A rough day: Bloody nose times two and a tender rash minutes before my CLL and MDS lectures in Chicago

I am all better now, but yesterday after finally catching up on some desperately needed sleep in my Chicago hotel, in the bathroom in the morning, I had a nasty sudden bloody nose that wouldn't stop until I applied 20 minutes of direct pressure with both hands.

It was reassuring to know that my platelets had just been checked the day before at OSU in Columbus and were nearly 400,000 so I knew it wasn't my ITP returning, but could it be some platelet dysfunction related to one of the many meds that I was taking? Use of coumadin excludes you from an ibrutinib trial due to possible increased bleeding risks, but was there a concern if you weren't on a blood thinner? Aspirin and other anti-platelet drugs are OK so the concern may be very specific. Being the information hound that I am, I reviewed some old articles on the subject. A study in Blood (2000) looked at the platelets in patients with XLA (an X linked congenital lack of BTK) suggested "These results suggest either that the Btk/Tec family kinase activity is dispensable to platelet function or that there is sufficient Btk/Tec kinase functional redundancy to rescue signaling in specific receptor pathways." In other words, BTK inhibition may have some effect on platelet function, but it is not critical. Another article in the same journal (2006) states: "In summary, the data presented here demonstrate the previously undocumented and critical role of Btk in bt/VWF-induced signaling in vitro and GPIb-dependent stable thrombus formation in vivo." This seems to suggest BTK may play a significant role in proper platelet function. Current Biology in 1998 concludes: "Our results demonstrate that Btk is important for collagen signaling via GPVI, but is not essential for thrombin-mediated platelet activation." I don't pretend to understand all the nuances of these reports, all of which are several years old and predate the era of BTK inhibitors and none of which were studying ibrutinib or any other BTK inhibitors. Rather, they were looking at the platelets of patients born without BTK. Still the data seems to suggest there is a definite role for BTK in clot formation. However,  I am not sure that it is clinically important as there are also clearly redundant pathways and signaling to get a healthy thrombus going in response to an arterial injury. 

Every trial visit I am asked about nosebleeds and bruising, so there must a need for some vigilance. But then again I am also asked about a myriad of other possible problems. That's why we do trials, to find out the benefits, and the risks.

I had no other worrisome bruising or bleeding issues, so I practiced my own advice and tried to under react.

After the bleeding finally slowed down, I needed to rush to clean up, shower and dress in a a blood red sweater and black jeans to give my CME lecture on MDS (myelodysplastic syndrome) to about 250 primary care providers in Chicago.

It all went well, but I had to fight the urge to sneeze more than once while on the stage.

My day wasn't done. The next speaker in the line-up, a good friend who is an expert in dementia wasn't feeling that well with stomach issues and asked if I could hang around and perhaps switch times with him and go on in his slot. As it worked out, he spoke as planned, so I went upstairs to my hotel room to rest and to quickly email Dr. Byrd who quite sensibly blamed the dry air of the plane and the hotel heating system and not the meds. He did not think it was a significant issue. Further reassured, I took a very short power nap, woke up early for my CLL lecture with a second milder more easily controlled bloody nose and just made it down to the stage for my final 90 minute presentation.

Ironically, the lecturer-friend on dementia who was at the podium between my two talks had to briefly leave the stage because of his gut issues and the moderator needed to jump in with the save. Fortunately Alzheimer's Dementia was one of her areas of expertise. She however warned me I was on my own, as she was not prepared to talk on CLL if I exited the stage with a Kleenex pressed against my nose.

The lecture was uneventful and well received and I hung around to answer questions including one from a doctor whose husband is enrolling in an ibrutinib trial. Today I am feeling fine. A tender mysterious rash came and went on my nose last night (maybe from all that pinching to control the bleeding), but I have had no other issues.


A bloody nose can be a harbinger of trouble or a false alarm, but in either case, it is startling, annoying, messy and inconvenient. It all made for a dramatic and stressful day, but all's well that ends well and it was ultimately of no consequence. If Dr. Byrd isn't worried about a bleeding issue, either am I.

Still I will be glad to be home tomorrow.

