Benefits of NIH Hairy Cell Leukemia Trial Participation

I've read a lot of bulletin board posts with various insights regarding participation in the NIH Trial for Newly Diagnosed HCL Patients so since I'm participating in the trial, I thought I'd offer my own.

While I have the advantage of living close to NIH, I've been in touch with many patients who have had to deal with the logistics of participating in the trial from all over the country.  Here are many of the trades people make when considering trial participation:

Trade #1:  Can I afford to travel to or stay at NIH for 8 weeks of Rituxan treatments?
         Fact: You don't have to.  Rituxan can be administered by your local doctor.  You only need to travel/stay at NIH for the first week of chemotherapy treatment.  NIH will send the Rituxan to your local doctor and coordinate the administration free of charge.

Trade #2:  My local oncologist can provide the Cladribine and Rituxan combination, so there's no need to participate in the trial.
         Fact: While local administration of the Cladribine/Rituxan combination is becoming more common,  most insurance will only cover the cost of 4 weeks of Rituxan.  By participating in the NIH trial, you'll receive up to 16 weeks (2 cycles at least 6 months apart with 8 weekly rounds per cycle) of Rituxan free of charge.  Most insurance companies view the free NIH-provided Rituxan and expected increase in remission as a major cost-savings and will cover the entire cost of local Rituxan administration (local Dr. time and facilities costs).  Since Rituxan effectivity is dependent on the size/radius of the remaining clumps of hairies, long-lasting remission and eradication is much more likely with 8 cycles per treatment than with 4.  Independent adminstration of Rituxan without monitoring minimal residual disease (MRD) in a clinical trial setting does not provide an effective means of treating the disease.  Once the trial is completed,  local oncologists will be provided with the most effective combination therapy treatment.
      
Trade #3:  The trial doesn't provide any major advantage.
          Fact:  Prior trials in Italy combining Rituxan and Cladribine resulted in a significant increase in complete remissions and elimination of minimal residual disease (MRD).  It is believed that this may increase the duration of remission, which is being studied by the NIH trial.  The NIH hyper-sensitive MRD test is able to detect 1 hairy in 1 million mononuclear cells -- 100 times more sensitive than a standard FACS.  This is a significant advantage -- allowing Rituxan to be administered at a point when it will be most effective.  This also means that Rituxan will only be administered if it is necessary.  Only NIH can perform this test!
                    Whereas most doctors aren't proactive in following their patients and wait until blood counts   indicate the need for re-treatment, Dr. Kreitman will actively study your progress and treat the earliest signs of MRD, which may possibly increase the duration of your remission (one of the hypothetical effects being studied).

Trade #4:  There are risks associated with Rituxan.  Cladribine is highly effective in most patients, so I'll do that for now and only take Rituxan later if it becomes necessary.
          Fact:  Data indicate that 40% of patients relapse after only 10 years of single-drug chemotherapy.  To prevent significant bone marrow suppression, it's desired to limit a patient to two treatments of purine analogue chemotherapy (Cladribine or Pentostatin).  The prevailing theory is that Rituxan is most effective when used in conjunction with a purine analogue so that the clumps of hairies are unclumped/diffused prior to administering it (being studied by the trial).  This allows Rituxan to destroy the individual hairy cells immediately instead of slowly peeling the outer layers of the hairy clumps (resulting in a direct additive effect vs. a percentage of the remaining load).  Don't lose this advantage by deferring Rituxan treatments until after chemotherapy is no longer viable.  One look at my ANC plots (see prior posts), and you can see I owe my overall strong response to the Cladribine/Rituxan combination.

Trade #5:  I can't afford to travel to NIH.
        Fact:  A lot first-time patients deal with the cost/benefit trade-off of travel to NIH, and rightly so.  Once accepted into the trial, NIH will cover the costs of all subsequent travel for the patient (spouses and children are not covered).  Angel Flight and the Air Charity Network offer flights to patients in financial need.

Trade #6: I can't afford accommodations while at NIH.
       Once admitted to the trial, NIH will provide free accommodations through their in-patient hospital.  While qualifying for the trial, you may need to spend two nights at a local hotel.   Current rates for the Bethesda Marriott are approximately $139/night.  You'll find that the current commercial rates are often better than the NIH negotiated rates, so ask for both.

The best way to make a fully informed decision is to gather as much information as possible.  Dr. Kreitman is always available and will quickly respond to your questions.  Email him at kreitmar@mail.nih.gov.

