Pony

I checked the reference from the ALX148 web site and it is bound to an IgG1 frame so the lack of anti-IgG4 in the Immucor -IgG reagents is not going to work. ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile. Kauder SE1, Kuo TC1, Harrabi O1, Chen A1, Sangalang E1, Doyle L1, Rocha SS1, Bollini S1, Han B1, Sim J1, Pons J1, Wan HI1. Author information Abstract CD47 is a widely expressed cell surface protein that functions as an immune checkpoint in cancer. When expressed by tumor cells, CD47 can bind SIRPα on myeloid cells, leading to suppression of tumor cell phagocytosis and other innate immune functions. CD47-SIRPα signaling has also been implicated in the suppression of adaptive antitumor responses, but the relevant cellular functions have yet to be elucidated. Therapeutic blockade of the CD47 pathway may stimulate antitumor immunity and improve cancer therapy. To this end, a novel CD47-blocking molecule, ALX148, was generated by fusing a modified SIRPα D1 domain to an inactive human IgG1 Fc. ALX148 binds CD47 from multiple species with high affinity, inhibits wild type SIRPα binding, and enhances phagocytosis of tumor cells by macrophages. ALX148 has no effect on normal human blood cells in vitro or on blood cell parameters in rodent and non-human primate studies. Across several murine tumor xenograft models, ALX148 enhanced the antitumor activity of different targeted antitumor antibodies. Additionally, ALX148 enhanced the antitumor activity of multiple immunotherapeutic antibodies in syngeneic tumor models. These studies revealed that CD47 blockade with ALX148 induces multiple responses that bridge innate and adaptive immunity. ALX148 stimulates antitumor properties of innate immune cells by promoting dendritic cell activation, macrophage phagocytosis, and a shift of tumor-associated macrophages toward an inflammatory phenotype. ALX148 also stimulated the antitumor properties of adaptive immune cells, causing increased T cell effector function, pro-inflammatory cytokine production, and a reduction in the number of suppressive cells within the tumor microenvironment. Taken together, these results show that ALX148 binds and blocks CD47 with high affinity, induces a broad antitumor immune response, and has a favorable safety profile.

Yes, there are regulations for managing controlled documents for all manufacturers. Like Transfusion SOPs, they have to be put in a permanent archive so there is always a record of the instructions given to customers during a specific time period. In the actual packaging area, there is an SOP-guided process for removing and destroying excess old inserts, once the new insert is approved for use. These usually have a "go live" date like other controlled processes.

It will be lovely to see your smiling face Or you can do what I do. Use a picture of yourself when (in your opinion) you looked your best. Mine has to be at least 20yrs old. No sense going too young - then absolutely no one would recognize me . Although..... anonymity has its appeal. Especially after an episode of "foot in mouth"

That's marvelous! What good sense these organizers have in providing a wider range of speakers!! After you've given the talk on Henry, could you share some of it with those of us that can't get to RI ? I'm going to try to get there but you know what budgets are like - one minute you have it and the next it has gone up in smoke

By all means Tricore, please drop them off at your local used books rather than trashing them. I've got the older versions in the library here so I don't need them. They can still be useful reference sources for folks just starting out in Serology. And they are not likely to cause the hernia Peter thought might result from lugging the fourth edition around.

Sorry sweetie! I thought you were already in consulting mode I never thought you'd abandon us. I certainly won't. I'm not sure about assessing but I'll keep up the lecturing, editing, meetings and fun stuff. I've not set a date yet but it will definitely be in the next 5 yrs. Sooner if health limits me but I 'm working on that.

I've got mine with both signatures safe and sound The original sold for around $350USD so I can't imagine anyone dropping under that for a used version when they know there's a market.

Just a matter of being in the right place at the right time. I'm getting ready to bail and Malcolm has retired so just think of all the stuff that is going to happen that you'll see and we'll just audit. Get out to the meetings if you can and talk to the speakers. It's an interesting time to be in this field

Works for me. I'll talk to Laurie Munk at AABB and see if there's a good way to get the word out about a sign-up sheet. And make sure I'm not breaking any association rules.. I hadn't heard about Marion Scott retiring!! I was talking to Jill Storry last week and she told me about attending Geoff's party. It is frightening - everyone I trained with has retired. Of course, a lot of the Canadians could bail at 55 so that's not fair I feel like a dinosaur at AABB. So many new faces! Will keep you posted as I get information

