The Kindness of Strangers: Getting my IVIG to Control my CLL (chronic lymphocytic leukemia) induced ITP

" I have always depended on the kindness of strangers."

Blanche DuBois from A Streetcar Named Desire

As did Blanche,  I too have depended on the kindness of strangers.

For the last nine years, every few weeks I show up at the cancer infusion center to sit for hours to receive intravenous immune globulin or IVIG. Recently I have stretched the interval between IVs to 7 weeks. 

By mechanisms that are not fully understood, it blocks my stupid auto-immune antibodies from attacking my own platelets that in the past has lead to multiple hospitalizations and fearful encounters with my own mortality when my platelet counts crashed and I was at risk for major bleeds. Thankfully, that is all behind me now.

I  have gradually and cautiously been able to taper off all the other meds for my ITP (immune thrombocytopenia) and my platelets have not fallen. 

Perhaps my ibrutinib helps turn off my auto-immune triggers. As seen in this recent post there is good reason to be hopeful. There are case reports of ACP-196, another promising BTK inhibitor helping too.

Perhaps I no longer need the IVIG, but I am not brave enough to stop it to find out. ITP is scary.

There is another reason not to quit.

My infusion 7 or 8 x year may also protect me from all sorts of infections. And that is important in my work as a doctor and in my fun as a grandfather where I exposed to lots of germs.

Due to the recent measles scare, all the doctors at the hospital where I work were ordered to have blood work to confirm their immunity. I objected for several reasons:

1. I had had measles as a child
2. Due to my CLL, I couldn't take the live vaccine even if my test came back negative.
3. My antibody levels are not my own.

This last one is because of the IVIG that I receive. It is a pooled blood product from 1000s of strangers and by definition contains their antibodies against everything they have either had or been vaccinated against.

No wonder I was immune to everything that I was tested for.

But am I really?

Truth is that it's not me. It is the kindness of strangers' blood that is protecting me. It is known as "passive" immunity as I played no role in forming the antibodies. When the IVIG disappears as measured by the IGG level in my blood dropping after a few weeks as it must, my immunity fades too. IVIG does not boost IGA or IGM, two other important antibody classes, only IGG. 

Compare this to a vaccination where we attempt to mount an "active" immune response that is remembered and always ready to respond. Sadly in CLL, this is usually a barren effort. Flu shots and  other immunizations don't usually work well for us. And we must never risk getting a live vaccine as it might run amok in our bodies due to out immune-incompetence. We are notoriously lousy at making healthy antibodies.

So while I take my IVIG to protect my platelets, it is clearly helping me in other ways.

Thank you kind strangers. Your generous gift of your own blood has touched so many lives that you will never know.

ITP In CLL (Chronic Lymphocytic Leukemia): Personal And Clinical Reflections

Another great discussion courtesy of ONCLIVE with 4 top CLL experts, from left to right: Drs. Byrd, Furman, Ma, and Kipps.

This time they discuss immune thrombocytopenia (immune mediated low platelet count) or ITP.

ITP is where our immune system attacks our platelets. Just our luck, our wimpy inadequate immune system that can't alway respond to an infection or a vaccine or a secondary cancer, whips into high gear to attack its own cells.

In extreme cases it can lead to live threatening bleeding. It is well recognized complication of CLL occurring in < 5% of us, but as the doctors imply, I suspect many mild cases go unrecognized.

When the same process attacks our red blood cells, sometime leading to a dangerous anemia, it is called AIHA for the auto-immune hemolytic anemia. ITP is the platelet version of the same issue. Attacks on the neutrophils and multiple blood cells lineages also occur, but are more rare.

ITP is a subject near and dear to my heart.

About one year after my diagnosis with CLL, I remember being on call for my medical group and waking to the phone in the middle of the night. It was my exchange. I had asked my family doctor to order a CBC that morning because I had noticed some easy bruising and petechiae (tiny red dots caused by small hemorrhages often associated with low platelets) on my legs.

MEDICAL EXCHANGE: Dr. Koffman please.

ME: Yes. It's me.

MEDICAL EXCHANGE: We have a critical lab result ........ on Brian Koffman. A platelet count on 9.

ME: Thanks. I will definitely follow-up on this.

And I did. It was 6 they next morning and I was hospitalized for IVIG and steroids. It bounced up in 48 hours but because of my recurrently dangerously low platelets I would go on to five emergency admissions in the next year,  multiple outpatient infusions, and an urgent laparoscopic splenectomy where I lost half my blood. I failed steroids, rituximab, IVIG, cyclosporin and the splenectomy.

