Rewind...

I had a clinic appointment yesterday and got my FACS and BMBx results:

Peripheral blood flow is unchanged over the past 3 months and holding at .04% hairies.
Aspirate flow is at 4% -- up from 2% last May.
BMBx immunostaining shows 5% infiltration.  That means I'm no longer in remission.

It could be that my aspirate and blood flows always had hairies, but they were just masked by Rituxan until it detached from the cells and flushed out of my system.  Still, the Rituxan treatments had an effect.  Prior to Rituxan, my bone marrow infiltration at 6 months post-chemo was 30%.  Now it's just 5%.  Likewise, my blood counts are now about the best they've been since treatment started and they got a real boost after the Rituxan treatments.

The protocol calls for another round of Rituxan treatments at 6 months post-Rituxan if the peripheral blood flow is positive, so I'll be going in to NIH next Tuesday to get some more aspirate drawn for the PCR lab, then I'll start the first of 8 more Rituxan treatments (1 a week for 8 weeks) in the early afternoon.

The basic gist is this:  given that my hairies' DNA doesn't bind to the baseline PCR primer used for the hyper-sensitive MRD analysis (and any variants they may have tried), my HCL genome is likely mutated from the norm such that they don't die as easily as most, even though they have more than 100,000 CD20 antigens and bind really well with the Rituxan.  The exact nature of the mutation is still not known.

Since I was slow in responding to Cladribine and didn't get a knock-out punch from Rituxan, I wonder if the assumed mutation affects lipid raft function and restricts the biochemical reaction associated with hairy cell apoptosis and antibody-dependent cellular cytotoxicity (ADCC), but there's no way to know that for sure (for now anyway).  Likewise, the high and fairly steady flow in the aspirate leads me to wonder if there is a significant physiological change or maturation of the cells as they move from the aspirate into the marrow and peripheral blood that makes the pb and marrow cells easier to kill (a more normal lipid raft structure)?  Regardless, the prevailing theory is that the hairies in the aspirate are clumped together in a ball and the Rituxan can't peel away enough layers of the onion to eliminate them completely.

In any case, I'm hoping this round will provide more of a wallop since the bone marrow infiltration is less than before.  Still, at 4%, the aspirate flow is the same as when I started Rituxan treatments in November of '09, so it's anyone's guess as to what we'll see a year from now. 

Til then, I'll keep pushing the rock!

Merry Christmas to all and a Happy New Year too!

Restaging

Monday was a busy morning for restaging at NIH:
        1) 17 vials of blood at 7 am
        2) 45 minutes in the MRI hotdog chamber at 8 am (sounded like I was surrounded by a swarm of helicopters)
        3) Ultrasound at 9 am.
        4) Bone Marrow Biopsy at 10 am.
        5) EKG at 11
        6) Back to work at 1

I should get my FACS results for the bone marrow aspirate and peripheral blood in a couple days.  The good news is that ultrasound of my spleen shows that it now measures 10 cm.  That's down from 13.4 cm at diagnosis, and means the overall volume at diagnosis was 2.4 times what it is now -- comparitively large although a spleen size of 13.4 cm isn't abnormal for a tall man.  This bodes well for having delivered a fairly strong punch to the hairies.

The bone marrow biopsy was the most pain-free so far, but mine was still done by hand -- not the new bone marrow drill that gets the job done in just 10 seconds.  NIH started using the drill recently, but they didn't have any bits left from the initial order, so I'll have to wait until next August (biopsy #7)  to see if the drill is as fast and painless as claimed.

My CBC results were very good.  The WBC is back up to 3.74, platelets are up to 139 and ANC is at 2.5.  There is no sign of any fat in my liver and my AST and ALT are still great at 20 and 30, respectively.

We're assuming the FACS will be positive, so I'm scheduled for a clinic appointment next Wednesday and will start my second round of Rituxan on the 28th -- 8 cycles over 8 weeks.  When I'm done this round, I'll have received 16 cycles of Rituxan over the course of 16 months.

I'll post my FACS results as soon as they come in.

Hairy Cell Leukemia: I Want a New Drug ...

I want a new drug... 