And retired or not, Joyce is still doing technical editing with me for the ARC Immunohematology journal. She's a riot - loves to pull my husband's chain every time I drag him to a meeting with me. Definitely on my list of top serologists I've worked with in any capacity. Malcolm, I agree with you about Geoff's speaking style - like our late George, he's so comfortable doing it and easy to listen to. I was so glad he carried on with the Race and Sanger book. I heard he had a very nice retirement party this past Feb? or Mar? I met Ruth once through Margery Stroup. What a pair!! Living on this side of the pond, we didn't get many chances to actually meet the greats that stayed on your side. The British Invasion of the 70's gave us a huge boost and more opportunities to work up interesting cases. A poll if large enough would give us some clout when trying to scout up sponsors. But I've no idea how to go about that. Maybe a sign-up sheet at the AABB in Orlando? It could be posted near the computer access area and folks could sign for themselves and friends who aren't attending this year. The original book sold for $350 USD I think. If we could keep it in that ballpark maybe more folks could manage? If we could just get an idea of the size of the market... We've got so many generalists that could really use the help but I'm not sure about how to reach them. Any and all suggestions welcome!!!

Well, I tried. As you anticipated Malcolm, Peter doesn't think there is a big enough market for the book to make another printing worthwhile. He was also rather surprised that folks would want it considering how out of date the molecular info is. We have come so far so fast in that area since the book came out. He mentioned that Geoff Daniel's book is more recent and still available. In my opinion Geoff's book is much dryer in tone (still excellent in content) and I'm not sure how well many of the generalists would do with it. Peter's was written with a lighter tone and is much easier to digest. I also asked about finding group(s) willing to contribute to sponsor a printing such as AABB or one of our reagent suppliers. Peter thought that was highly unlikely. Do we have any idea how many copies we could guarantee? I think the whole idea will hang on making it financially feasible. Anyone got any ideas??

Hi guys, I was down to Supply this past weekend and saw the "old guys". They're doing well. I never thought to ask Peter about the 4th edition or if he'd consider a reprint. Linda is doing some great catering and Peter golfs whenever... I can certainly call and find out if there's a chance of resurrecting Montgomery Scientific for one last round. There isn't another reference book with as thorough a grounding in serology. Will let you know what he says

Just to clarify a few misconceptions: 1. Once a package insert change has been approved and new stock is in, IT IS SOP-driven that all old versions are destroyed and not used in new packages. If you ever get 2 packages of the same product with different version inserts - report it immediately to the company. Major labeling booboo! 2. Changes in inserts are marked as changed until the next revision when those changes become what is marked and the previous set become repeated text. You never know how long it can be between product orders so a customer may not get a revised insert until they order the same product 2yrs later. The changes are tied to the revision number and at any point can be identified for lookbacks. 3. Any change in insert must be approved by the FDA as this is a labeling issue and part of the license. This is not a free process. Any company makes sure the change is necessary and cost-effective within their Regulatory budget before making it. So small word change requests to "clarify" in the users' opinion are not likely to happen until the cost, changes and patient testing impacted make sense. 4. The 6 - 12 month timeline is usually correct. as is the large amount printed for cost containment. It really hurts when branding or reagent changes happen and the Materials Management group just ordered a huge number of inserts which must now be destroyed. Hope this helps

Hi Kelli, I'm so excited to hear you are writing an article for Transfusion. Finding time to write is a challenge. I wouldn't worry about a professional reviewer as the Transfusion staff will edit your article to comply with the Transfusion Style Guide. As one of the former Technical Editors for Transfusion, I'm very familliar with the process. The journal's website which you can access through AABB.org, has instructions for authors that will cover how they would like you to organize your paper (Case Review or original work, etc) and the steps for electronic submission of the file once you are ready for the peer review process to start. The peer reviewers are only supposed to look at content and how you drew conclusions from your results. They will submit questions back to you if it is felt there is more explanation or data needed. This is meant to be a supportive, collaborative process so please do not take any of the comments personally. They are meant to help you look good as an author. When content is settled, the technical editing staff for the journal will will work on your paper to make it comply with the Transfusion Style Guide and send you proofs before anything is printed. They do all the heavy work as far as grammar and formatting are concerned. They will make sure your data is presented in the clearest way possible and that your intended message is delivered correctly. You will be involved in the process but not completely responsible for it so don't worry! Any questions or concerns, I'm happy to help.