What finally worked post splenectomy was a combination of cyclosporin (an immune suppressing drug used today mostly to prevent rejection of kidney and other transplants) and rituximab that was recommended by Dr. Byrd. The combo's effects were nothing short of amazing, especially  considering that both drugs on their own had had no benefit in raising my counts. On the combo my platelets climbed from single digits to above normal (not uncommon when you have no spleen).

And the combination of cyclosporin and rituximab had the surprising and joyous bonus of reducing my bone marrow involvement with CLL down from 90% to 3%.

There are some case reports in the medical literature of cyclosporin having antileukemic activity, but it generally avoided due to the fact we are already immune suppressed and it can cause significant problems including renal disease, hypertension and aggressive gout.

It was my dangerous and refractory ITP more than my CLL that drove me to a first remission transplant.

That didn't work either, and my ITP was back one year post HSCT.

That were difficult times.

Despite the risks and side effects, it was only about none months ago, after almost two years on ibrutinib and with years of normal platelet counts under my belt, that I finally had the courage to taper off my cyclosporin. I feel it had helped save my life and I worried about stopping it.

But I did and I have done great since.

A few comments from one who's been there and done that. Yes, I know that one case is not data, but it can be a cautionary and instructive tale.

For obvious reason and because it is part of some of the guidelines, I would ask the doctors in the panel to add cyclosporin to their list of second line options for ITP. I would certainly use it well before the extremely immune suppressive alemtuzumab (CAMPATH) that knocks out both T and B cells for a very long time or splenic radiation that has a host of short and long term complications.

I would also remind us all that the surgery does not always go well, though laparoscopic is clearly the way to go. The research tells us that the best predictor of outcome is the experience of the surgeon. Though it didn't work for me, I have no regrets about my surgery.

I would also ask my colleagues to comment on just how difficult it can be to get us off steroids and not have the ITP return.

The data on ibrutinib is encouraging and makes sense from a biological point of view, but it is not 100% effective.

Overall, a very helpful and well considered discussion on a very important and scary topic. As we might expect, while there is much consensus, there is significant polite disagreement on how to proceed.



It is such a blessing to not have to live in fear of what my weekly or twice weekly blood test would reveal.  Showing up at the lab,  not  knowing whether I was OK or I was headed to the hospital.

That's all in my distant past now.

Still, as all of us with cancer know, we are always looking over our shoulder, wary of the return of our past tormentors,

More Good News- Update on My Lab, CT Scans, and General CLL (chronic lymphocytic leukemia) Status

My blog has veered far away from the simple telling of my story to more telling of our stories with much B roll.

I am making plans to maybe bifurcate its content in the future, but for now it will continue its happy and diverse life as a personal health blog, a home for research news and video and audio interviews with leading researchers, and a whole bunch of personal analysis and advocacy on what it all means.

I am back from Ohio State where I am still seeing the research team every 3 months and getting CT scans every six months for my clinical trial on ibrutinib. I have riffed on this being too much radiation before in this prior post that includes links to some of the basic research of radiation exposure and its risks, but Dr. Byrd argues that the few relapses he sees on ibrutinib show up first in the nodes, so he wants to monitor me with the scans.

True enough. When I relapsed post failed hematopoeitic stem cell transplant in 2008, the nodes were my canary in the coal mine showing slight growth months before my lymphocyte counts started to move up and my platelets down.

So twice a year CTs are still the plot line for my clinical trial at OSU.

Since diagnosed in 2005, I have probably had about two dozen CT scans!

Add to that the equivalent of the 20 chest X-rays annually I get from flying over 100,000 miles a year, and my risk of secondary cancer is significant. This link with a NASA produced video tells the air travel part of the story.

If you really want to worry, take a look at this article from Medscape on CT scans in NHL.

But this post is not about the danger of CT scans, but about what my last one showed and happily that was stable disease.

I still have enlarged lymph nodes but they have changed little since October of 2012, or for the last 20 of my total of 25 plus months on ibrutinib. My largest sentinel gut node near my liver was about 10 cm at its peak, 7.3 x 3.3 cm just before starting ibrutinib, 4.4 x 0.7 cm in October, 2012 after about 6 months on the medication, then it shrunk to its shortest 3.9 x 0.7 three months later and when last measured on June 30, 2014 was 4.4 x 0.4 which actually represents its lowest volume. It has been fluctuating and when you account for the difficulty of measuring mobile objects in the mesentery and near the liver, is mostly stable since its dramatic shrinking in the first 6 months of therapy. Its a long hot dog shaped node instead of the more common bean shape. The same early dramatic shrinking in the first six months and slight ups and downs since has been the tale for my other smaller sentinel nodes on the scans.