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Turbulence

The approach for my soft landing has been suddenly interrupted by some unexpected turbulence. I had a CBC and FACS performed on Monday. For the most part, my counts were good, but as shown in the plot below, the one exception was a doozy -- my absolute neutrophil count dropped dramatically from 1.97 two weeks ago to .81 on Monday. This sudden drop definitely had me concerned, but to my relief the other counts are still good -- the lymphocyte level remained steady, my platelets increased slightly and my liver enzyme levels are now well within the normal range.

My FACS results came in on Thursday and were still negative -- no detectable hairies in the peripheral bloodstream.  Everything else is good, but the neutrophils have dropped suddenly about 14 weeks after my last Rituxan treatment (12/28/09).  What's going on?  The initial direction from Dr. K is to wait until my marrow biopsy on May 10th to evaluate the marrow function, but after some more investigation, my best guess is that I've experienced a side-effect of Rituxan known as Rituxan related late onset  neutropenia (RRLON). 

A cursory evaluation of the available research papers on RRLON indicates that in a lymphoma study in which patients were treated with both chemo and Rituxan, 23 of 107 patients experienced some form of RRLON.  The typical median ANC nadir point was .61, and required 4 weeks to recover.  I've asked Dr. K for his opinion and a response is pending.  In my opinion, another CBC by next Wednesday would make sense to quantify the nadir and determine whether I'm still on the downturn or moving toward recovery.

I'll keep you posted.
BTW:  here's an interesting article regarding the health care debate ;)

Update:
Just had another CBC today (4/29) per my request, and the news is good!  The late-onset neutropenia (LON) has resolved and all my counts are in great shape (except the platelets).  I'm very confident that this was a Rituxan-related event and pleased that my neutrophil level is now well within the normal range.  As you can see in the ANC plot below, the neutrophil level is almost close to the peak level since I've started collecting CBC data.  Even better, my WBC is the highest it's been in years considering that prior to treatment a large percentage of the WBC consisted of hairy cells.  I'm very happy!!!

Soft Landing

I just had another complete blood count (CBC) on Monday and things look like they're stabilizing. The platelets are still low but within a normal range for remission and since they're stable, I'm happy. I was hoping the neutrophils would increase, but they're still in a normal range although they went down slightly over the past month. As you can see in the plots below, my counts have pretty much come in for a soft landing, and stability in the normal range is a good thing.

Following up on the liver enzymes: they're slightly back up over the normal limits, so I don't think the chamomile tea was a major contributor. I ate some foods with wheat and walnut ingredients a few days before the test (birthday and wedding celebrations), so that may have something to do with it. A fatty liver can cause gluten intolerance and low platelets due to decreased production of thrombopoietin, so I may still be fighting some fatty liver issues.

The weather last weekend was great! I got out and rode my bike 22 miles on the C&O Canal on Sunday. I'm anxious to push for 40 next weekend!

A Hairy Update

The past two months have been great! The February snowpocalypse gave me an opportunity to test my stamina shoveling and snowblowing, and I felt great afterward. I even shoveled out my neighbor's driveway. My FACS tests continue to show 0% hairy cells in the peripheral blood stream, and I'm still waiting for my next bone marrow biopsy in April to see if all evidence of hairies in the marrow has disappeared. I think it has. The Rituxan after the chemo really did the trick.

I continue to limit gluten in my diet and have stopped drinking herbal tea (specifically chamomile). Correspondingly, my liver enzyme levels returned to normal on my last blood test in February. I'm very interested in seeing if they continue to stay down when I go back in on the 22nd, now that I've stopped the tea. Interestingly, my platelets and neutrophils also came down a bit after stopping the chamomile, which is anecdotally tied to increasing neutrophils, but all my counts are still in the normal range.

I'm anxious to start riding my bike along the C&O canal again. Yesterday, I rode 20 miles in an hour using the "Pike's peak" profile at the maximum resistance level on my exercise bike. I would never have been able to do that level of resistance at any time before in my life. I really think I had HCL (and some other issues) "in-check" and undiagnosed for a long time before being diagnosed. I'm anxious to get outside and see what I can do now that it's warming up.

Life is definitely more normal now, although I'm not sure that's necessarily good. I spend a lot less time researching HCL. Still, I try to keep up with the latest news. For those who are interested, here's a link to a hairy cell video lecture by Dr. Kreitman, "Updates on Therapies for Hairy Cell Leukemia", on the current state-of-the-art of HCL research.



We had a 4D sonogram of baby girl #2 on the 7th (Cladribine did not reduce my fertility and may have improved it by eliminating the effects of chronic leukemia).  She was very shy and wanted to bury her head from view but we got several good peeks, and she looks a lot like her big sister. We're very excited to meet her in person in May.