Folks, You're falling behind the times. (Malcom you're in the clear in the UK) The commentary published in last March in Transfusion has snowballed at every meeting since. AABB, ARC, ABC, Armed Services Blood Program , CAP, and Am College of Ob/Gyn(ACOG) have all come to terms on a recommended workflow for managing any D typing that does not conform to a clear D+. The AABB meeting in Anaheim was loaded with Technical and Scientific presentations to push this agenda. ACOG has devoted an issue of their journal to educate the docs most affected by the change in reporting. (Glory Halelujah) Even the CMS reimbursement and coding was thoroughly discussed. Which is the crux of the matter for those of us working in hospitals. Sure we'd love to know which weak D patient was Type I, 2 or 3 so we could save our RhIg & D- units but at what cost to our operating budget? This is the time for us to take control of a change we won't be able to avoid forever. There is a licensed product on the market but it isn't a perfect fit for what we need now. We need to push back at the manufacturers(tell any sales rep that tries to push molecular testing) We need to tell them we'll look at this IF they design the product we need to identify D genotypes and make it cost effective. Otherwise it would cost us way too much in training, equipment, proficiency and competency programs to manage full genotyping which we don't need. And for some of the smaller hospitals that might use it once or twice a month, totally negates any saving they would see in RhIg and D- blood. If the Powers that Be are pushing this agenda and they do not want serologic weak D testing reinstated, then they need to get with the program and support our concerns. Otherwise D typing will remain the muddled mess on a seesaw that it has been for the last 40yrs. Just my opinion

There has been a lot of conern in my area about inspectors asking for daily panel QC. As is often the case, we need to educate them on the intent of the standard. I verified with AABB Accreditation who also holds deemed status as CLIA and CAP assessors, that the whole issue hangs on the word "detection" There have been a couple of folks in my area cited for this and they challenged it with CAP (who was performing the assessment) and they won. So I wouldn't upset the assessor, just wait and call whoever the inspecting body is and sort it out. By both FDA and AABB we must be able to detect clinically significant antibodies and provide crossmatch compatible units for transfusion. The identification piece is 1) an extention of your screen cells (more of the same manufacturing process); 2) often completed by a reference lab (within or outside of your system) and 3) is not specifically called out by any accrediting body becasue they follow FDA's lead. Sometimes we are such a detail-driven group it is hard to take the step back and look at the bigger picture.

ackkap - Thanks so much for the follow up! I'm so glad to hear the baby is safe. I haven't seen a case like yours in years so it would be very worthwhile to write it up as a case study. ARC's Immunohematology journal would be a good spot to place it. They still publish practical topics for us serologists. Even better, following this woman could be really interesting. Any chance she might get pregnant again? Technically she isn't a candidate for RhIg but in practical terms - might it prevent her converting to IgG? A shot won't hurt her or the baby. Afterall we give it to D+ ITP patients to help boost their platelet count using the competitive binding theory. You will have to keep an eye out to see if this delivery prompts her to convert to IgG. I've never seen one of these past a single pregnancy. Best of Luck!!

Folks, You are forgetting a few points about anti-D and dealing with it in the IgM form or as RhIg. 1. A product called Saline anti-D (and saline versions of -C, -E and -c) was manufactured 40 years ago from donors who made only IgM anti-D and never converted to IgG. As soon as chemically-modified reagents were available for DAT positive samples, the saline product came off the market. The donors were dying of old age (and not easily replaced) and the cost of the reagent was sky high. 2. If the titer at 37C was 8 and then again at IAT, the titer was still 8, there is no additional IgG activity. The binding seen at 37C is most likely due to the IgM and it is not un-binding through the wash process. If there was more antibody bound that could only react when anti-IgG is added, the titer would most likely go up. If the 37C and IAT testing was run in parallel sets of tubes, all you saw at IAT was the IgM causing direct agglutination. 3. Antibodies with a preference for colder temps or those with a low binding co-efficient will probably not stay bound through the washing process. Those are the only IgM antibodies likely to show a higher titer at 37C and a lower titer at IAT. Most examples of anti-D have very good binding co-efficients which is why they can do so much damage in circulation. 4. RhIg, while being an excellent protective measure for D negative women, is just an artifact in pre-transfusion testing. The patient will always be given D negative products anyway! The biggest issue with RhIg, is that while being manufactured from large pools of plasma with all sorts of RBC antibodies, the final product is also a little different depending on individual manufacturer's recipe. The delivery can be IM or IV and that impacts how much and when it will impact the patient's circulation. Given the sensitivity of Capture, it only makes sense that the manufacturer would acknowledge the impossibility of detecting this artificial antibody 100% of the time. Missing it would almost be preferred as it adds no relevant information for crossmatch testing or the fetus. We would like to see the real alloantibodies that could attack any D negative component transfused in our pre-transfusion testing. That all said, I do believe the manufacturer should support their product and be given a chance to investigate this sample to see how or why their products are not reacting as expected. It would be very educational for all of us to hear the outcome of the investigation. Since the FDA inspects all of our manufacturers' customer complaints and product investigations this has to be performed according to SOP, just like any other blood bank procedure. We can't be given a Marketing spiel.