So I have pretty stable disease.

What does this mean to still have enlarged nodes and a touch of CLL in my blood (see this prior post from last April on my flow cytometry report to understand more about my numbers and disease burden)?

The CLL does not proliferate in our blood, so the disease in our nodes and bone marrow are the source of all our problems and I will ignore the blood for now.

There is good reason to believe that these enlarged nodes are still full of CLL, but that it is not proliferating, thanks to the signal blocking from ibrutinib preventing it from getting the messages from its nurse like cells and others to be fruitful and multiply. So chock full of CLL, but it's dormant.

The other more positive interpretation is that these enlarged nodes are just the scarred down skeletons of the cancerous nodes they once were, and there is no residual disease to be found. Unfortunately, I am skeptical of this more PolyAnna hypothesis, and short of a biopsy which is not going to happen, there is not way to know for sure.

So what to do to avoid waking the Kraken?

Hope my genomic instability as evidenced by my 17p and 11q deletions and my complex karyotype will continue to behave with the ibrutinib aboard and not mutate so that my magical bullet no longer covalently binds BTK and blocks its activity?

Knock down the residual disease by adding a second or even a third agent?

Be reactive or proactive?

That is the question du jour faced by many of us now and more in the future whose CLL is controlled but it is not gone now with the new medications such as ibrutinib and idelalisib.

I have probed this recurring and unanswered question in more detail a prior post, and will soon be updating my thoughts on how to avoid being left stranded on third base and not getting home to a cure.

The rest of my news is also good.

My blood counts are boring and despite dropping my cyclosporin to a token dose of only 25 mgs once a day and stretching my 40 grams of IVIG infusions to every 7-8 weeks, my ITP also remains dormant. I think the possible immune stabilizing activity of ibrutinib and my low disease burden may be the factors  that have given me this long ride with high normal platelet counts. I have not been anemic for many months now and my neutrophils and the rest of the CBC are all copasetic. My blood chemistries are in the normal range and only my very low immunoglobulins, namely IGA, IGM, and IGG give proof to that fact that I still have a B cell leukemia, albeit a very sleepy and well behaved one.

More personal clinical and general CLL news soon, nearly all of it good.

I will be posting some of my interviews from ASCO 2014, plus sharing some exciting advocacy news. Busy times.

Personal Update on my CLL (Chronic Lymphocytic Leukemia): The Good News

It's been a while since I posted on my personal medical news.

Today in Columbus, it was all good. CBC was happily and boringly normal. My Hgb still shows that I am no longer anemic. My ALC (lymphocytes) is 1.4 which is actually a bit high for me, but certainly a comforting level.

My ANC (neutrophils) was healthy. My platelets are a bit higher than normal again, but that is to be expected due my splenectomy. The spleen gleans the aging and decrepit platelets, so counts are higher when it's missing. I will take high platelets any day over the terrors of single digit counts when my ITP was raging. By the way, the accepted wisdom is that the high platelets associated with a splenectomy do not increase the risk of a blood clot, but ironically ITP which ravages the platelets does. You can both hemorrhage and thrombose with the same disease. Seems inflammation is the enemy. I refer you to the 19th century wisdom of Virchow's triad, a trusted nugget carried in the brain of all medical students. 

More on this particular topic soon with some personal revelations, but that is for another post.

My blood chemistries show my liver and kidneys are happy and healthy. The advantages of a vegan lifestyle.

Dr. Byrd would not agree to skipping my next CT scan in three months. The very few late relapses on ibrutinib that he has seen after 24 months (my two year anniversary of living with the TKI magic of ibrutinib aboard will be at 9:30 AM EST on May 7, 2014) are often subtle and begin in the nodes. With my pesky abdominal nodes, that does seem prudent despite my aversion to more diagnostic "radiation therapy". Getting the scan at the newer CT at OSU's Martha Morehouse may cut the rads by as much 60%.

Most relapses occur between 12 and 24 months, so my period of higher risk is thankfully coming to an end. 

Still my clonal instability and my small subclone of 17p deleted cells keeps me forever on alert.

What we really need is a trial for the many patients such as myself that are doing very well on ibrutinib, but are not in a complete remission (CR). How about adding in a PI3K inhibitor such as idelalisib or one of the newer ones following in its footsteps. Hit the cancer clone on two pathways at once. A pincer move. A classic chemotherapy technique, but instead on chemo, we box off the cancer with focused therapies. Next add a potent third generation monoclonal antibody (mAb) such as obinutuzumab once the rascally clonal B cells have been released from the nodes and marrow out into the open spaces of the blood stream where they are easy picking for the antibody. Finally, we add something to mess with Bcl-2, say ABT-199. All this done in a carefully orchestrated and timed dance to maximize efficacy and dodge tumor lysis (TLS) by adding the ABT-199 as the final coup de grâce to make sure the beast will never rise again, but also when the tumor load is low so the risk of TLS is mitigated.