Next Friday, the 19th, is my birthday and coincidentally the day my sister Elena is getting married. It'll be a great celebration with the family, and Claire is excited to be a flower girl with her cousin Olive. The next day, Saturday the 20th, marks 1 year since my diagnosis. I'm grateful to be celebrating it.

My latest labs look good. I'm going back in on the 22nd for another set, so I'll probably update the charts and publish them here when I get that data.

It is a Happy New Year!

My 8th and final Rituxan treatment was last Monday, December 28th, and it feels great to be done. I'm in great shape now, and the Holidays were wonderful. I got to spend lots of time with Claire, who never ceases to amaze me. She'll be 2 this Saturday, speaks in full sentences and loves to keep us entertained by saying such phrases as "Hey, can I have more French Fries please, lady?" to the waitress at Outback Steakhouse, calling us with the redial button from Grandmas without permission, putting her bib on and walking into the kitchen to say "Grandma, I'm hungry", and saying things like "I don't have time to talk right now" and "I love you too, truly" when she pretends to call people on the phone. We also found out that baby #2 is going to be a girl. We're favoring naming her Grace (more like Amazing Grace). If she's anything like Claire, we're going to have our hands full in 4 months...

So far 2010 has been a good year, but I guess 4 days isn't much to go by. Still, the results of my last blood test were great, and that makes me optimistic. I don't look back on 2009 with disdain,I met too many awesome and wonderful people -- patients, doctors, and nurses, and I re-established bonds with friends and family. Isn't Facebook awesome? (ha ha). Likewise, I learned a lot, grew alot and lived a lot. I'm grateful to be doing so well at this point, and thankful for all the prayers and thoughts caring people like you have sent me.

Now, back to the blood. All the reds are back in the normal range (not just by remission standards -- we're talking normal normal). Likewise, my white count is strong and the neutrophils are awesome -- well into the normal range. Most of the remaining lymphocytes are T-cells and NK cells at this point, the B-cells having been wiped out for the most part. I'm hoping the latest FACS (from the post-treatment sample drawn today) will detail those levels, but it won't be ready until next week.

Here are my latest plots. Check out the massive increase in the neutrophils over the past two weeks. The Rituxan really went to town and helped me turn a marginal response to Cladribine into a complete, and what I believe will be a lasting, remission!









Happy New Year!

Wipe Out!

The Rituxan treatments have been an overwhelming success!

While I haven't taken the time to write a worthwhile update on my current status, I'd like to share with you the flow results from blood taken prior to the Week 5 treament. The flow was negative -- no hairy cells could be detected using the standard FACS, which is sensitive enough to detect 1 hairy in 10,000 mononuclear cells.

The Cladribine/Rituxan one-two punch worked and was the perfect combination of what I needed. I'm very relieved and very grateful to have found Dr. K's trial. I've now completed 7 of the 8 weekly Rituxan treatments. The last treatment went very well and didn't require Tylenol or Benadryl pre-meds (to eliminate undue strain on my liver).

A week prior, the treating nurse gave me my Tylenol pre-meds half an hour before drawing my blood for the chem20 tests, which include my liver enzyme levels. Not surprisingly, both the AST and ALT enzyme levels were about as high as I'd seen in awhile. This week, the AST was back to normal and the ALT was 50% higher than normal, which isn't too bad for me. I had a consult with a hepatologist, who wasn't surprised that in general my enzymes were elevated. It is not uncommon in half of all cancer patients, given the stress of chemotherapy and all the other agents the body is exposed to. I don't know if that generalization applies to Cladribine chemotherapy specifically, but it helped me feel better about my roller coaster enzyme levels.

Based on prior imaging tests, it appears that my liver is somewhat fatty, and the hepatologist seems confident that a better diet and more exercise will likely return the liver to normal. I'll continue to persist at maintaining dietary and physical discipline in hopes that the fatty condition of the liver can be reversed. They are running additional tests, but right now, it looks like I'm just paying the price for prior years' poor diet and some genetic pre-dispositions.

Git 'r Dun

Really good news this week!

My neutrophils jumped from 1.29 last week all the way up to 1.70, and my liver enzymes dropped by more than 10%. The AST level is back to normal. Everything seems to be moving in the right direction, so I think I'll stick with the vitamin and chamomille cocktail I described in my previous post. I'm still doing the coffee/caffeine thing too.

As I write this post, I'm getting my 5th infusion of Rituxan. Prior to treatment, they drew blood for a FACS analysis to count the peripheral hairies, but I'm very confident they won't find any this time.

I'll add plots of the last 3 weeks' blood counts tonight, when I can get to a computer.

Here they are. As you can see most of the counts are back up to the levels they were at just prior to my first Rituxan treatment, when they had already peaked and had started to trend downward. Let's hope the upward momentum keeps going.