Thanks so much for posting the picture of Marion! She told me was getting the award and I so wished I could "hop the pond" to go. I'm glad she is enjoying her retirement but she is seriously missed over here!

If all your controls and daily QC are performing as expected, there is no reason to take the instrument out of service. As everyone has clearly explained above - often the issue is sample-related or method-dependent. You'll drive yourself crazy trying to figure out how to re-validate an instrument if the only thing that demonstrated unacceptable performance was the one sample

I can give you the "Delores Mallory" explanation to retic separation. We all believed her You have 2 points working in your favour. 1. The patient's retic rate has increased due to their blood loss/ anemia. 2. The dilution of the donor blood which should have a normal retic count at most, produce a very low ratio of transfused retics to patient retics. While you may get an occaisional donor retic, it will not be enough to bias your phenotype results. If you do see a significant mixed field, you can assume it is due to the patient either not reticing or a 50% or more replacement of patient blood volume. And we know harvesting retics after recent, large transfusions, is a risk we often should not take. Particularly when we now have genotyping available. Hope this helps

This has been an ongoing project for J&J since the late 80's. They have never found a buyer that could meet their price. Price is the bottom line for all J&J afiliates and the Diagnostics Division has never met the required profit margin. Blood Bank is a mature market where many of the customers buy on price rather than quality. Still no matter what happens I do not believe the product line will just drop off the market. The other small companies out there may see this as an opportunity to get a bigger foothold in the market. Immucor has bought anyone else of consequence so I can't see them buying the Ortho line. Let's hope wherever the company does end up it is with an investor that will but some money into R&D. We need to keep competion in the market healthy so that we can keep providing better, faster care for our patients.

In relation to making up a pos control when you rarely see an FMH positive test - This is a rosetting screen test based on the presence of D+ cells in a D- mom. You do not need fetal Hb to make up a control. Just mix some ABO compatible D+ cells in with D-. All you need to validate the functionality of the kit is to run a negative (D- cells) a positive(0.03mL D+ in 9.7mL D-) and a strong pos(.5mL D+ + .5mL D-) and run it in parallel with your current method. You can use a weak pos that will represent less than a 30mL bleed but be prepared to see some rosettes. Immucor will provide your first FMH RS kit at no charge so you are not paying for the validation material. The dilutions provided in the guide they provided are fine but a little more complicated than the volumes I've listed above using whole blood. It doesn't matter what version you use. Plus - the new kit is positive IF you see 5 rosettes total after viewing 5 fields. NOT 5 per field. as you can tell, I've been tearing my hair out with this one but I'm sure I've figured it all out now

Since we're on the subject off exclusions and confirming specificity, I have to post yet another pet peeve. These are 2 different processes. The first is exclusion by 1 double dose cell (or # of single dose ). Then looking to see if you have 2+/2-, or as we do in a ref lab 3+/3- to assign specificity. The result of the first step is a list of possibilities that must be confirmed by further consideration and possibly, testing. When you have something as simple as -E or -K, you know you will have the required number of +/- using one panel. But both steps should be performed while keeping an open mind about the possible outcome no matter how simple the case. I had a staff member mistake an anti-Jkb for an anti-E & -K because the E+/K+ cells were the Jk(a-b+) cells. Unfortunate coincidence but due to a preconceived idea of what was most likely and failing to investigate the possible -Jkb further, the patient received 4 units of which 3 were Jk(b+). I know we all have war stories but we should be very clear how we teach antibody identification.

If you really want a tool to support staff or help teach tech how to do rule outs, you'd be better off using Antigen Plus from Rowny Systems. It's exclusion rules are based on the AABB tech Manual or the company can make you a customized version. Rowny has set it up so you get all you panels electronically so saves time and helps prenvent errors. It has warning built in to get the tech's attention when something doesn't meet standards. You still need to know what you're doing and control is always in your hands. Just my opinion! Pony