You can't get to cure without first passing by CR and MRD (minimal residual disease) negative.

For me, this is not a theoretical discussion. This is my blood and marrow and proliferative centers in my node that are at stake.

The same applies to many others that are in similar circumstances with ibrutinib and other TKIs.

It may even make long term financial sense in that it may also be a way to limit the duration of therapy with this initial treatment intensification, but with a predicted end of treatment baked into the plan.

I don't want to wait until it's too late so I am hoping such a trial may come to pass, speedily, in my time.  

These and similar concepts are beginning to percolate out there.

What do you think?

I am wondering about bouncing such a plan off the powers that could make it happen. Right now it is a small population that would qualify for such a trial, but our numbers are growing fast.

Please give me your feedback.

"You may say I'm a dreamer, but I am not the only one."

More news, personal and general soon.

I wish a meaningful Passover to all my Jewish friends. May we all leave our personal Pharaohs behind and cross dry shod into the promised land.

IVIG: FDA Demands More Prominent Notification of the Risk of Blood Clots

I get IVIG for my ITP. It used to be every three weeks, but now I have been able to stretch it out to every six and my counts are still great. No one is really sure how it works for ITP, but there are theories that it coats my platelets and protects them from premature destruction. I also enjoy the added benefit of protection against infections.

But it comes with risks. I have discussed some before including infusion reactions and allergies, and renal disease. It is an expensive pooled blood product, so there is always the theoretical risk of an occult infection, but there is such extensive safety measures in place that I don't worry much about that one.

Now the FDA is highlighting the risk of blood clots (thrombosis) in a boxed warning.

Ironically those of us with ITP already have a simultaneously higher risk of both bleeding and clotting. How lucky can you be?

I don't plan to stop getting the infusions, though there is a good chance my ITP is no longer active, but why take the chance. Instead I will try to avoid hopping on a plane the day after an infusion as has been in the case many times in the past. Hydration, being active, and my omega 3 rich diet might also help mitigate risk. So would aspirin, but that's not for me with all my platelet problems in the past.

This is the communication directly from the FDA:

Vaccines, Blood & Biologics FDA Safety Communication: New boxed warning for thrombosis related to human immune globulin products. Date: June 10, 2013 Purpose: FDA has analyzed recent data that has strengthened the association between the use of intravenous, subcutaneous and intramuscular human immune globulin products and the risk of thrombosis. Additional caution regarding the use of these products is warranted. Summary of Safety Issue 1 Recommendations for Patients 2 Recommendations for Health Professionals 3 Summary of Safety Issue The U.S. Food and Drug Administration (FDA) is requiring manufacturers to add information on thrombosis to th current boxed warning in the labels of all intravenous human immune globulin products and to add a boxed warning to the labels of all subcutaneous and intramuscular human immune globulin products to highlight the risk of thrombosis and to add information on its mitigation. A retrospective analysis of data from a large health claims-related database, as well as continued postmarketing adverse event reports of thrombosis have strengthened the evidence for an association between the use of intravenous, subcutaneous, and intramuscular human immune globulin products and the risk of thrombosis. This information necessitates a boxed warning for the entire class of products. Human immune globulin products are used in a variety of conditions, both on and off-label, by healthcare professionals who may not be aware of the thrombosis risk and measures that could be taken to mitigate this risk. Although all human immune globulin products already contain some information related to the risk of thrombosi in the current WARNINGS and PRECAUTIONS sections of their labels, FDA recognizes that the communication of this risk and its mitigation are not standardized. FDA proposes that for thrombosis a more prominent placement of risk information and a uniform approach for communicating the risk and its possible mitigation will help to reduce the occurrence of these serious adverse events. The information on thrombosis in the boxed warning states: Thrombosis may occur regardless of the route of administration. Risk factors include: advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling central vascular catheters, hyperviscosity and cardiovascular risk factors. Thrombosis may occur in the absence of known risk factors. For patients at risk of thrombosis, administer at the minimum concentration available and at the minimum rate of infusion practicable. Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity. Recommendations for Patients Patients should be aware of this risk and discuss this risk with their healthcare professionals. Be aware that thrombosis is associated with human immune globulin products. Talk to your healthcare professional about any risk factors or concerns you may have with human immune globulin products. Contact your healthcare professional if you develop any signs or symptoms of thrombosis during or after receiving human immune globulin. Signs or symptoms of thrombosis may include: pain and/or swelling of an arm or leg with warmth over the affected area discoloration of an arm or leg unexplained shortness of breath

chest pain or discomfort that worsens on deep breathing unexplained rapid pulse
chest pain
numbness or weakness on one side of the body

