Monday, August 29, 2011

Bernie Marini and the Deathly Infections: A Tale of Mudbloods and Unicorns

Posted by Bernie Marini at Monday, August 29, 2011

I know what you're thinking - How did Bernie get so lucky to have a rotation at Hogwarts School of Pharmacy? Although that would explain why I've been so busy and haven't posted yet, I'm not actually enrolled at Hogwarts and my preceptor is not Dumbledore (Dr. Frame is way smarter). However, I have just completed my first rotation with Dr. Frame at the Bone Marrow Transplant unit at U of M, and my rotation has had some strange similarities to the epic series that we've grown up with. If you're not a Harry Potter fan (shame on you), you're probably lost at this point, so I apologize, but... at least you have a good idea of how I felt on the first day of rotation.

Before you start reading about the magic abundant within the world of BMT, I have to drop some knowledge on you. This blew my mind the first day: Although this is the "bone marrow transplant" rotation, they rarely harvest stem cells from the bone marrow these days. That's right, no large needles or painful procedures like you see in the movies. Instead, donor stem cells are obtained from peripheral blood via leukapheresis. To increase the number of circulating stem cells for collection, donors are given agents such as G-CSF, GM-CSF, plerixafor or chemotherapy (typically Cytoxan - obviously this would only be done in autologous transplants) to mobilize the stem cells. The process of donating stem cells is relatively painless, which is why you should join the Be The Match Registry® and save someone's life today!


Yes, Mudbloods, or "MUDs" are a common term in the world of BMT. MUDs are not muggle-born wizards and witches as you've learned from the Harry Potter movies, but are Matched Unrelated Donors, which is one of the four main types of hematopoetic stem cell transplants (HSCTs):

1. Matched Unrelated Donors (MUDs): As the term implies, these stem cells are obtained from non-relatives who are matched at the major HLA antigens (typically they look at HLA-A, B, C, Dq, and Dr). Each person has two alleles for each HLA locus, so the degree of matching is typically reported as a fraction out of 10. If a donor is a 10/10 match for all of these HLA alleles, they are a good candidate for serving as a donor for that particular patient. However, there are many minor antigens, and because the donor and recipient are unrelated, there is a higher incidence of graft-versus-host-disease in these patients, even in 10/10 matches. Simply, GVHD occurs when donor T-cells react to host antigens and mount an immune response against the host. Acute GVHD commonly manifests in the skin, liver and GI tract.

2. Matched Related Donors (MRDs): These transplants are also matched at HLA alleles, and there is less incidence of GVHD, as there will be a better match at the minor antigens, owing to the fact that the host and donor are related. There are also mismatched related donors, but I don't think I need to explain this one.

3. Double Cords: Umbilical Cord-blood transplants are the final type of allogeneic transplant. Cord blood transplants are unique, because patients are actually given stem cells derived from two non-identical umbilical cords. Interestingly, only one cord actually engrafts and "wins out"; however, giving two cords (and a higher number of stem cells) may shorten the time to engraftment and improve outcomes.

4. Autogeneic transplants, or "Autos": The previous three transplant types were allogeneic (donor and host are non-identical) transplants. The primary reason for performing an allogenic transplant is to obtain the seemingly magical "graft-versus-tumor" effect (the donor immune system attacking the tumor in the host). Autogeneic (donor and host are genetically identical) transplants, on the other hand, are performed so that patients can receive very high doses of chemotherapy that would normally completely ablate a persons bone marrow and result in death. Instead, stem cells are harvested, the patient is given super-high-dose chemotherapy, and the stem cells are put back into the patient to rescue them.

The Deathly Infections

In HSCT, the patient's bone marrow is completely wiped out. Thus, patients are neutropenic and without a functional immune system for a significant amount of time post-transplant. As you would expect, infections are very common and can be deadly:

1. Viral Infections: Patients are at an increased risk for reactivation of latent virus and de novo viral infections. Common viral infections in HSCT patients include CMV, HSV, VZV, HHV6 and BK virus. Treatment for these infections often involves antivirals with serious side effects, including ganciclovir, cidofovir, foscarnet, and many others.

2. Fungal Infections: These can be particularly deadly, especially if not treated right away. Usual suspects include candida, aspergillus, MUCOR (coolest name ever, this fungus is bad-news-bears!), and fusarium. On a CT, you would typically see a "halo sign", because invasive fungal infections such as aspergillus love to invade the surrounding vasculature and the "halo sign" you see is actually the bleeding around the fungal nodule.

3. Bacterial Infections: Besides the usual suspects in febrile neutropenia - coagulase-negative staph is the most common - we have seen some very unusual infections on the unit this month. We've had an acid-fast, non-mycobacterial infection (possibly nocardia!) and C-Difficile sepsis!


Because our last day was Garret's birthday, Dr. Frame made us a Unicorn cake! Why a unicorn cake you ask? Well, my daughter had her 4th birthday party this month, and it was a "Unicorn" party. We were toying with the idea of making Garret a unicorn cake for his birthday as well, but didn't have the artistic ability to do it. It's a good thing Dr. Frame, besides being a tremendous preceptor, is also an expert cake decorator.

Well, that's all I've got for the amazing world of HSCT. If you have any questions, drop them in the comments section, and I'll be happy to answer (Although I don't think I've ever seen a single comment in any of the P4 blog posts). It's been a difficult but rewarding month. As a BMT pharmacist, you truly have to be an expert in EVERYTHING - ID, Heme/Onc, you name it. However, the success stories are truly amazing. Many of the nurses on the unit wear shirts that say "BMT: Believe in the Miracle of Transplant." However, in the spirit of the Harry Potter series, they should read "BMT: Believe in the Magic of Transplant"

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