Hairy Cell Leukemia: Mission Accomplished!

I was going to call this post "A Little Bit of Everything", but fortunately my plans have changed! 

I did it!, or should I say "Dr. Kreitman and The NIH Trial to Treat First Time HCL Patients did it!"  All of my tests are now negative:  peripheral blood flow (looks for hairies in your veins), bone marrow and most importantly bone marrow aspirate (the liquid in your bones where cells develop) are all negative!  I couldn't have done it without the NIH trial.  If you recall, it's taken me a little over two years to get here. 

The initial treatment with Cladribine only led to a partial remission, and I still had 30% bone marrow infiltration and positive blood flows at 6-months post-chemo (November 2009).  At that point, I had my first Rituxan treatment (8 rounds over 8 weeks).  I achieved a complete remission (CR) 6 months later, in May 2010, but still had hairy cells in my bone marrow aspirate (a value not included in determining CR).  That 1st CR was short lived.  The cells in my aspirate continued to proliferate and upon restaging in December 2010, my bone marrow infiltration was back up to 5% and the peripheral blood flow showed .04% hairies.  Although my complete blood counts (CBCs) were at remission levels, the marrow infiltration indicated it was no longer a CR and positive flow results for hairy cell indicated minimal residual disease (MRD), so I was retreated with Rituxan for the second and final time in accordance with the trial's protocol.  This latest treatment wiped out the hairies in all areas to undetectable levels.  I'm not completely out of the woods.  Time will tell if this is a durable remission, but one thing's for sure:  The combination of Cladribine and Rituxan did what Cladribine alone could not without waiting for relapse or subjecting me to multiple rounds of chemo.

Although I've wiped out the hairies, I have one more minor hurdle to jump.  As I discovered and wrote last year, there is a documented phenomenon that occurred in 20% of lymphoma patients, who received combined chemo and Rituxan therapy, known as Rituxan-related late onset neutropenia (LON).  The nadir (low point in counts) typically occurs 14 weeks after the last dose of Rituxan when the counts dip to about 660 (average).  The effect lasts for about 4 weeks.  I noticed a similar effect happened to me after my first Rituxan treatment and blogged about it then.  You'll also recall that I've been interested in seeing if it would happen again.  Well, it happened again!  My 6-month CBC (16 weeks after my last Rituxan dose or 24 weeks after I started this cycle) indicates that my neutrophils are at 750.  Although it appears to be slightly later by 2 weeks, I don't get CBCs often enough to say whether the low-point occured at 14 weeks or not. 

Still, it is statistically in keeping with the findings of the lymphoma study.  I believe I've discovered and am the first documented case of this occuring in an HCL patient.  Time will tell as my recovery and other patients are studied.  I expect to be at a remission level in 3 weeks, when I have my next CBC.  So technically, I'm not in a CR until the neuts jump back up, but I don't really care.  Everything else is in great shape.  Based on my first experience and knowledge of RTX LON, I consider it a nuance that will quickly recover; however, I won't be surprised if the duration of this neutropenia is slightly longer than the first time.

So far it's been a great summer.  My youngest daughter, who was born a year after I was first treated, started walking on her first birthday and can now say the letters in her name.  My 3-year old is doing great and having lots of fun with her garden and playing in the sand and taking swim lessons.  We recently headed up to Lancaster, PA to visit Dutch Wonderland and the Thomas the Train event at Strasburg railroad in our new Swagger Wagon (a Honda Odyssey). 

The sun and I have also come to terms.  I'm going to wear sunscreen and s/he's going to lay off me for awhile.  Likewise, I've set up a portable 60 Watt solar panel array to charge all my mobile devices and run my low power electronics to pay her/him hommage.  Yes, I'm a gadget geek, but if the power ever goes out, I'll still have my iTunes!  I also just bought a kayak and will be taking lots of late afternoon trips on the Potomac this summer.

Yippeekayay !!!

All Hail Ra

I know it's been too long since my last post!

I've got lots to discuss and I'm short on time right now, but I wanted to share an interesting "Science Daily" article that I just found.

http://www.sciencedaily.com/releases/2011/06/110608195159.htm

It states:

The researchers demonstrated that B-cells are deficient in one of the main DNA repair pathways, known as Nucleotide Excision Repair. This pathway repairs a lot of different DNA lesions, including UV-induced damage and chemical adducts (e.g. from air pollution and cigarette smoke). Their model therefore explains why strong UV exposure (e.g. unprotected sun bathing) is the number one environmental risk factor for lymphoma and also supports the evidence that exposure to air pollution and smoking are also risk factors.