Recommendations for Healthcare Professionals

Healthcare professionals should be aware of the risk for thrombosis with human immune globulin products and ensure appropriate patient selection and monitoring.
Discuss with your patients the risk of thrombosis associated with these products.
Carefully consider risk factors when selecting patients for treatment with human immune globulin products
Monitor patients carefully for signs and symptoms of thrombosis both at the time of infusion and after infusion and encourage patients to report any signs or symptoms.
Report adverse events involving human immune globulin products to the FDA MedWatch program.

Moving Sideways

Usually boring is the best way to be. No bumps in the road. No drama.

I saw Dr. Kipps last week and with his deeply delving fingers he was able to unearth some cervical nodes that no-one, not even the owner of this body, has ever felt.

But they were all small, less that one by one centimeter and maybe smaller than 90 days ago. When they are that size it is hard to tell if there's been any change.

My counts were still good. The neutrophils were back to normal after the jump up from my burst of methylprednisolone for the fluid behind my right eardrum. My platelets were over 400,000 and my Hgb was 13.8. All good stuff.

The CLL is still there but it is behaving itself. It's pretty stable, moving sideways at worst and more likely improving at a glacial pace.

The only trouble on the horizon is that my right ear is clogged up again. Seems that the steroid fix was only temporary so my family doctor suggested a trial of Afrin. It only helped a little and I needed to stop to avoid the rebound swelling that happens with extended use, so it's time to consult an ENT. I am less worried about it, as it is not progressive, easy to knock back, and mostly just annoying. Still time to check it out and make sure there is no structural problem. He may want to put a ventilation tube in, so I better get my surfing in first.

I am down to one infusion a month of IVIG here, and one more blood draw at OSU. That's more good news as my veins are pretty battered after so many years despite all my efforts to protect them.

Let me give you a sense of some of what I see happening in CLL just with people I know.

In this week alone, I learned that a friend, Chris Dwyer of CLL Canada has developed Richter's Transformation. Heard from another long time CLLer with both AIHA and ITP. After having curative surgery for lung cancer, some else is fighting to get back in the NIH ibrutinib trial which helped her knock back her CLL big time. I had dinner and a wonderful visit with a pal from the east coast who is doing great post transplant at MDACC for both CLL and MDS. Another long time local friend is considering the phase three trial of ibrutinib versus ofatumumab for his relapsed CLL. I said go for it. Talked with a young Asian woman who was diagnosed in her twenties. And this is supposed to be a disease of old white men. And I connected with two CLL widows. Not fair. It's not fair, any of this.

Sometimes the CLL is the least of our problems.

I am back in Ohio in a week. Let me know if you will there too.

L'Shana Tova to all my Jewish friends. May it be a year of peace and good health, May this be the year we see a cure to all cancers.

As for myself, at this time of self reflection and self improvement, I plan to double down of getting the word out about CLL to patients and providers alike.

I will be lecturing on CLL in Las Vegas next month to about 400 family doctors, and hope to be reporting from ASH again in Atlanta next December. But I have much bigger plans, Stay tuned

But first I need to visit my granddaughter.

And for something a big more upbeat than CLL, I am growing my own organic tea. We have two beautiful camellia sinensis, variety sinensis bushes each about two feet high. Tried my first cup. Picked a few leaves that had fallen off or been injured in transit, let them wilt in the shade for a hour, steamed them for a minute, dehydrated them at low heat, and then brewed the crispy leaves at 175 º for exactly 75 seconds. A rich smooth flavor, a lovely golden color, an almost silky taste in my cup. I am in heaven. Why didn't I try this before? I will need to let them get much bigger before I can harvest enough to meet my "habit" and must avoid for now picking the new tender growth that makes the best tea, but it's a good start.

It's always good to be starting something new.

Giving my Veins a Rest. I've seen the Needle and the Damage Done

Ever since my low platelets appeared on the scene six years ago in my CLL battles, there has been very few weeks that I have not been poked or infused in one arm or the other often several times.

Except for the time of my transplant when I was having blood drawn four times a day and might have three or four infusions all hooked up at the same time, I have not a PICC (peripherally inserted central catheter) and I have never had a "port".

Here are my tips that I use for protecting my precious veins.