Okay, maybe not yet, but it looks like there are lots of new potential candidates for treating HCL that still have yet to be explored.  Two posts ago, I mentioned a new third-generation antibody that has the potential of being 5 to 100 times more powerful than Rituxan but hasn't been used to treat HCL yet.  I'm hoping some preliminary in-vitro studies will be conducted soon.

Today, I found another one -- a Btk (Bruton's tyrosine kinase) Inhibitor, PCI-32765, that is currently in Phase I clinical trials in patients with B cell malignancies (specifically Non-Hodgkin's Lymphoma).  Btk is an essential signalling factor needed for the development of  B-cells.  By inhibiting it, the Btk protein production is blocked and B-cells can't develop.  The inspiration for developing the drug was born from a disease, XLA, in which B-cells are absent from the peripheral blood because Btk is not produced due to a Btk gene defect. 

What's great about this drug is that it's a pill, taken orally, that inhibits Btk production and thus B-cell production.  Since HCL is a B-cell malignancy, I've asked the Hairy Cell Consortium if they are familiar with the drug and whether it may be a candidate for a Phase 1 trial to treat relapsed and refractory HCL patients.  I'll let you know if they respond. 

"This is a very selective compound for B-cells, and it could represent an important alternative to rituximab therapy for the treatment of B-cell NHL. Other obvious applications include autoimmune disorders such as rheumatoid arthritis and lupus, and Pharmacyclics also has strong preclinical efficacy with PCI-32765 in these disease models," said Dr. Mark Genovese, Professor of Medicine and Co-Chief of the Division of Immunology and Rheumatology at Stanford University Medical Center and member of Pharmacyclics' Scientific Advisory Board. [Taken from Pharmacyclics Press Release dated April 13, 2009]


Wouldn't it be great if we HCL'ers could knock out minimal residual disease (MRD) and then take a pill as maintenance therapy so that we'd never have to worry about it ever coming back?  Even better if it could act as the first-line therapy someday and eliminate the need for chemotherapy altogether (and side-effects like increased secondary cancer risk and impact to T-cell counts), or provide  a new treatment alternative for patients with HCL-V (the variant form of HCL that doesn't respond as well to Cladribine).

Prediction?...Pain!

After months of putting it off, I finally went to a new dentist last week.  He told me to see another endodontist to get a second opinion about the root canal and fistula that never resolved after the retreat 18 months ago.  The endodontist told me he's stymied, that it's not good to let the fistula linger because of possible bone damage, and to get the tooth (#14 molar) pulled.  Since the tooth extends into my nasal cavity, they may have to sew in some new bone to make it heal faster.  Once it heals, they'll install a post and a false tooth. 

Oh, and my dentist found a cavity under a cracked filling. 

The tooth extraction and filling cover the first week of December.  The following week, Dr.K is going to restage my progress in case they need to retreat with another round of Rituxan, which means another bone marrow biopsy (#6) on the 13th. 

My good friend Mr. T would like to have a few words:

Prediction? ... Pain!

The protocol has officially been ammended to allow two rounds of Rituxan for the delayed Rituxan cohort (the one that I'm in).  It's a simple one-line addition:  "Also may repeat for those with blood MRD six months after delayed Rituxan."  My flow was negative at 6 months post-Rituxan but has now been positive for 3 months, and will likely still be positive when I restage, so I'll probably receive another 8 rounds of Rituxan starting in January.   I'm very hopeful that this round may be even more effective than last year's since my counts are in good shape and my neutrophil level is much higher.

A high neutrophil count has been shown to correlate with improved antibody-dependent cell-mediated cytotoxicity (ADCC). In other words, the more neutrophils you have when you start Rituxan therapy, the more they can help kill the cells that are tagged with Rituxan. I'll be interested in seeing if I have another incidence of Rituxan-Related Late Onset Neutropenia (RRLON) at week 14 this time around.

I had a physical at my PCP on the 3rd.  Everything checked out fine.  My liver enzymes are holding steady at 22 for both the AST and ALT and my HDL is back up to 40 for the first time in 2 years!  I received 3 vaccinations:  tetanus, pneumonia, and flu.  I couldn't move my left arm for 4 days, but now I feel great.