Labs were just great at OSU. My counts are all essentially normal on ibrutinib. No nodes to be felt. Anywhere. Like the vast majority of patients, I am responding well. Without a CT scan or bone marrow biopsy, you could not tell that I have CLL. And maybe soon, even those won't show any evidence of my evil clone.

I will soon be reporting on important issues from the Lymphoma Research Foundation Meeting that took place in Manhattan Beach last week, and I will be going to ASH this year, so watch for some newsy posts soon.

Don't do anything RASH

First day of ofatumumab at OSU, so I only received the amazing slow test dose, still I was there almost 12 hours. They are very diligent and careful. Turns out it was a wise precaution.

The staff were all sweet and professional. Couldn't have been nicer.

The fun really began when I broke out in a itchy hive like rash (worse they have ever seen) from head to toe about 4 hours into the infusion when I reached the maximum dose. This was despite the pre-meds consisting of 20 mg of Decadron (a hefty dose of a quick acting steroid), Pepcid (used in this case to block the histamine 2 or H2 receptors), Zyrtec (another antihistamine), Tylenol and 50 mg IV push of the first generation OTC antihistamine/sleeping pill Benadryl (enough to push me straight into la-la land). So it wasn't until I woke up to use the restroom and looked in the mirror that I saw my most impressive splotchy red face and neck. By that time the rash was everywhere. I called my nurse and they immediately stopped the IV and soon I was the hapless recipient of yet another 50 mg stupefying dose of Benadryl IV push and the amped up supercharged power of 50 mg of Solucortef (another quick acting steroid). 30 minutes later the rash was history, the IV restarted. I finished treatment without a hitch around 7:30 PM.

Ofatumumab causes more reactions because it a more active antibody so I can't complain,

Still all the Benadryl will make me sleepy stupid for the next several hours and all the steroids will keep me alert and ready for action all night for the next day or two. Then the crash until my adrenals recover. My body is a little confused as to what to do next.

Another minor issue: I will not be able to tell immediately when my nodes shrink if is it from the wallop of the steroids or the ofatumumab and besides I am way too dopey to think about it.

Finally before all this started, my eosinophils were really high about 2.500 and even appeared in excess in my marrow. More on that when my mind is clearer. More on other lab later too.

Still not a bad day. Got through the test dose. Found the way to the center despite the rain and the construction and the lack of sleep. found a place to park, met nice people, signed onto their patient portal. got my blood and IV with one poke, and dozed for hours.

And this may just be wishful thinking (or the steroids), but I do believe that my nodes are already smaller.

So despite this still not being a therapeutic dose, this is the official star, my first cycle of my next amazing CLL adventure. And its in the bag or should say out of th bag and in me now.

Let the games begins.

Between Barium

The hospital has Internet connection, so between glugs of lovely barium, I can finally detail the story of my rash

I started my cyclosporin(e) last Friday night. Twice a day, a hefty dose.

Also started raw unrefined organic sesame oil to help the platelets Saturday night.

Sunday morning I took my morning meds, but because the cyclosporin was still in its bulky packaging (it takes a few minutes to open the annoying people proof single dose packaging six times) was downstair, it was not part of my usual AM ritual.

Good thing.

Ten minutes later after my usual meds, but with no morning dose of cyclosporin aboard, I felt a sudden flush, my face, neck, back of my hand, upper chest and upper back turned red with a measles like rash, slightly raised, but not itchy.

Very dramatic looking, but two hours later it was all gone. I looked good enough to visit a friend in hospital facing a transplant.

But first I needed to sort this out.

If this was a reaction to the cyclosporin the day before, then I was in trouble. Suddenly, my caution in setting up my plans a step ahead was playing catchup, and I needed to think fast.

I did not want to stop this new again magic bullet that saved me from a death spiral with platelets failing multiple interventions and in the process, offering the completely unexpected bonus of shrinking my nodes to where they couldn't be felt, normalizing my white count and reducing the CLL clone from 90% of my bone marrow to 3%.

The combination with rituximab was the platform on which my transplant was built. There are issues with that, but that is an old story that I have wailed about in past posts.

Taking cyclosporin off the table would be bad news. I needed it in my armamentarium.

So I took it. I took with it no antihistamine before so as not to suppress a reaction. I needed to know, and didn't want a Benadryl covering up a problem.