1: Showing up for any and all blood tests or cancer center appointments well hydrated and warm.
2: Regularly working my arms muscles with weights.
3: Applying pressure quickly and firmly for a few minutes when the the IV is withdrawn.
4: Following that with the compressive dressing COBAN for about another 30 minutes.
5: Most importantly asking for an experienced infusion nurse who gets no more than two tries before letting someone else have a go.

Over the last six years, I have received multiple therapies, at one time three infusions a week, and over the three months in Columbus for the Ibrutinib trial at OSU I got weekly ofatumumab infusions eight times. Add to that too many IVs for the contrast for my CT scans and too many blood draws, and it is a wonder my arms don't make look like those of a heroin addict.

This is another big advantage of the new small molecules- they can pass through the gut undamaged, so they are bioavailable orally. No more IVs. This isn't just more convenient. It is safer. It passes the control of our life saving meds and in some way of our cancer itself from the IV nurse and back to ourselves and our medicine cabinet at home.

My most constant companion over the last six years has not been rituximab or steroids, but the very precious IVIG for my ITP. When my platelet count dropped again the last time, Dr. Kipps recommended that I restart my IVIG but that this time I receive less each dose but get it more frequently, every two weeks, and I dutifully did just that for years. IVs every two weeks! I am now trying to stretch out that two week interval, not that I don't just love spending hours at the friendly infusion center more than twice a month. Not that I don't love having to plan every trip or vacation or appointment around the scheduling of my life saving protein elixir dripping into my veins. I am happy that it has worked so well and that I have access to such a precious and expensive product on a predictable basis. I am truly dependent on the kindness of strangers whose pooled blood product regularly coats my platelets and prevents their premature and dangerous destruction. It is true at so many levels that I am living in gratitude.

Today it was almost four weeks since any needles have pieced my skin, and my platelet counts remained stellar. My Hgb has climbed a bit (13.2), my white blood cells are prefect (8.2, diff pending), and my platelets are 363,000, a very safe and happy number.

And my veins are loving the time off.

Maybe it's a benefit of all the ofatumumab. Makes sense since rituximab helps ITP and they both target CD20+ cells. Maybe it is the ibrutinib reducing my disease burden, the driver of my distorted immune function, or maybe it is some direct effect the BTK blockage has on auto-immune function.

Once a month IVIG. Two more doses of ofatumumab.

A lifetime of cancer controlling pills?

This is a fine vision of my future.

RULE 2 WHAT I HAVE LEARNED My Personal 10 Rules for Staying Alive

A while back I gave my first rule to live by if you have CLL.


Here is my second.


You have time, but you don’t have forever.


CLL is a chronic disease that gives us time to rub our chins, study our enemy, gather our allies, read about what has worked and what has not, check the wind, and plan our attack.


True, there are times when prompt action is called for, such as when I found myself bruised up with single digit platelets from ITP. I was on call for my group when I received an urgent call at home from my exchange that they had a critical lab level on Dr. Koffman. A few hours later I was in hospital getting IVIG and steroids, but that is another story. Moving fast may have saved my life. Similar stories abound for friends with critically low blood counts that needed urgent transfusions and others with serious infections that had to be treated stat. Some secondary tumors such as an aggressive breast cancer demand quick decisions and actions and take precedence over the more pokey CLL.


But these are the exceptions.


Most of the time CLL lets us move carefully, slowly and methodically. We should be prepared, but not usually preemptive and never rash. 


However, there are what Chaya Venkat and others call windows of opportunity that open and also shut.


It is like the stock market. The best time to have bought Apple stock was years ago, not after its big run -up.


Here are three common scenarios that demand we move with alacrity.


The first is financial.


1: 


Sadly pending insurance or job changes can force us to play our hand early. If we are going to be considering treatment in the near future but will have no insurance then, most of us would would not have the deep financial resources necessary to afford therapy. That is reason enough for some of us to move up treatment time.


The next is the most important, the most common and the most ignored.


2:


I tell anyone who will listen that the best time to treat your CLL is a month before you need to. Once our bone marrow is impacted and our counts are too low, many traditional therapies become much more problematic. Once our nodes are huge, many meds can not penetrate as well to get a complete remission and some such as alemtuzumab (Campath) are useless. Once we develop any new problems with our heart or our arteries and veins or our lungs or our kidneys or our even with our psyches, treatment can become much trickier. 


That's why it is important to keep a watch on the cancer. That is why a short lymphocyte doubling time is one of the agreed markers that says time to treat.


Today there may be a new reason to not delay taking action.


3:


Some of the new promising novel therapies such as ibrutinib and GS-1101 have limited openings in their trials, so if we are likely to need therapy soon, and want to have a shot at one of these new experimental agents, we need to watch what's happening with the trials at Clinicaltrials.gov, stay in touch with our support group locally or online and be prepare to move.