Dr Nouspikel said: "Lymphoma is one of the ten most frequent cancers in adults in the UK, and the third among children. If we want to come up with efficient strategies for prevention and therapy, it is crucial to understand what causes it. The novel mechanism we have discovered potentially accounts for the development of many different types of lymphoma. It may also explain why strong exposure to sunlight is the main environmental risk factor for this cancer."

This supports my theory than sunlight may cause mutations (specifically cytosine deamination to uracil in RNA) that cause HCL!  Likewise, it reinforces my hypothesis that the reason they can't sequence my hairy cell DNA is because there is a mutation in my DNA corresponding to the primer they're using which the DNA repair enzymes either failed or don't attempt to repair.
I've got lots more to talk about, like mcl-1 inhibitors and new data at 15 weeks after my last Rituxan treatment that supports my Rituxan-related late onset neutropenia (LON) hypothesis, but it'll have to wait until I have more time.  I'm still waiting to get my latest flow results.

There was a huge Coronal Mass Ejection (CME) 2 days ago that spanned half the surface of the sun and is headed our way, so wear sunscreen!

Later.
6/11/2011 update

Wow!  Just one day later, one of my fellow HCL'ers (shout out to Vincent) found this announcement:

http://www.medpagetoday.com/HematologyOncology/Leukemia/27009

It states that HCL has been narrowed down to a single common gene mutation, BRAF V600E.  BRAF is a gene most widely known for its involvement in melanoma.  This is groundbreaking, and since the leading cause of BRAF V600 mutation is excessive sun exposure, gives further credence to my hypothesis that sun exposure is a leading cause of HCL.  All these studies are starting to add up and reinforce that hypothesis.  It also means that clinical trials with BRAF V600E inhibitors like PLX-4720, which are highly active in treating melanoma, are warranted in patients with refractory and relapsed HCL.  Perhaps a PLX4720-assisted Cladribine / GA-101 trial in refractory and relapsed HCL'ers is in the future...

Here's the published study.

These findings may lead to the development of mouse models for HCL research: 

"On the basis of our findings, it should be feasible to develop murine models of HCL by activating the RAS–RAF–MAPK signaling pathway in specific B-cell subpopulation."

"Strikingly, a T→A transversion occurring at position 1860 of the messenger RNA RefSeq NM_004333.4 and resulting in the V600E variant was found in samples from all 47 patients with HCL..."

I'm hypothesizing that the transversion is sunlight induced.  It will be interesting to see if research related to the first study I cited can determine whether DNA excision repair related to BRAF V600 is inactive during certain stages of B-cell maturation (specifically en route or at the germinal center stage).

It's all coming together.  Needless to say Eddie Vedder's "Hard Sun" is going to be the backup soundtrack for my next bloodcount video...

I Got Chills...They're Multiplyin' ...

You've got to be kidding me!!! Two flus in 1 month ???!!!!

I couldn't believe it.  The baby came down with flu A on February 28th.  I started developing symptoms 2 days later and went to see my PCP.  The quick flu test was negative, and it's supposed to be accurate to 90+%, so he told me it was probably a bacterial infection.  Still, they did a culture to be on the safe side.  I started back on Tamiflu just to make sure I wouldn't get the flu again since the baby had it.  That night, I sweated profusely, just like with flu B two weeks prior.  I was skeptical that I didn't have the flu, and I continued to feel pretty lousy the rest of the week -- fevers up to 102, etc.

That Saturday, my PCP sent me a message saying it WAS flu A, so I increased the Tamiflu dose to 2 pills a day.  It seemed to do little good, and I took over a week to recover.  I later read that flu A can mutate to isolates that don't respond to Tamiflu (it says so on the info packet), so I assume that's what happened.  My recovery from flu B was much faster and had far less Tamiflu-related nausea.

I just had my 3 month Rituxan follow up on March 28th.  The blood counts are looking great!  The WBC is almost back to normal for a normal person, and that's pretty good considering how low my lymphocyte count still is.  Since the hairy cells are B-lymphocytes, you want that count (aka "ALC") to be low.  My neutrophils are holding steady, and my monocytes are really doing well.  I'm sure that getting the flu twice in 1 month didn't hurt getting the monocyte count up, but they're still high 1 month later, so I'm not complaining.  Hopefully, that will assist the ADCC mediated by Rituxan and kill more hairies.