If it was an IgE mediated reaction, I could be looking at an anaphylactic reaction- shock and awe - with swelling in the throat, wheezing, and rapidly dropping blood pressure.

The only precaution I took was to instruct my wife in the signs of a serious immediate reaction. She knew which meds I should take, and whom to call- 911.

I took the leap, swallowed the 6 pills, and had my wife check on me every few minutes

Foolhardy? You decide.

Necessary. I sure think so.

As you know by now, I won my gamble. Nothing happened with my repeat challenge.

It was the right decision, but a scary one

Next I worried about taking my regular meds the next morning. Would the rash come back then? Again I got the answer I wanted. No problem.

Sesame is the only remaining untested challenge.

Only later did an allergist tell me that my reaction was probably not to the cyclosporin. The timing wasn't right which is what made me think the risk was probably safe in the first place. No itch was also unusual for a dangerous allergy.

She thought it was possibly a passive allergy from the IVig. Someone of the thousands that donated to make that pooled blood product, which after all is just antibodies, may have been allergic to one of my morning meds.

She also recommended, just to be safe was to get an Epi-Pen and dissolvable Benadryl. Shock therapy. Very dumb of me not to have put that in place myself.

Another later opinion from a dermatologist agreed that the IVig was the cause of my problem, but he thought the mechanism was different. It was an immune mediated idiosyncratic reaction, like the reaction to Amoxicillin in kids with mono. Not a true allergy. Not dangerous. The mono rash is insignificant, and is modulated by atypical T cells, not antibodies. Hey, I got atypical lymphocytes. This makes sense.

That is where I am putting my money. And my blood. I think that's the likely story.

So the plan is to try and get a different brand of IVig next time. And take an antihistamine the night before.

Not out of the woods yet, but all manageable.

Later today I will get my CT done and have the results, and pick up my flow cytometry report.

The back story

Because my IVIG is no longer keeping my platelets in safe territory, I needed to make a next move real quick.

There may be time in the future to figure out why, but it was now time to outrun the lions, and then later start building the fence.

Good that I had my old fall back, cyclosporin and rituximab to help me get my life and platelets back in control. The platelet data on my spreadsheet from 2007 was like a salve to my weary eyes, a steady healthy climb when I started on both drugs from the red single digit dances with death to the healthy smooth sailing of numbers that were above normal for most, but what is expected post splenectomy.

My platelets were strong and stable for over 3 years until the last few weeks, so I decided to revisit the magic of how I got there.

Remember too that the combo also knocked the feet out from under my CLL, cleaning up my bone marrow and shrinking my nodes.

I had seen this decision coming and had sent out a "what if" email.

Drs. Forman and Miklos and Byrd (whom I have never met, but was kind enough to suggest the combination in a life changing, dare I say, life saving, phone call three years ago) and Sharma (who would be trigger man on any move and who would need to carry the bulk of the burden of all the fast decisions) were all aboard and in agreement. How rare is that in the world of CLL? No word from Kipps, and Furman was not so sure. Treatment by consensus or vote. That is patently crazy.

Truth is that using those two meds was the approach I had noodled out and I asked my gurus if it made sense. Even crazier you say.

I also needed to schedule a CT scan to see the tumor load before the rituximab infusion melts the nodes.

Blessed trouble is I think the cyclosporine is already shrinking the nodes. That is the kind of trouble I like.

Then the unanticipated.

I broke out in a bright red rash yesterday morning that could to all the world be a STOP sign for taking more cyclosporin.

I ignored prudence, risked a severe reaction (don't try this at home, but I did after briefing my wife in the signs of shock) and took more and survived. Later a first class allergist and a dermatologist both informed me the rash culprit was probably the IVig, so I won my gamble.

Much more on that later. I need to sleep before my CT tomorrow, but I promised this update.

Tomorrow is huge. Results of the CT and my flow cytometry.

When it rains,.....

It pours.

A rash this morning? Reaction to cyclosporine? Or sesame oil (good for platelets)?

This isn't any fun.

If you need me I will be in the situation room, trying to stem my flow of challenges.

All BP and the prez are dealing with is oil.

More later. Gotta make some decision real soon to sort this out.