Still I would never recommend getting therapy that is not indicated just because an exciting trial is available now and won't be soon.


There is a cost to doing anything. 


There is also a cost to doing nothing.

Savor Mystery

This is all shamelessly stolen from Prevention online.

I usually dismiss it as a terribly researched and sensationalist rag, but this whole article on happiness is quite sweet. I recommend it.

"In a culture obsessed with the power of information, the fact that most of us are a little unnerved by uncertainty is hardly surprising.

Yet research suggests that a dash of mystery can make positive experiences last longer. In one study, University of Virginia psychologist Timothy Wilson, PhD, and colleagues found that students who were given a $1 coin with little explanation reported feeling happier a few minutes later than those who were given either the same amount of money by a known source or no money at all. Wilson argues that those who didn't fully comprehend the reason for the gift spent more time mulling it over, extending their pleasure. "Once we've done the cognitive work to understand something, we kind of wrap it up in a little package and store it away and move on to other things," he explains."

One of the blessing of living with CLL and ITP, clandestine killers that I try to keep locked away in my medicine cabinet, is that you never know for sure what tomorrow will bring.

I got the full article from King Abdulaziz Medical City, Riyadh, Saudi Arabia that I mentioned in the last post and deep in the text I discovered that the 3 patient in the study with ITP who like me also had CLL all responded to rituximab, two with complete responses, and 1 with an enduring response > 1 yr.

Nice surprise when I read the details. I can already feel my brain tying the white bow around that tiny factoid, including the directions for use and looking for the enclosed 20 year get your life back guarantee, as I move forward.

337,000

My platelet count has increased 11 fold since starting the rituxumab (R) and cyclosporin (CSP). I must saying it is working better than I or any of my doctors predicted for my unorthodox therapy. Now if only my pension plan would do the same.

337,000 is more than double what it was last week, and last week it was already normal. This is the highest level since they crashed when my ITP came back last July.

This unusual but not too toxic med mix is unknown territory, so the length of my first course of R or the dosing and timing of R maintenance is stuff that needs to made up as we move forward.

Moreover CSP has a mixed rap sheet. It helped my CLL and there are a few case reports of its anti-leukemic effects, but it is immune suppressive and could and has taken the brakes off cancer growth for others.

Maybe the true hero of my present story is the sesame oil one tablespoon twice a day that the herbalist recommended for low platelets even though the medical literature, while not silent on this, is also not screaming out the proof of its efficacy.

Maybe it's the Beatles watch that I have taken to wearing to bed with me. Everyone knows how good the Beatles are for platelets.

Yes, I am expecting a long and easy course, and a healthy happy pause before I must change course again.

If the family can work it out, maybe I will finally go hang gliding this weekend.

I was in the right place

The Night Tripper

But as the good Dr John said: It must have been the wrong time

My cyclosporin(Cs) level (the immuno-suppressive drug I restarted with rituximab for my low platelets) was 1011 two hours after my AM dose. Normally we want to see the level between 100-300.

This is a very toxic drug, but the rest of my lab, especially the sensitive renal function tests as Cs is a notorious kidney puncher, were all boringly within nomal limits. My blood pressure was up a bit which is another comment adverse event, but still quite safe.

What should I do? Hold a dose which I did while waiting for an answer, and restart at a much lower level? Dr Sharma was not sure. me either, so we turned to Dr Forman who uses this drug for protecting transplanted marrow.

And why no side effects? Not that I was complaining.

Turns out my peak level is meaningless. The trough levels are the whole story. measured at the end of the last dose, generally in the morning BEFORE the first dose that day. When taken by mouth, it is a twice daily med.

Cs with it's more measured modulation of immunity, is THE drug that opened the door to solid organ transplants. Before it burst on the scene, the only player in that arena was the infamous carpet bomber of the immune system, high dose steroids, and outcomes were not good.

The theory is that in order to prevent the beginning of the rejection of a transplanted organ (heart, kidney) it is critical to not let the Cs level dip below a certain safe threshold that is adequate to turn off the natural immune triggered rejection response.

I would guess the same principle applies to shutting down the immune modulated destruction of my platelets, but I don't know that for sure.

It is an off label, though not uncommon, use of this medication to treat ITP, so I bet pounds to peanuts that the guidelines are based on historical consensus and not on well designed studies.

So the peak levels meant nothing to anyone, and I am back on the same dose, waiting to get a trough level next week.

Lessons relearnt:

Timing is everything.

Details matter.

I miss stuff, so ask for help and keep fact checking.

And finally,

Not every result that looks scary, is scary.