I've lost a lot of time at work dealing with the two flus and taking care of the baby.  She's had chronic ear infections for several months in addition to the flu.  She's finally going to get ear tubes on Monday.  It worked wonders for her big sister, so we're looking forward to it.

Here's the latest video of my blood counts.  Overall, I'm really happy with the results, but my phosphorus level has dipped below normal several times since RTX#2.  I'm not sure if that has to do with marrow replenishment or over-excretion in the urine due to a vitamin D deficiency.  Time will tell, but if it continues to trend downward, I may consult a endocrinologist and try to find out what's causing it.



In other news, it looks like things may be moving forward with a Rituxan vs. GA-101 trial for Hairy Cell in refractory and relapsed patients!  GA-101 is the Type II anti-CD20 antibody I found in September, while studying "lipid rafts", and brought to Dr. K's attention.  It's engineered to have a wider elbow angle which is able to mediate cell death 5 to 100 times more effectively than Rituxan. It's also less toxic.  I'll let you know as I find out more.

Here's a table of drugs for which I'd like to see more data regarding effectiveness in treating HCL:

Rituxan, Flu and a Spike in Counts too ...

I've been holding off this post until I had enough new data to share to make it worthwhile, but  I didn't realize I'd get the flu while I was waiting.  Between treatments 6 and 7, I got hit hard with influenza B.  No doubt my youngest brought it home from daycare.  The youngest had a mild fever two days before I came down with it.  Fortunately, everyone (including myself) had been vaccinated earlier in the season, but since I've anihilated my B-cells, there wasn't much benefit left from the vaccine.  I started feeling aches on that Saturday, but it didn't hit hard until Superbowl Sunday.  I got in bed around 10 am, couldn't really move and stopped drinking enough fluids.  Once my fever spiked to 102 around 3 pm, I called the NIH day hospital, and they asked me to come in.

I got to Bethesda around 4:30 pm.  My fever went up and down between 98 and 103 several times while there.  They ran CBC, chemistry and cultures and hooked me up to an IV.  4 hours, 3 bags of saline and a digital X-ray later, I was good to go with Tamiflu and Tylenol in hand.  The next morning at 6 am, I started sweating profusely on my upper body.  At 7 am, I was awake enough to take off my T-shirt, which I could have rung out to get a couple cups of water in a bucket.  I continued to have roller coaster fevers for the remainder of the day, but my temperature finally recovered later that evening, and I was able to go back to NIH the next day (Tuesday) to receive treatment #7.

Needless to say, my counts spiked as shown above. On the plus side, I had a normal WBC for the first time since collecting counts.  Same with the platelets.  I'm hoping the short term boost may have benefited my ADCC response to the Rituxan treatments too. It can't hurt to have all those extra neutrophils and monocytes available to recognize and target the hairy cells...

Lots of HCL patients have anecdotally commented that when they got viral infections, their counts improved for awhile; however, my response was short-lived and only lasted as long as the viral infection.  One exception -- my platelets seem to have gotten a significant and more durable boost, and are at the best level I've ever measured. Hopefully, that's a sign of good things to come.

I've got lots more to add to this post, including another potential treatment that uses a protein known as CD-19L, found on T cells, to kill leukemia cells that express CD19.  Scientists have now bioengineered CD19-L in a solution without T-cells and shown it to kill ALL cells in vitro.  Since hairy cells express CD19 too, I'm hoping CD19-L will bind to and destroy them.  Hopefully, this bioengineered protein will continue to be developed and result in treatments for ALL and possibly HCL too.

I've been studying somatic hypermutation (SHM) associated with the variable heavy-chain region of B-cell immunoglobulins and wondering if the random production of Ig antibody is somehow associated with HCL mutations.  This has led me to postulate some new theories on the cause of HCL.  I think HCL may be caused by RNA cytosine nucleoside exposure to sunlight that results in deamination of cytosine to uracil.  Next thing you know, the alteration causes a protein to fold improperly, chromosomes mix with the wrong crowd, locks get picked with mutated keys and genes start translocating all over the place.  Before you know it, you've got just the right random blend of mishaps and a self-sustaining HCL mutation on your hands.

