It's Been Awhile...

It's hard to believe my last post dates back to July, 2011.  So much has happened since then.  Shortly after my last post, I experienced a significant drop in a type of white blood cell known as neutrophils, which I attribute to an effect known as Rituxan-related late-onset-neutropenia (LON).  I quickly recovered with the help of the expert staff at NIH, where I am being treated.  The neutrophil count of 700 that I alluded to in my last post was just the beginning.  I dipped all the way down to 0 but recovered quickly with the help of neupogen (aka: Neulasta), a hormone that induces the marrow to produce neutrophils.  Everything worked out fine in just a few days.  I'm grateful for everyone at NIH who treated me and helped me recover.  They are fantastic!

Otherwise, I've been working hard and just enjoying life.  Great progress has been made with respect to early treatments using Vemurafenib  (aka PLX-4032), the BRAF V-600E inhibitor that targets the mutation specific to nearly 100% of hairy cell classic cases.  UVA rays from sunlight induce the mutation (the same one that causes 50% of melanoma cases).  In other words, the cause of hairy cell leukemia is sun exposure.  A refractory patient in Germany was the first I know of to receive Vemurafenib, and now a patient in England -- an incredibly courageous individual who has seen more hardship over the past two years than I can imagine.  He's a pathfinder and an inspiration to many of us.  Both patients had given up hope of achieving a meaningful remission with the known chemotherapies (Cladribine, Pentostatin, and Bendamustine) and tried the Vemurafenib as a last hope.  I believe one of them got down to a platelet count of 10 (out of 160,000) when he started treatment.  This new drug appears to be working well -- melting away the refractory hairy cells, and also is being investigated to treat papillary thyroid cancer, which is also associated with the BRAF V600 mutations (thus probably caused by excess UVA exposure). 

NIH is preparing to start a trial in March, 2013 for refractory and relapsed patients that will investigate two other BRAF V600 inhibitors to treat HCL.  I will post a link to that trial and protocol when it becomes available.  Interested individuals should contact Dr. Kreitman at NIH. He always welcomes direct calls from patients (see his number in the blog sidebar). 

Personally, everything is well with me.  My counts are still great, and I had a peripheral blood flow cytometry test last week which was negative for hairy cells.  My last bone marrow biopsy was in June, 2012.  The core was negative for hairy cells, and the aspirate only showed 0.08% hairies, if I recall correctly.  I've started rowing 2 to 4 miles every day and hope to join a local rowing club soon.  The only daily supplement I take is 1000 IU of Vitamin D in the winter and early Spring.

I continue to highly endorse NIH for both new and refractory/relapsed patients.  The Cladribine + Rituxan trial has had a 100% remission rate for new patients (over 70 now), which is amazing.  I know I'd be in a very different position right now had I not received both rounds of Rituxan when I did -- to treat minimal residual disease instead of relapse.  My participation in the trial made all the difference in the world between achieving a CR (complete remission) and being among the 20% of patients who do not with just standard chemotherapy. 

All first time HCL patients should call Dr. Kreitman at NIH to discuss treatment options and submit research samples before proceeding with treatment, regardless of whether they decide to seek treatment at their local hemoncologist or NIH.

Just one more thing:  Here is a link to 15-year-old Jack Andraka's TED talk.  At 3-cents, his carbon nanotube antibody-based sensor (patent pending) costs 1/26000th that of the $800, 60-year-old ELISA test for pancreatic cancer and is 100 times more sensitive.  The possible applications cover a broad spectrum -- from water contamination to HIV detection, and will improve the lives of billions.  He's showing us that innovation can bridge the gap between providing services and cutting costs.  Glad Intel and the school systems are still supporting and promoting science fairs.  This is one helluva return on investment!!!


Happy New Year to All!

- Jon

Here are some articles related to the BRAF V600E mutation and HCL Classic:

The BRAF V600E Mutation in Hairy Cell Leukemia

BRAF Inhibition in Refractory Hairy-Cell Leukemia

 

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!!!