More Pills Than Seems Reasonable

Day +17 post transplant, and the living is easy – that is, if you are completely ‘anal’ about keeping on top of all the medications needed to keep the post transplant patient healthy and happy. I am not kidding, the list of medications that Harvey needs is pretty impressive and reinforces once more the need for a very detail oriented caregiver. Below is the list of medications and the logic for taking each of them. I refrain from giving you dosages, since they depend on the individual patient and the treating institution.

  1. Anti-rejection, anti-GVHD drugs: the two mainstays are MMF (mycophenolate mofetil, brand name “CellCept“) and CSA (cyclosporine A, brand name “Gengraf“). Both of these essential medications are taken twice a day, in hefty doses. The idea is to put the brakes on the old and new immune systems, the former to prevent rejection of the graft and the latter to prevent over the top acute GVHD. Cyclosporine levels in the blood vary between patients even when they are given the same oral dose. Hence, the hospital measures the blood concentration of CSA and modifies the dosage to maintain the level within required upper and lower limits. I am told the MMF will be tapered off by the end of the month. Not so the CSA, Harvey will be taking this for 6 or more months, depending upon his GVHD and GVL status.
  2. Prophylactic medications: the usual triumvirate of anti-bacterial, anti-viral and anti-fungal (levaquin, acyclovir, fluconazole) are mandatory. If the patient is considered at risk of CMV reactivation (I have more to say about that below), the acyclovir is administered at a truly “manly” dose.
  3. Growth factor support: Harvey gets daily shots of GCSF (granulocyte colony stimulating factor, trade name “Neupogen”) to encourage production of neutrophils, the front line defending troops against infections. Protocols differ on how Neupogen is used. U of M in this double cord transplant protocol requires daily Neupogen shots until the patient has achieved ANC (absolute neutrophil count) of 2.5K and can keep it there for at least 2 days running without help from Neupogen shots.
  4. Electrolytes: magnesium and potassium are very important electrolytes that can get depleted because of the various drugs used. CSA is particularly bad on depleting magnesium levels. Harvey’s electrolyte levels are checked each day and if the magnesium levels are a tad low (in spite of the many magnesium oxide pills he takes each day), he gets an iv bag of magnesium sulfate to bring him up to spec.
  5. Vitamins: believe it or not, they did not have this on the list of medications. We had to ask about it before they added it in. In view of the somewhat limited food choices that Harvey is making these days, I am not convinced he is getting all the vitamins he needs for good health from his diet. They sounded a little taken aback when I asked about him getting a daily multivitamin. I guess they are more used to worrying about larger life threatening issues with their post transplant patients, multivitamin supplement is low on their radar screen.
  6. Liver protection: with all of the drugs that transplant patients need, there is increased load on the liver, the major organ that gets involved in disposal of toxic waste. “Ursodiol” is an interesting drug that I am told comes from the bile salts of bears (hence the name, Ursa means bear in Latin). It seems to a wonderful job on helping the liver, Harvey’s lifer enzymes (ALT, AST) have never been better.
  7. Antacid: With switching to oral pills, there is always the issue of the stomach rebelling at the fistfulls of less than tasty little buggers. Hence the need for pantoprazole (trade name “Protonix“).
  8. Anti-nausea: chemotherapy is frequently accompanied by nausea, making it hard for patients to eat well and thereby keep up their strength. Harvey never carried around a lot of extra weight, he was a svelte 64kg (141lb) before checking into the hospital and he is now 61.6kg (135.8 lb). Five pound weight loss that shows itself in a thinner face, tightened belt. The drug of choice for chemo-induced nausea is lorazepam (brand name “Ativan“). While in the hospital Harvey was getting 0.5mg of the stuff injected into his iv every two hours. Now that he is home, he is given a bottle of the tiny white pills and told to take them “as needed”

Well, since his nausea was under better control, Harvey decided to skip some of the Ativan pills – and all hell broke loose. In a very short period of time he went from a nicely chilled out guy feeling good about the world and himself to this cranky, agitated and confused individual that felt miserably cold no matter how many blankets we piled on him. Talk about your classic drug withdrawal symptoms! Fortunately we had two laptops fired up and ready to search for answers at a moment’s notice. It was not all that hard learning about the withdrawal symptoms of Ativan. Believe you me, it is not a good idea to stop taking this drug ‘cold turkey’. After the fact, when we asked the doctors about it today, we were told that many patients become ‘addicted’ to this drug to some extent, and there is nothing to do but wean them off gradually to minimize acute withdrawal. Drug withdrawal on top of everything else – hardly seems fair, but the darn drug does work well in controlling post chemo nausea so we are happy Harvey had access to it when he needed it. Now we are going to get him off of it ever so slowly.