Dr. John Sutherland, a Professor of Organic Chemistry at the University of Manchester, England has recently shown that RNA may be the starting point for life and that sunlight alone can deaminate cytosine in RNA to uracil.  This was discussed on a recent episode of NOVA Science Now.  I wonder if sunburn inflammation and UVA/UVB exposure as some B-cells divert through capillaries on their way from the marrow to the germinal centers could cause hairy cell leukemia mutations?  Hairy cellers are generally active, outdoor-types and tend to engage in activities that can result in excessive sun exposure.  White males with fair traits have the greatest incidence of classic HCL.  Likewise, HCLers have a higher incidence of basal cell carcinoma (BCC), another disease associated with people with fair traits and excess sun exposure.

      My HCL recipe:
          Ingredients:
               one part genetic disposition (fair trait genes)
                age
                excessive UVA/UVB or sunburn (or maybe high frequency RF since electrical engineers have 8x more incidence than most people)
           Directions:
                 Mix well until random RNA cytosine deamination causes a protein production train wreck and HCL-related gene translocations. 

Perhaps patients that have a durable remission beyond 15 years but then relapse aren't really relapsing, but instead have a new HCL mutation caused again by excessive sun exposure.  Sequencing and comparing the patients' HCL DNA at initial diagnosis and the later onset would determine if the relapse is a clone of the original occurence or derived from a new progenitor.

I wonder if the difficulty in sequencing my hairy cell DNA and generating a PCR primer might be due to an unusually rare cytosine deamination to uracil in my DNA (rather than RNA) that the DNA repair enzyme somehow freakishly failed to catch and repair.  I'm hoping they make some progress soon and can tell me what's different about my sequence.  Regardless, I'm exceedingly grateful for the opportunity to participate in the NIH clinical trial, and all the effort and help Dr. Kreitman and his staff have put into helping me.

Now that I've completed all the treatment provided by this trial, I'm in the watchful waiting stage -- anxiously looking forward to my next bone marrow biopsy and aspiration in June.  Hopefully this time, I'll be negative for hairies on all three tests -- peripheral blood, bone marrow and aspirate.

Wish me luck!

Hairy Cell Leukemia Trivia

Thought I'd put together a few trivia questions for those of you who want to test your hairy cell leukemia knowledge:

Questions:
1) What causes hairy cell leukemia?
2) Who discovered hairy cell leukemia?
3) In what year was hairy cell leukemia discovered?
4) Where was hairy cell leukemia discovered?
5) What is the formal name of hairy cell leukemia?
6) What protein is overexpressed on hairy cells and the main target of monoclonal antibody therapy?
7) What does the "CD" in "CD20" stand for?
8) Name the primary chemotherapies for hairy cell leukemia?
9) When is Pentostatin typically used in lieu of Cladribine?
10) What's the term for treatment with a monoclonal antibody (mAb)?
11) What is the primary mAb used to treat hairy cell?
12) What other surface proteins are also targeted in hairy cell?
13) Name a well known HCL immunotoxin?
14) Who is Ira Pastan?
15) What is the bacterial toxin used in HA22, and what's its origin?
16) What is the typical cause of fever after treatment with Cladribine (commonly misdiagnosed as "a mystery infection")?
17) What are the three modes of cell death mediated by Rituxan?
18) Who invented Cladribine?
19) Which is the more effective approach for administering Cladribine?
              5 day x 2 hour IV
              or 24x7 drip?
20) At what stage of cellular development is the malignant mutation of hairy cell believed to occur?
21) What is the median age of an HCL patient at diagnosis?
22) Is HCL more prevalent in men or women?
23) What type of cells are hairy cells from?
24) What is the average period of remission for HCL after Cladribine chemotherapy?
25) What percentage of patients receiving Cladribine have a complete remission, partial remission, and no response?
26) How rare is hairy cell leukemia?
27) What does MRD stand for?
28) Is there a cure for hairy cell leukemia?
29) The first case of patient/doctor genetic rights involved hairy cell leukemia and what university?
30) What's the life expectancy of the average hairy cell leukemia patient?
31) When should hairy cell leukemia be treated?
32) What is Hairy Cell Leukemia?
33) What is Bruton's Tyrosine Kinase (BTK)?
34) What Hairy Cell Leukemia (HCL) treatment options are available to multiply relapsed and refractory patients who don't respond to chemotherapy?