Aside from that, I've been dabbling in some new favorite hobbies: studying organic chemistry, molecular cell biology, genetics and bioinformatics so that I can better understand some of the papers I've been reading on antibody research and lipid rafts.  I wish I could go back to school full time. 
(12/2/2010)  Tooth Extraction Follow-Up:  Had the tooth pulled.  Everything went fine, and the major bleeding stopped within minutes, although there was a very slow trickle afterward.  I'm hoping this means that there is continued improvement in my platelet count.  I was able to go without any gauze within 3 hours (probably sooner if I hadn't been so cautious).  There were several cysts (about 1 to 1.5 mm) that had formed at each root tip and had to be rigorously scraped off the bone after the roots were extracted.  The worst part was the high pitched squeal of the drill used to segment the root sections so they could be pulled individually.  1 day later, everything feels fine.  I just need to eat soft foods and avoid that side of my mouth for a few days.  In 2 to 3 months, I'll have an exam to verify the bone has grown back and then get a post installed.

A New Hope

Good news!  The latest FACS results from blood taken on September 30th indicate no change in the peripheral blood hairy cell burden or the percentage of lymphocytes that express the hairy cell phenotype (characteristics).  This gives more credence to the hypothesis that the positive FACS results are due to the Rituxan monoclonal antibodies (mAbs) detaching from the residual hairy cells and clearing my system.  The hairy cells may have always been there, but now they are no longer masked by the Rituxan and are once again detectable by FACS.  The important point is that the percentage of hairy cells in the blood remained unchanged at .04%, so the malignancy is not dividing/growing in numbers.  We'll continue to monitor over the months to come, but given that the results are identical to those from 4 weeks ago, I'm very hopeful.

Here's a video of my latest bloodcounts.  Please excuse the melodramatic soundtrack,  I was just indulging in some creative publishing ...
In other news, I'm very excited about a drug I found while researching the relationship between lipid rafts and anti-CD20 monoclonal antibodies.  It may have significant potential in treating HCL -- perhaps 5 to 100 times greater potency than Rituxan.  Pursuant to my inquiries, HCL investigators, who were previously unaware that the drug existed, are now performing detailed analysis of its potential in treating HCL that could lead to some preliminary in vitro laboratory studies.  If all goes well, it may be used in a Phase 1 trial to treat HCL patients who otherwise would have to resort to palliative treatment options.  Maybe several years down the road, it will also become part of the standard arsenal in treating this disease. 

We HCL'ers are fortunate to have so many options and doctors who are willing to listen to and pursue our questions.  It's a good feeling to know that in some small way we can help fight the war on cancer and not be its victims.

Double Trouble

The tumor load in my peripheral bloodstream doubled over the past 3 weeks.  I had a FACS done on August 31st, and the report indicated the percentage of hairy cells increased to .04% from .02%. If the cells are really doubling every three weeks, then I'll have an appreciable burden (around 1%) by January.  Currently, about 5% of my lymphocytes are hairy cells.  I just got the flow results today and haven't talked to Dr. K yet about what it all means.  Still, I've asked to have another flow on Sept. 21st.  If the burden doubles yet again, then I'd like to get another bone marrow biopsy in early October to see if the cells are back in the core.

On the bright side, my counts are continuing to improve, so at least the hairy burden is currently low enough so as not to significantly impair my marrow function.  My WBC is at 4.03, my neutrophils are at 2.6 and my platelets are at 141 -- an all time high since treatment.  I'm still hopeful that I might be able to get another Rituxan treatment while the overall burden and clump sizes are low.

I've read some interesting articles on leukemia using fat as fuel as well as fatty acid involvement in hairy cell membrane morphology.  A study demonstrated how drugs that inhibit fatty acid oxidation may sensitize leukemic cells to drugs that induce apoptosis.   I'm very interested in finding out whether there is a relationship between fatty acid oxidation, body mass index (BMI) and the effectivity of Cladribine.  If one could show that people with lower BMI respond better to Cladribine chemotherapy, then perhaps general approaches to reducing BMI prior to treatment with 2CDA could result in better outcomes for all patients.  My crazy brain at work.  (Afternote:  Turns out there is a basis for my query regarding a correlation between BMI and chemotherapy, although it's not directly related to HCL.  A study of childhood leukemia patients showed that patients with high BMIs were less likely to respond to chemotherapy.  While the theory reported is that cancer cells sequester in body fat, I have my feelings that cellular membrane factors may be involved as well.)

