Herd Immunity and transplant decision

Dr. STEVEN L. WEINREB is a young 52 year old board certified hematologist and oncologist with CLL who recently underwent a hematopoeitic stem cell transplant in an effort to cure his cancer.

What he wrote in his op-ed piece in the New York Times is an important variation on my mantra of us all being in this together. He argues persuasively for the value of everyone eligible getting vaccinated so that all our communities reach the critical mass, passing the threshold for "herd immunity" that protects those like us and newborn and others with weak immune systems who can not protect ourselves.

Please read and share his opinion piece as I have done. This editorial is an essential teaching especially this time of year. I am grateful that he wrote it and that the New York Times published it.

Dr. Weinreb is obviously bright and thoughtful, a big picture kind of guy, which make my musings about his particular circumstances even more intriguing.

What I find so interesting is that the doctor had chosen about three months ago a transplant as his way out of the CLL morass. Knowing none of his circumstances, I am itching to speak with him and pick his brain on why he, as did I, chose the most dangerous of all paths.

Maybe he'd disagree that a transplant is the most dangerous way to go.

I have argued that doing nothing is sometimes the most risky way to go. With a transplant, it's a 50/50 proposition that I am around in 10 years. Without it, I am waiting on a miracle.

Certainly throwing more toxic myelo- and immuno-suppressive chemo that the CLL clone has already proven it can tirelessly chew up and spit out, while our fragile marrow and immune cells take all the collateral damage is not only dangerous but foolish. A potential fatal misdirected drone attack, a self inflected wound. Too many cellular casualties from "friendly fire"can be the deciding factor in our final mortal battles.

But what if those were not his only alternatives?

Does Dr. Weinreb doubt the new miracle cures? Surely as a hematologist, he'd be ahead of the curve on the latest research on PCI-327654 and CAL 101 and GA-101 and lenalidomide and so many more. Did he see the paucity of bone marrow data and the short follow-ups and the infection risks as cautionary flags?

Had he run out of time or patience to wait for the perfect trial or to open his veins to yet another promising cocktail?

Had he been there and done that, tried one of the new pathway blockers or immune modulators and it failed?

Had he already set sail for a transplant in order to grab a new immune system and the treasure was too precious and fleeting to pass up?

Three months can be a life time in the quickly changing world of CLL research these days. Would his choice be different today?

Dr. Weinreb is sensibly not seeing patients right now, a time that I so well remember. I don't have his email address. I will try to reach him by a call to his office or an old school USPS letter, doctor to doctor and see if he might write a guest post here.

One more thing to do that was not on yesterday's to do list.

Happy New Year to all.

We are all in this together. And that is a good thing.

To J Dean and TomD on AIHA, FCR, PCR, and flu shots

Friends, please please please, ask me medical questions only using email, not in the comments as I can not respond to your questions without your email address that I don't have. It is frustrating for all of us

My email is listed on my blog: bkoffmanMD@gmail.com for that purpose.

Remember I can not give medical advice and all my suggestions are only fodder for discussion with your doctors who know you best and must be discussed with them.

J Dean- I see very little advantage in PCR over FCR in terms of AIHA risk. Both P and F are purine analogues with similar toxicities. Both can cause auto-immune problems. P may be a touch safer in terms of auto-immunity but it can and does cause big problems similar to F in terms of wiping out red cells and platelets.

Instead talk to your doctor about HDMP +R (high dose methylprednisilone and rituximab. Or Dr. Rai's protocol of RCD (see study below) or a trial or single agent ofatuzamab.

I don't know enough about the circumstances to give strong advice, but I personally would never ever do PCR after getting bad AIHA from FRC. Never. And I think most CLL experts would agree. Not all, but most. Get a second opinion!

Here is a recent article on RCD

Rituximab, cyclophosphamide and dexamethasone (RCD) effectively target lymphocytes and inhibit autoimmune processes.

Auto-immunehemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) are known complications of CLL.

Dr Rai and his colleges used the follow formulation to treat AIHA in CLL patients.

Rituximab 375 mg/m(2) i.v. infusion given on day 1,

cyclophosphamide 750-1000 mg/m(2) i.v. on day 2 and

dexamethasone 12 mg day 1-7 given every 3 weeks. Response to

treatment was seen in all 20 patients with CLL with AIHA. Median

hemoglobin pre-treatment was 8 g/dL. The median change in

hemoglobin was 5.2 g/dL and the median post-treatment

hemoglobin level was noted to be 13.1 g/dL. Median duration of

response was 22 months.

Fifty percent of evaluable patients converted to Coombs negative with

median duration of response of 41 months vs. 10 months for those

who did not convert.

Steroid-refractory immune thrombocytopenia was present in three

patients and all responded to RCD. There were no hospitalisations or

infections directly related to RCD. RCD is a safe and effective regimen

in the treatment of immune cytopenias associated with CLL.

Source: Leuk Lymphoma. 2009 Apr 23; 1-8

If your doctor is not familiar with these protocols, absolutely you must get a second opinion. In fact you should get a second opinion any way. Sorry to be so emphatic, but in case tou didn't notice, I am worried that PCR may not be the best therapy for your man.

TomD- It seems a bit early for flu shots. I have not been following the CDC weekly reports to see if they are predicting an early flu season, but I worry that a shot in August won't do you much good in February at what might be the height of flu activity.

Two shots, one how and one in six to twelve weeks, is always a possibility as is the experimental use of ranitidine to boost response.

I would go for the higher dose myself, but it is just a best guess. It is supposed to help the elderly with their reduced response to vaccines, so it makes sense it would help us too, but there is no proof.

Good news

The platelet count today was identical to that of two weeks ago, namely a robust 314,000.

Even without my talismen, it stayed way up.

The rest of the blood count was good. Blood chemistries are pending.

Blood pressure is OK, not great, but OK.

My rituximab is scheduled to start next week at 500 mg. per meter squared x 6 weeks.

The plan is to kick the cancer while it's down. Switching my aim from the ITP to the CLL.

Also got my first dTap, that I am sorry to say, did not make my arm a bit sore, suggesting I am not reacting with much of antibody attack to the vaccine. My last dT (tetanus) was ten years ago until yesterday's shot.

That is why I am trying to procure the high dose flu vaccine, but with my recent rituximab and my CLL, I am not sure even it with a second dose in 6 weeks will help protect me, despite my immunity tweaked by the ranitidine trick of Dr. Hamblin.

This is especially likely since I will be getting rituximab the whole time. It would be best to get the shot before I restart vitamin R, but that may not be possible.

Even the passive immunity of the IVig makes all these important shots less effective. And with just plain old CLL, chances of a good response are dismal from the get go.