PS Dr. John is performing at the Coachhouse next week. Very tempting.

32,000

That was my platelet count today.

No way to sugar coat it. This is bad news. To say otherwise, to borrow for my last post would stink up the place with the powerful and obnoxious odor of mendacity.

Before I go into the details of what I see in my road ahead, I need to thank a few people.

The radiologist at St Jude triple booked my CT scan, the lab staff stayed late to redraw my blood (and give me a proud tour of their new facility), Dr. Sharma acted quickly and decisively to get the ball rolling, Dr. Forman weighted in and seconded the plan expeditiously by email, the nurses were all great getting the paperwork aligned, the scheduling staff at the hospital and at the clinic wrought miracles, and my wife was right there for me.

It will all be fine, just different and busier, but fine. Have no doubts. It will all be fine.

No panic, please. No big changes. I am just turning off the cruise control and driving myself, with a lot of help from my friends. I am still heading to a place of a healthy old age. And I still plan to have a hell of a time getting there. No stinking ITP is going to spoil my fun.

Very latest news and it's good

The preliminary biopsy report shows about 5-10% involvement, with both a nodular and diffuse pattern. The chimerism was basically "host" both in the total and the T cell. This is good news. A miraculous disappearance of all the cancer would have been better, but I'll take this in a heartbeat. The CLL is not gone, but it is not taking off either. It's moving nice and slow, so so can I. Final results on Monday.

Not sure what "basically host" means and what the implications are in terms of using the same donor or finding a new one for a second transplant.

But there is no rush now to figure this out.

Either way, looks like the CLL is not forcing my hand. Except for the ITP, I wouldn't have much to worry about. If the ITP continues to stay controlled with only IVIG and clean living, I am on cruise control. Sweet.

All remains good in the land of platelets

My platelets were in the normal range -157,000- before the first drop of today's IVIG coursed through my veins. That is a drop from 220,000 on Set 18, but that was a full 17 days ago when I last got a dose of immunoglobulin. Today the count is not only still in the normal column on the report, it is way out of the danger zone of <30,000.

In fact, they haven't been out of the normal range since Aug 21, and their nadir was a very very safe 99,000.

The fall had actually started to level out before I started treatment. ITP has been known to hit hard and then peter out.

The CT scan in August had showed possible very small splenules. Sometimes after a splenectomy, small accessory spleens, dormant since birth, get a wake-up call and start growing to do the work of the missing spleen in gobbling up dead and dying red cells and platelets. Sometimes the splenectomy itself spills a few cells in the surgery itself that find a home in some warm vascular bed and start growing up. This is called splenosis. In either case, ITP or AIHA can return.

Neither these processes, by the way, have anything to do with the return of CLL. They can happen in garden variety ITP, with no cancer as the driver.

There are special scans (heat damaged RBC or the old school liver-spleen scan) to look for the suspect tissue, though there is some controversy on which is the best method. Either needs to matched up to the CT.

A glance under the microscope is much easier, cheaper, and radiation free. It may reveal Howell-Jolly bodies, that shouldn't be there if the spleen or splenules are doing the job. I have Howell-jolly bodies.

None of this is 100% predictive.

One option is to do the special scan, see if the suspect areas on the CT light up, and if they do, consider a second and much more minor outpatient laparoscopic accessory splenectomy.

The success rate is quite variable, between a 0-66% success rate. I suspect it depends on the experience of the surgeon along with other factors, such as age. I can find no literature saying that response to first splenectomy is predictive. Or if the presence of Howell-Jolly bodies have any prognostic significance. Size of the splenules is not a factor. Seems 0.5 cm mini-organs can do yeoman's work and when they are removed the chance of a cure is the same as those with bigger born again organs. Response to IVIG does predict good results with primary splenectomy. By the time I had my primary splenectomy 2 and 1/2 years ago, I was no longer responding to IVIG. The operation didn't work. But I sure am responding well now to the infusions every 2 weeks.

That said, while IVIG is a not remitting therapy, it is getting the job done with little muss and fuss and I kind of like the idea of maybe having a mini-spleen protecting me against encapsulated cocci with flu and pneumonia season on the way.

So unless Kanti Rai tells me otherwise, no more video games to be played in my belly for a while. If I have splenules, they can relax for a spell.

I am not sure if my platelet count would be safe even without the IVIG (remember the fall had maybe stopped in the week in August prior to starting treatment), but I am not going to stop it and try to find out. IVIG is after all IMMUNE globulin. It does double duty, protecting me against all things infectious, so I am not taking any chances and am instead counting my dual blessings.

I am doing well, and plan to continue to do so for a long long time.