Time to go exercise...

(More random thoughts, 9/9/10) I've been reading about cellular plasma membrane structures called "lipid rafts."  Although these structures are readily observed in cultured cells, they have not been observed in live cells, and their existence in live cells is considered controversial; however, I wonder if hairy cell filopodia (aka villi -- the fine hair-like projections of hairy cells) are actually extrusions of cytoplasmic material from lipid rafts which have large cholesterol concentrations (remember -- hairy cells have high cholesterol content).  I read an abstract from a study entitled "Lipid Raft Disruption Prevents Apoptosis Induced by Cladribine."  It indicates that although leukemic test cells completely absorb Cladribine, disrupting the lipid rafts inhibited the flow of calcium ions through the plasma membrane and reduced the apoptotic effects of Cladribine.  Although the study used ALL cells, I wonder if this is a reason why Cladribine doesn't work well for some HCL patients (the lipid rafts are disrupted or vary in some way that prevents proper biochemical flow to induce apoptosis).  Still, the study probably used cultured cells, so it's hard to know if it applies to live cells.  I'd like to get the full article and learn more about the causes of lipid raft disruption to find out if there are things that can be done to make Cladribine more effective for all patients.  Who knows, maybe this is a factor in HCL-V, and figuring out a way to open the ion pathways will make Cladribine effective in that variant of the disease too.

Similarly, treatment with interferon-alpha has been shown to reduce HCL cholesterol content and villi length.  This would support my theory since lipid rafts are assumed to contain large amounts of cholesterol.  Reducing the cholesterol content of the lipid raft would reduce its area and correspondingly, the amount of material extruded to form the villi would be reduced -- resulting in shorter villi.  I don't know why I write this stuff.  Aside from the fact that I'm desperate to kill these hairy bastards, I suppose I'm hoping a grad student will take it on as a project or at least comment on its plausibility.

(Even more random thoughts, 9/10/2010)  This is kind of cool.  I just found an abstract for a study entitled "Microvilli structures on B lymphocytes: inducible functional domains", which states:  "We also discovered that depletion of cholesterol, using b-methyl-cyclodextrin, lowered the number of microvilli, indicating that intact lipid rafts are required for their expression."  This applies to the microvilli of normal cells, but it is in keeping with my hypothesis regarding unusually large lipid rafts as the source of the filopodia (aka villi of hairy cells.  Perhaps my hypothesis is right.  Now if only I could win the lottery and fund my own studies...

Interestingly enough, there is a patent for a formulation of Cladribine that uses b-cyclodextrin as the soluble agent in lieu of the original benzyl alcohol and propylene glycol cosolvent soluble agent combination.  This is a similar compound as that referred to in the paragraph above (Both β-cyclodextrin and Methyl-β-cyclodextrin (MβCD) remove cholesterol from cultured cells) and it's used to deplete cholesterol and reduce the number of microvilli on B lymphocytes.  If hairy cell villi are indicative of lipid rafts, and lipid rafts are necessary to allow ion flow and induce apoptosis, then perhaps this formulation of Cladribine is slightly less effective than the original version.  I'd like to know which version of the drug I was given.  If b-methyl-cyclodextrin acts as a lipid raft disrupter, then maybe the original formulation is more effective in patients with variant lipid raft function.

(9/11/2010)  I found another great article:  "CD20-mediated apoptosis: signalling through lipid rafts," which seems to imply that in order for Rituxan to induce apoptosis, it must cross-link CD20 proteins that are located in separate lipid rafts.  My initial thought was "does this mean that if your cells have fewer rafts or if the rafts are too large, the drug will be less effective?" and this thought turned out to be mirrored in the final thoughts of the study report: "Finally, it will be important to test the prediction that the size or abundance of lipid rafts in B-cell membranes is a contributing factor to the susceptibility or resistance of patients to CD20-mediated B-cell depletion."  This study's findings resonate a common theme with the other studies I've referenced regarding the involvement of lipid rafts in apoptosis.

