I really don't want to but if we are saying we can't rule it out, then you have to consider it may have been there right?  

[Malcolm Needs ★]

1 hour ago, jojo808 said:

I don't see the difference. Just because you give Kell neg units due to DTT denaturing Kell antigens, doesn't mean a Kell antibody was never there in that very sample. Is there any way you can prove that? Yeah I know I'm playing the devil's advocate, I really don't want to but if we are saying we can't rule it out, then you have to consider it may have been there right?  

I will also play "Devil's Advocate" then.  Where on Earth are people finding all these units of blood that are Ko (which is what Kell Negative means), and, on the other hand, if you are going to give K-, k+ units, how do you know that the patient isn't a K+k- individual, with an anti-k?  Why not KEL genotype the patients (and I don't mean a full gene sequence) and give "matched-blood" for what the test predicts the antigen expression?

[Neil Blumberg]

We have yet to see a patient on daratumamab who has made an anti-K antibody after years of transfusing red cells without regard to K antigen status.  We use cord red cells in an antibody screen to rule out significant antibodies to allogeneic red cells (they are CD38 negative) as our method of dealing with this issue of pan-reactivity from daratumumab. I know this practice isn't allowed in the UK due to the over the top regulations that followed the infant parts kerfuffle.  We detect plenty of anti-K's, just NOT in patients receiving anti-B cell therapies.  In fact, I cannot recall a single new red cell alloantibody in myeloma or lymphoma patients receiving daratumumaub, rituximab, etc.  No B cells equals dramatically reduced risk of alloimmunization, so you may be worrying about something that is pretty unlikely to happen.  Just another approach.

[Malcolm Needs ★]

2 hours ago, Neil Blumberg said:

I know this practice isn't allowed in the UK due to the over the top regulations that followed the infant parts kerfuffle.

Oh, how agree with your comment.  Mind you, it must be remembered that this was all caused by doctors (mostly histologists, if I remember correctly) who kept parts of babies, without asking for the permission (or telling) the bereaved parents.

[Neil Blumberg]

Malcolm, I agree this was truly insensitive and arrogant behavior, not atypical of physicians in many periods of history, granted.  I do believe this is very different from our use of about to be discarded cord blood specimens used for laboratory testing, but I'm sure some would disagree.  Our human subjects review boards generally consider laboratory testing blood specimens from patients that would otherwise be discarded may be used for research purposes or quality control purposes without informed consent.

[jojo808]

I understand now, had to read the thread over again and the reasoning with my simple mind.  Well if the patient's antibody screen was negative prior to Darzalex treatment, then given K neg units once the antibody screen was affected by the DTT technique, then I can understand how giving 'regular' units once the antibody screen is negative would be acceptable because none of the units given would have caused that immune response (Aha moment).  duh. Thanks everyone.

[Malcolm Needs ★]

14 hours ago, Neil Blumberg said:

Malcolm, I agree this was truly insensitive and arrogant behavior, not atypical of physicians in many periods of history, granted.  I do believe this is very different from our use of about to be discarded cord blood specimens used for laboratory testing, but I'm sure some would disagree.  Our human subjects review boards generally consider laboratory testing blood specimens from patients that would otherwise be discarded may be used for research purposes or quality control purposes without informed consent.

I agree entirely.  I found it really difficult sometimes, when, for some reason best known to themselves, a Blood Transfusion Consultant in a Hospital would insist that we performed a titre and/or a specificity on a cold auto-antibody, rather than just the thermal amplitude (as advised by Petz and Garratty), and I had forage around in our freezer for extremely rare Adult ii red cells, rather than using an otherwise discarded cord sample.  It is utter madness.

[AuntiS]

On 7/15/2021 at 10:32 AM, exlimey said:

Just curious.....what does the system do with those potentially immunogenic K+ units (donors) ?

Sorry - just saw this reply now.

Canadian Blood Services tests all donor units for K.  If K negative, the donor end label has K- on it.  If K positive, the end label doesn't have any K antigen testing information listed - the K+ status is only embedded in the donor unit phenotype barcode.

All donor units are treated the same - so the K+ units are available, as all other units are, but it is easy to select a K- unit for females of childbearing potential and who are on a drug like daratumumab.  

sandra

[exlimey]

On 9/15/2021 at 8:08 AM, AuntiS said:

Sorry - just saw this reply now.

Canadian Blood Services tests all donor units for K.  If K negative, the donor end label has K- on it.  If K positive, the end label doesn't have any K antigen testing information listed - the K+ status is only embedded in the donor unit phenotype barcode.

All donor units are treated the same - so the K+ units are available, as all other units are, but it is easy to select a K- unit for females of childbearing potential and who are on a drug like daratumumab.  

sandra

Thanks, Sandra. As I'm sure you knew, I am aware of the answer - no way, no how are blood suppliers going to "discard" ~10% of their product. But I think it's important to consider the consequences of some of the now routine testing algorithms. No testing mean results are unknown, but once one has information, one may be required to take action. Many transfusion protocols for chronic users involve Rh (C/E) and K matching - there's another batch of donors whose (partial) phenotype is known and considered to be quite immunogenic. It goes on.

I do find it interesting that your system "hides" the K+ status, but openly prints the K- attribute on the label.

Another thought: If the K type of all of the patients were known, they could get the K+ units. The antigen frequencies should match up.