Answers:
1) Most cases of classic HCL have a BRAF V600E DNA mutation, caused by a photon from sunlight inducing an RNA translation error in a B-cell (a type of white blood cell) during replication.  This mutation is also common to 50% of melanoma cases, but in that case, it affects a skin cell.  The causes of other variants of HCL are unknown.
2) Bertha A. Bouroncle, MD
3) 1958
4) Ohio State University
5) Reticuloendotheliosis
6) CD20
7) "Cluster of Differentiation"
8) Cladribine and Pentostatin
9) When a patient's counts are so low or health is so weak that a less sudden drop in counts is needed; however, it is sometimes used if a patient doesn't respond to Cladribine.  Pentostatin is administered over several weeks whereas Cladribine is administered in 5 or 7 days.
10) mAb therapy
11) Rituximab (aka: Rituxan)
12) CD25, CD22
13) HA22
14) Head of NCI laboratory of molecular biology and immunotoxin development
15) Pseudomonas Exotoxin from Pseudomonas aeruginosa
16) Tumor Lysis (hairy cells dying)
17) Apoptosis (cell suicide), antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC)
18) Dr. Dennis Carson
19) Both are considered equally effective
20) Later in the differentiation process at the level of the germinal center B-cells, likely in the process of differentiating to a Memory B-cell (per Basso, et al, p.62, col 1).
21) 52
22) Men, by a ratio of 4:1
23)  B-cells, a type of lymphocyte.
24) Ten years.
25) 80%, 15% and 5% respectively.
26) HCL accounts for only 2% of diagnosed/reported cases of leukemia.  However, it may be more prevelant since it can remain "in-check" in many people without ever being diagnosed.
27) Minimal Residual Disease.
28) Not yet, but there are hairy cell clinical trials trying to establish a cure curve.
29) UCLA (link to court case)
30) The average patient will have a normal life expectancy.
31) In general, HCL should be treated when blood counts indicate one of the following conditions:
                 Platelets (PLT) < 100 K/uL
                 Hemoglobin (HGB) < 10 g/dL
                 Absolute Neutrophils (ANC) < 1.0 K/uL
       however, Dr. Michael Grever, in his paper "How I treat Hairy Cell Leukemia (Blood, 10/2009)" states the following:

                   "Therefore, I recommend that therapy be initiated when a declining trajectory predicts that the patient will reach a platelet count less than 100,000/uL or an absolute granulocyte count consistently below 1,000/uL."
32)  HCL is an uncommon, chronic, neoplastic (malignant) disorder of B lymphocytes (a type of white blood cell) that predominantly afflicts middle-aged men. The patient usually presents with pancytopenia (broad spectrum reduction in blood counts -- low platelets, low white blood cells, low red blood cells). In the U.S., there are 500 to 800 cases of HCL annually, representing just 2% of all leukemias. Although it is incurable, it is highly treatable, with an average remission of 10 years.
33) BTK is an enzyme that's critical to the maturation of B-cells.  Inhibiting it, with drugs like Ibrutinib, has proven to be a well-tolerated and effective means of targeting a variety of leukemias and lymphomas.  Clinical trials using Ibrutinib to target hairy cell leukemia in relapsed and refractory patients are now underway.
34)  Multiply relapsed and refractory Hairy Cell Leukemia (HCL) patients should consider the moxetumomab (moxe) clinical trial at NIH.  A majority of patients have achieved complete remissions and in many cases eliminated MRD.
 

Kinected

A lot has happened since my last post:

•        Christmas
•        New Years
•        Birthdays (Howard Recombinant DNA Experiment #1 turned 3, and my wife had a birthday too)
•        4 Rounds of Rituxan

The Rituxan treatments have gone well, although I've had to deal with several failed IV placements (including 3 blown veins).  The only significant change in my blood counts so far has been a dramatic increase in monocytes as shown below, but this has me very excited.  It's believed that monocytes may mediate the antibody-dependent cell-mediated cytotoxicity (ADCC) by Rituximab, and a cursory analysis of my counts leads me to believe this may be the case.  Specifically, my monocyte counts increased dramatically after both Rituxan treatments were initiated (see highlighted areas).

I believe this increase in monocytes is directly correlated to the administration of the Rituxan as they begin to kill the hairies through antibody attack (see picture below).  The monocytes increase in numbers as Rituxan (RTX) is introduced into the bloodstream and then they level off as they morph into phagocytes and ADCC is evoked.  As you can see in the highlighted areas above, the pattern for this cycle (RTX #2)  is similar to the first RTX treatment in 2009, but the initial level of monocytes is much higher.  Given that my spleen is now 40% of its prior volume (no longer infiltrated with hairies), and the monocyte level is 9 times higher than when I started RTX treatment #1, I think this round may have a much bigger impact in reducing the hairy cell burden in my marrow aspirate!  