Much of this report seems to read as if the high cholesterol content of the cells is necessary in order to allow the calcium ion flow needed for apoptosis to work properly.  This would indicate that going on a low-cholesterol diet during therapy to try to starve the hairies may be counter-productive.  Since the underlying apoptotic biochemical process seems to be the same for Cladribine induced apoptosis as it is for anti-CD20 induced apoptosis, maybe cholesterol gets synthesized into other chemicals during apoptosis -- causing the hairies to suck in more cholesterol from the peripheral blood as they try to survive.  Maybe this explains why my blood cholesterol dropped precipitously during Cladribine chemotherapy (HDL went from 30 to 18 in a matter of days, LDL went from 90s to  high 60s).  I'm guessing that partial apoptosis biochemical processes started and consumed cholesterol, but the calcium mobilization was inhibited so as the cells survived, they consumed more cholesterol from my peripheral blood to reconstitute themselves.  Ultimately, many of them died after six months (went from 80% bone marrow infiltration at 1 month post chemo to 30% at 6 months) probably due to DNA damage and slow but sure calcium mobilization, but too many survived.

I found another article which reinforces and provides further detail on the involvement of cholesterol in B-cell apoptosis: "Cholesterol depletion inhibits src family kinase-dependent calcium mobilization and apoptosis induced by Rituximab crosslinking."

Hmmm....does this mean I should eat Ben and Jerry's Vanilla ice cream during therapy?  Of course not, fat and cholesterol are different substances.  Maybe shrimp is a good compromise -- low in fat, but high in cholesterol.  Leukemia is so paradoxical to the conventional mindset.  This is interesting because studies in many solid tumors (like prostate cancer) show that cholesterol depletion aids in apoptosis.  The differences between leukemia and solid tumors are fascinating.  Time to go watch Woody Allen's "Sleeper" -- turns out chocolate cake is good for you after all...

(9/18/2010)  I got a great reply from the "Hairy Cell Consortium" regarding some questions I had regarding lipid raft research for HCL:

My e-mail to them read as follows:
      Given the findings of the following studies:
          "CD20-mediated apoptosis: signalling through lipid rafts"
          http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782791/pdf/imm0107-0176.pdf

          and

         "Lipid raft disruption prevents apoptosis induced by Cladribine"
          http://www.ncbi.nlm.nih.gov/pubmed/16730061

          isn't it possible that lipid raft disruption may play a
          significant role in why these drugs
          are are not effective for some patients?
          Why isn't there more research to characterize
          HCL lipid rafts and determine the role that lipid
          rafts have in the disease?

Here's their reply:
 
         Dear Mr. Howard:

        
         The question that you pose about the potential
         importance of "lipid rafts" and response to therapy
         in hairy cell leukemia is excellent. To our knowledge,
         the characterization of "lipid rafts" in hairy cell
         leukemia has not been published. In contrast, lipid
         rafts have been explored in chronic lymphocytic leukemia
         by several investigators. The presence of lipid rafts has
         been correlated with response to cladribine as well
         as response to monoclonal antibodies in vitro. The
         monoclonal antibodies that have been studied include
         both Rituximab and Alemtuzumab. Since both of these
         agents may have some benefit in this disease, all patients
         have not responded. It would be interesting to
         correlate the responsiveness to these agents as well
         as to the purine nucleoside analogues. This is the type
         of study that might be conducted within the Hairy Cell
         Leukemia Consortium. Your question has merit
         because it might provide predictive biomarkers to
         determine who will and will not respond to these agents.

       Regards,
       The HCL Consortium Team

This response made me very happy.  Hopefully, they'll perform some studies.  Who knows, maybe the research will not only provide predictive biomarkers but ways to tailor the structure of antibodies to conform to variances in lipid raft size and placement that fall outside the range accomodated by the current antibodies' structures.

The FACS of Life

You knew it was only a matter of time before I had to use that corny title for a blogpost, but bear with me, it follows a coherent theme.

Other candidate titles for this post included:
      Dirty Hairy
      From Hairy to Eternity
      The Good, The Bad, and The Hairy
      Gone Today, Hairy Tomorrow
      The Cells that Wouldn't Die
      Protocol
      and Hair We Go Again

Simply put: you take the good, you take the bad, you take 'em both and there you have the FACS of life...

