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By Marty Vanderlaan

Photo by: Dennis Schrader Photography | http://dennisschraderphoto.com

As previously shared, chest X-rays just before Christmas, showed that I had a 10 cm diameter mass in my lung. I had been following a premalignant condition (Waldenstrom macroglobulinemia [WM], a form of non-Hodgkin’s Lymphoma) with the “watch and wait” method for 20 years, and I was pretty sure this 10 cm mass was related to the WM disease. I was already seeing an oncologist, so mostly I just wanted to be transferred from the emergency room at the local ski hospital to my regular physician in San Francisco.

But of course, while I was making the connection between the mass in my lung and WM, it was far from proven. It could have been a primary lung cancer, or a metastasis from some distant tumor site. A total body PET scan showed no other hotspots, however. That turned out to be incredibly good news—no other sites of malignancy, anywhere, within the limits of the test.

For the most part, WM cells grow in bone marrow, where they produce serum IgM and gradually compete for and win over other bone marrow cells, leading to anemia. Occasionally, a clone of WM cells forms a focal proliferative disease in an organ, such as the lung. A biopsy showed the expected WM lymphoplasmacitic cells, but it also showed a nest of precipitated protein. LC-MS/MS analysis identified the protein to be lamda light chain and mu heavy chain, the two components of IgM secreted by WM cells. But why was this protein precipitated? Either the local concentration in the lung tissue was so high that the proteins were insoluble, or they were denatured and had precipitated as an amyloid deposit. Amyloidosis is a potential complication of WM (and other multiple myloma-related diseases). An abdominal fat biopsy showed amyloid light chain deposits in this tissue as well. Amyloidosis leads to progressive organ failure of the organs where the deposits occur—particularly vulnerable are the heart and kidney. So my aberrant WM clone was potentially life-threatening, but not from the malignancy per se, but rather as a consequence of widespread amyloid deposits. Although, there is no evidence that I have either heart or kidney damage, yet.

Treatment was with the B-cell lytic drug Rituxan, a drug I had helped develop at Genentech. My first infusion occurred just after New Year’s Day. I had read about first infusion reactions to Rituxan, a response to the large-scale lysis of cells resulting in a “tumor lysis syndrome.” But that familiarity did not prepare me to actually live through it. Rituxan is given intravenously, starting at a slow infusion rate, which is supposed to be gradually increased. At the first increase in flow rate, my heart raced, I started hyperventilating, and all of my muscles shook uncontrollably and violently. While I knew what was happening, I was powerless to control my body. I reached out to hold a hand, hoping human contact would calm my system, but to no avail. This reaction is known to the oncology nurses who were administering the Rituxan and an antidote was administered within a few minutes. I calmed back down.

The decision was made to continue the Rituxan infusion at the initial rate, without any of the planned flow rate increases—which was fine by me(!). But that meant the total infusion time took 18 hours. I want to thank those at Genentech who did the stability study showing that saline solutions of Rituxan are stable for up to 24 hours. I needed most of that time. Subsequent Rituxan treatments were given every 3 weeks, for a total of 6 treatments. But each infusion was proceeded with a relatively high intravenous dose of Benadryl, and there were no reactions to the later infusions.

One question I often get is how am I dealing with getting this life-changing diagnosis. Mostly I have reverted to my scientist persona. I follow all the statistics of my treatment, often graphing the trends. I follow blood counts (white cells, red cells, lymphocytes) and serum proteins (IgM, free light chains, hemoglobin, albumin). As someone with an oncology background (all be it with mouse tumors), I have a much different relationship with my physicians than most patients. I recently attended the international workshop on Waldenstrom macroglobulinemia (IWWM9) to further understand my treatment options.

There are times, however, when I am haunted by thoughts of my own mortality. I have cried at the unfairness of it all. Sometimes early in my treatments, when going to bed, I have wondered whether I would die in my sleep. Not a rational fear, but having looked into the abyss, one has such fears. I read the newspaper obituary pages with greater interest. Then I get back to plotting my data, reading the literature, blogging, and being actively involved in my own therapy.

Martin Vanderlaan, Ph.D. Analytical Chemist/Toxicologist from NYU Medical School. Recently retired after 20 years at Genentech, where he held a number of lab director positions, including head of Analytical Chemistry and Operations in the Process Development organization.