With a Little Help From Generous Donors

Yesterday, for the first time, Harvey got red blood cell and platelet transfusions. His hemoglobin had tanked to 8.2 and coupled with low blood pressure (he needed to increase his liquid intake), he was about ready to keel over, especially if he stood up quickly. So the hospital waived its rule of 8.0 hemoglobin as the trigger point for red blood cell infusion and went ahead with 2 units of red blood cells. His hemoglobin today is a healthier 10.7 and we opted to walk to and from the clinic, rather than taking the shuttle service. Platelets too bounced from 13K to 25K. Not bad at all.

Checking into the whole issue of CMV status of blood products, I have some information to report. ALL, repeat, ALL transplant patients must get only irradiated blood products. This is good first line defence against getting any unwanted hitchhikers in the blood products transfused. If there is specific concerns about CMV transmission from the blood product to an otherwise CMV seronegative patient, additional precautions must be taken. These days they use “leukocyte reduced” blood to cover much of the risk of CMV transmission. Leukocyte reduction means the blood is ‘filtered’ to remove most if not all of the leukocytes in it (leukocytes, aka white blood cells, includes B-cells, T-cells and neutrophils). It turns out traces of CMV reside in neutrophils and getting rid of these pesky cells in the red blood cell and platelet transfusions removes the risk of transmitting CMV to patients. Here is an authoritative link on the subject and a recent PubMed abstract that highlights the growing popularity of leukocyte reduced blood products for transfusions.

Clin Infect Dis. 2007 Oct 15;45(8):1008-13. Epub 2007 Sep 6.
Leukocyte reduction’s role in the attenuation of infection risks among transfusion recipients.
Cervia JS, Wenz B, Ortolano GA.
Pall Medical, East Hills, NY 11548.

Despite advances in the screening of donated blood for infectious agents, the risk of transmitting viral, bacterial, and protozoal infections, as well as newly emerging diseases, via transfusion persists. A complementary approach is leukocyte reduction (LR), the removal of leukocytes from donated blood by filtration. Published evidence, establishing the benefit of LR in reducing the risk of febrile nonhemolytic reactions, cytomegalovirus transmission, and human leukocyte antigen alloimmunization has led to its use for some time for the care of immunosuppressed and other individuals considered to be at high risk for such complications. Recent literature suggests that LR may be effective in reducing the risk of transmission of a number of additional transfusion-transmitted infectious agents, including herpesviruses, retroviruses, bacteria, protozoa, and prions. There is also evidence that LR may reduce the risk of transfusion-related immunomodulation, further contributing to protection against infections that would complicate treatment. With the mounting evidence of potential benefit, a number of countries, as well as many hospitals and blood centers in the United States, have adopted a policy of performing LR for all donated blood. Physicians who care for immunosuppressed patients and those who are responsible for institutional infection-control practices should remain informed of the growing body of literature on LR.
PMID: 17879916

Harvey started with a B+ blood type prior to his transplant and the two cords infused were B- and O+. At some point when he is fully engrafted he will switch from his prior B+ status to the blood type of whichever cord wins the ultimate battle for survival. Right now, he has possibly a mix of all three blood types. (We are calling him “Harvey, One of Three”, tertiary adjunct of unimatrix 01, a reference you will not get unless you are a Star Trek fan and know all about Borg naming practices). As you would guess, the transfusions he gets must therefore be of the blood type O-, the universal donor that works for all blood types. Once it is all sorted out, he can start getting whatever blood type he turns out to have at that time.

The moral of the story, at least as I read it: if you are a CLL patient (more importantly so if you are a transplant patient) and therefore dependent on getting multiple blood product transfusions, it makes sense to know your blood type and your CMV status. I see no reason why any of our guys should ever get less than irradiated blood. If you are CMV sero-negative to begin with (chances of that are low, since close to 80-90% of the population is CMV positive), you should also insist on “leukocyte reduced” blood. My guess is this would also work for EBV sero-negative patients looking to stay this way. EBV resides in B-cells and removing traces of B-cells in the red blood cell transfusions will limit the risk of unwanted EBV transmission. Even if you are EBV and CMV positive to begin with, this level of precaution is probably a good thing. As the abstract we quoted above points out, there are multiple benefits of using leukocyte reduced blood products. As an immune compromised CLL patient will you routinely get irradiated, leukocyte reduced blood even if you did not ask for it? Call me a cynic, I do not think this happens all the time. As always, since you are the one with more skin in this game, it is to your advantage if you keep an eye on what goes into your body and that means insisting on irradiated and leukocyte reduced blood products only. Just a word to the wise.

Be well,