The Good:  The Rituxan treatments worked really well and as I wrote in my last post, the hairy cell burden in my May bone marrow biopsy was zero (although the bone marrow aspirate [liquid] showed 2.1% hairies).  Likewise, I just had a complete blood count last week and my counts are at historical highs since diagnosis, so my marrow is continuing to rebound and keep me healthy.

The Bad:  My FACS results from last week showed some hairies in the peripheral bloodstream (.02% of the peripheral blood monoclonal cells), but there are several reasons for why that may be.

The Theories:
     #1: It's very possible that the few hairies which were bound with Rituxan but not completely killed via apoptosis or immune system attack, were undetectable in prior FACS tests due to the effects of the Rituxan covering the surface.  Now that the Rituxan is flushing out of my system and coming unbound from the hairies, those cells are once again detectable.
     #2:  The cancer that wasn't killed by the Rituxan (some of the cells in the aspirate) are starting to proliferate again and seep into my peripheral bloodstream.

The analysis:
     Usually the simple answer is the correct one (unfortunately #2 is the simplest), but we are sailing in uncharted territory right now, and there is plenty of time to perform more tests over the coming months and really get a feel for what is going on.  Theory #1 is highly optimistic but still plausible, and it's still very possible that as my marrow rebuilds, my immune system will either keep the remaining HCL in-check or attack and destroy it.  Time will tell.

What's next:
     Given how well Rituxan worked the first time considering my HCL burden after Cladribine chemotherapy was still substantial, I believe I would benefit from a second round of Rituxan treatments if they are offered to me.  The possibility of adapting the protocol accordingly for my cohort is being considered (the simultaneous chemo/Rituxan cohort is allowed two rounds of Rituxan, but my delayed Rituxan cohort is currently allowed only one).
    In the meantime, I'm interested in seeing how my body will respond to the remaining hairies and feel that doing some more FACS tests to see if the burden increases or becomes undetectable again will help to substantiate or disprove theory #1.  Over the next few months, we'll run some more FACS tests and see what happens.  Let's hope my immune system kicks it.

Here's a slide show of my latest blood count results:

Since my last post in May, I've really been enjoying life.  Taking lots of time to be with the family, a trip up to Hershey Park, and enjoying the weekends when the heat or rain doesn't make that impossible.  It's been an incredibly happy time and given that the blood counts are continuing to improve, I really don't care about the few cells that were found in the peripheral bloodstream.

I should have another FACS in 4 to 6 weeks.  I'll let you know how it goes.

Moving the Rock.

The rock has moved!

I received my bone marrow biopsy results yesterday.  They read as follows: "No morphologic or immunohistologic evidence of residual hairy cell leukemia."  In other words, negative for hairy cell.  You may recall that the bone marrow infiltration in late October was still 30% six months after Cladribine chemotherapy treatment, just before receiving Rituxan.  The NIH Clinical Trial for new patients combining Cladribine and Rituxan has done a great job!  Excellent news to end one of the most awesome weeks of my life.

The only thing that can put a bigger smile on my face is this:

My daughters

My peripheral blood FACS was also negative for HCL.  The FACS for the  bone marrow aspirate is still positive for HCL (dropped from 4% in late October to 2.1% last week), but the CD20 absolute binding tests show a dramatic decrease in the binding capacity (dropped from a capacity of 80,000 molecules of Rituxan to 8000) because a large amount of Rituxan is now already bound to the existing CD20 proteins on the cells now that I've received Rituxan treatments.  This means it may still be working.  CD20 proteins are overexpressed on the outside of the hairy cells, and Rituxan binds to those proteins then kills the hairy cells.  A significant amount of the cells may continue to die over the next six months, and there is a possibility that the bone marrow aspirate will also test negative six months from now.

I am now in complete remission !!!

New Arrival!!!

I'm proud to announce the arrival of our second child.
She arrived today, 5/13/2010

Weight:  9 lbs, 8.3 oz.
Height:  21"
Ingredients: lots and lots of sugar, spice and everything nice.

Baby, Mommy, Daddy and her big sister are all happy and healthy!!!

Our new baby girl!

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.

.

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!