I would really like to talk more about SLL, being that is what I initially had and still have. But it has been made a subgroup of CLL, because once the cancer spreads to the blood, and is no longer just in the lymph nodes, it is considers lymphoma/leukemia (SLL/CLL). Even though I actually have a lymphoma cancer, in the same group as Non-hodgkins lymphoma, the testing and chemotherapy is now the same as CLL(Chronic Lymphocytic Leukemia). So I thought instead, I would inform my SLL/CLL partners and their loved ones, some information about what can and usually kills us, and hopefully how we can resist these results, at least for a while.

The following article was written by Chaya Venkat, written last May, and I have updated its contents to show the current status of the trial.

The single biggest killer of CLL patients is uncontrolled infection – most often, pneumonia.  Adding insult to injury, routine vaccinations do not work very well for us.  Secondary cancers such as skin cancer could also be due to inadequate immune protection. Getting a clear understanding of immune dysfunction baked into the cake for us is the first step in perhaps protecting ourselves better. This is an important subject, so if you are reading this, and know someone with SLL/CLL, please let them know, what is written here. There is new information and a new, clinical trial, announced May 10, 2011, and as of Sept, 2011 has started recruiting participants. There is no way of making a sound bite of this topic and only you can do the heavy lifting of actually reading this admittedly long review carefully, and deciding for yourself whether you agree with the logic. I promise you the effort is worth it. The trial you will be looking for is NCT01351896.

Many things contribute to poor immune defenses for us. Before I get to the main course, lets count the many different ways we are vulnerable to infections – especially viral infections. You cannot fight an enemy you do not understand.

First and foremost, CLL is a cancer of the very immune system that is supposed to protect us – it is like a police department that allows criminals to flourish unchecked. It is true that CLL is a cancer of the B-cells but that is only one part of the immune system. There is a lot of interaction between the various arms of the immune system, that given enough time, the cancer will spread everywhere. This is particularly true of B-cells and T-cells, partners that have many interactions. The net result is that many of us have deeply compromised immune function across all aspects of our immune defenses. This is particularly true of advanced cases and those that have already been through immune suppressive chemotherapy regimens.

Age is also an important factor, and there is no denying the majority of us are in our sixties, seventies or older. One of the consequences of aging is a drop in both the number and diversity of T-cells, and since T-cells are the most important front-line troops as far as viral infections are concerned, this means older patients are more at risk of viral attack. As we age, and T-cell counts drop, so too do their ability to secrete very important proteins called cytokines. In particular, two specific ones called interleukin-2 and interferon gamma (IL-2, IFN-gamma). Low levels of these two cytokines is the hallmark of the frail elderly, prone to infections person.

No matter how fit you are or how young you look, (and I look young (ha,ha), well my wife says I do, so there), there are some aspects of aging that are unavoidable. One of them is the health of your thymus. This little gland is located just behind the sternum, below your thyroid gland. At birth it is about 5 cm long and reaches its maximum weight (20-40 grams) by the time of puberty. The thymus is at its most active during  pre-adolescent period. By the early teens, the thymus has already started to shrink (“atrophy”). By the time you reach 75 years, it is a mere shadow of its former self, weighing only 6 grams. Why is this important? A healthy thymus is not just important but pretty near critical to the health of your T-cells. You see, newly minted T-cells are not very smart, something like little babies, not to smart and need a lot of teaching. They have no idea what to attack, how to tell the difference between friend and foe. They get their education and become “smart” at only one location in the body: your thymus. In fact, these cells are named “T“-cells because they get their marching orders during their stay in the Thymus (get it, T for thymus). As the thymus decays, so too does the ability of this glad to train new generations of T-cells. It is no coincidence that as people get older, they are more prone to viral infections, autoimmune disease, even cancer – all of which are a direct consequence of poor T-cell function.

Can drugs take over where our bodies and T-cells fail us?  Not when the infections are due to viral invaders. Unlike bacterial infections, viral infections are harder to treat. We have available to us a huge line-up of broad spectrum antibiotics and with the exception of a few multi-drug resistant bacteria (MRSA and NDM-1 are good examples)  it is possible to hit bacterial infections with a heavy-duty shotgun approach that is quite effective. Not so if the infection is caused by a virus. PLEASE understand antibiotics do NOT work on viral infections. As of today, we have only a few very specific anti-viral drugs. None of them are truly broad spectrum and more often than we would wish it is impossible to even identify the real viral culprit soon enough to treat the patient. Nothing we have invented by way of drug discovery comes close to the job that a large and well-educated army of T-cells can do.

One of the most important methods of defending against viral infections is active vaccinations.  Basically, a small and de-fanged (meaning not dangerous)  piece of the virus in question (say, the annual flu virus) is introduced into our bodies. The hope is that seeing this dangerous looking bit of a virus our bodies go on high red alert mode, beefing up resources to fight the actual virus should it ever invade our bodies. This is what is meant by the phrase “mounting a response to vaccination”. Unfortunately, older people and especially immune compromised folks like us are unable to respond sufficiently to vaccinations and mount a robust response. We just don’t have what it takes by way of T-cells (among others) to get the ball rolling! It is now well understood that CLL patients have less than effective response to annual flu shots or periodic pneumonia shots, especially if the patient has already undergone chemotherapy.

Last but not least, some of the most potent drugs in our arsenal to fight CLL are also the most dangerous to T-cell health. Fludarabine and Campath (alemtuzumab) are both justly infamous for killing off T-cells. In the case of Campath, it has been clearly documented that T-cell numbers and their diversity take a huge hit that is not reversed any time soon.  T-cell counts are less than 25% of their former levels as much as 9 months after completion of Campath therapy. Is it any wonder that viral infections and viral reactivations are so much more common after Campath and/or fludarabine therapy?

So what can we do about all this? There is no fountain of youth that can turn us back into healthy youngsters with a hefty thymus doing its job of training hordes of new T-cells (or may be there is!? Read on). We don’t really have much control over new viral drug development. True, we can use more commonsense and try to avoid viral infections by practicing “social distancing”, which I find myself doing more and more these days. Are there any drugs out there that will make vaccinations work better for us? CLL Topics sponsored and funded a clinical trial that explored one such approach, call Jab&Stab. Unfortunately, this trial has not gone anywhere and there are no clear results one way or another.

This new clinical trial is hot off the presses, and was announced on May 10, 2011. As I said earlier, it is now open for recruitment, so if you are interested, please explore this option. The NCI (National Cancer Institute) and Ohio State University Hospital are collaborating on this one.  The university (OSU) is the only location where it will be offered.

In a nut-shell, the study involves giving CLL patients pneumonia vaccination shots (PCV13 vaccine) concurrently with low dose lenalidomide therapy.  Say what?  Low dose Revlimid along with pneumonia shots?  How does that compute?  Please click on the clinical trial link to read all the details of exactly how the trial is designed, who is eligible to participate, contact information and so on.

So here is some more good reading for all of you SLL/CLL’ers out there.