Monocyte Mediated ADCC

Starting in week 5 of RTX treatment #1, my neutrophil level increased dramatically as the monocyte levels began to top off.  Hopefully, the same increase will occur over the next few weeks.  If so, I think the response correlation with RTX treatment #1 will be another strong indicator of monocyte mediated ADCC.  It may take awhile for it to complete the job, but fortunately Rituxan's half-life is two weeks, so it will remain in my bloodstream for months and during that time > 99% remains in the peripheral blood looking for B-cells and hairies to destroy, so it's readily available for quite awhile as the layers of the hairy clumps are peeled away.

Then again, since neutrophils are the first to attack (neutrophils are microphages, ie: small eaters), they may be pulled out of the peripheral blood stream to mediate Rituxan-induced complement-dependent cytoxicity (CDC) and attach to C3b proteins -- causing a drop in their blood levels.  Perhaps the monocytes are being released into my blood stream in response to the transient decrease in neutrophils. Monocytes are held in reserve in the splenic red pulp for just such an emergency.  As the monocytes morph into macrophages (ie: big eaters) to mediate ADCC induced by Rituxan, the neutrophils are no longer needed as much and stay in the blood and increase in numbers as marrow function improves. 

I watched the Dr. Najeeb lecture series on the complement system, and now I'm wondering if an overzealous complement system response to Rituxan aggregates immune complexes (Ig's, anaphylatoxins like C3a, mast cell activation products, etc.) in the skin that lead to the non-itchy rashes often seen in patients who take Rituxan.  I had several during my first round in 2009.  This cycle I noticed a small dime-sized one on my left arm a couple days after the first round that's still there.  They're small patches that usually take 5 to 8 weeks to clear.

Here's a video on Rituxan's mode of action that covers direct cell death, ADCC and complement.  However, the video indicates NK cells are responsible for ADCC whereas I'm postulating that monocytes may also play a significant role.

Rituxan Method of Action

My fascination with GA101 continues to grow.  It's a third generation monoclonal antibody (mAb) that mediates ADCC 5 to 100 times more effectively than Rituxan.  Not only is this antibody humanized, but it's elbow region has been engineered to provide better cross-linking of CD-20 antigens, which appears to dramatically improve apoptosis (cell suicide) as stated in a citation from a prior post.  This mAb has now undergone Phase II trials in indolent/refractory non-Hodgkin's lymphoma with very good results.  I'm lobbying and anxious for in-vitro studies to occur in HCL. 

[Credit: Robert Marcus, Kings College Hospital, London]

Aside from that, I've become quite a gadget geek.  I bought a PS3 to support my http://folding.stanford.edu/ hobby and an Xbox Kinect for working out.  It's seems to be doing the trick too.  My creatine kinase levels went from 109 to 315 over the past week.  CK is an enzyme that's secreted when you workout and convert ATP to ADP to release energy.  The Kinect is an imaging sensor that allows you to play games without a controller.  It's truly amazing.  The technology is still in its infancy, but you can use it to workout and keep/manage all your workout metrics, and it provides real-time analysis of your form that's better than a personal trainer's.  I predict it will make P90x obsolete within a year, and I'm anxious for a yoga application to be released.  I'm hoping some yoga and regular stretching will keep things fluid in my marrow and increase the hairy clump surface area to volume ratio, but that's just a WAG.  I figure it can't hurt.

I'm so grateful and glad I'm participating in the NIH clinical trial!  Not treating my somewhat difficult case with Rituxan by monitoring MRD would probably have led to more Cladribine treatments and marrow suppression.  I think that my case shows that just blindly adding Rituxan at 6 months post-Cladribine and taking a wait-and-see approach by monitoring counts to determine relapse is risky -- especially for younger patients.  Rather, monitoring and treating MRD is the way to go, and right now, only NIH has the facilities to do that -- especially the hypersensitive PCR MRD test.  Likewise, NIH provides 2 8-week cycles of Rituxan to treat MRD -- something regular oncologists won't be able to justify to insurance companies until the NIH study is completed.

The family's doing well.  My youngest (8 mo's) is already cruising and lifting herself up on tables, and the eldest is starting to read and play computer games (Dora and Cat in the Hat).  I've had a couple weeks as Mr. Mom over the past month while my wife's been on travel.  The first time was a breeze, but the baby had an earache the second time, so things were a little more exhausting.  I've been working on Ka-band science downlink designs for future Deep Space Discovery Missions and the S-band command and telemetry link for the GEMS program.  Overall, things are going well.
Happy New Year, and here's to a fruitful 2011!