International Waldenstrom’s Macroglobulinemia Foundation

Language

Martin Vanderlaan: Celebrating 5-Years Post Stem Cell Transplant with a Wedding!

Martin Vanderlaan: Celebrating 5-Years Post Stem Cell Transplant with a Wedding!

 

With a small group of friends on March 20, 2022, we celebrated the 5-year anniversary of my autologous stem cell transplant (ASCT).  I say “we” since the last 5 years has been an adventure for both me and my fiancé (now wife), Linda.  Yes, we got married in July!  For a couple of 70-somethings, we have lots to be thankful for.

This essay is an update to my 2017 “Story of Hope” “Martin Vanderlaan: My Stem Cell Transplant for WM Amyloidosis.” In that story I gave credit for supporting me through the ASCT to my daughters and my girlfriend Linda.  We started dating about six months before my transplant.  We often joke with each other that it is only slightly exaggerating to say my pick line was “I am scheduled to have a stem cell transplant in six months.  Want to date?”  Linda says she had to decide in those six months whether she was “all in, or not”, and if she was “all in” that meant rearranging her life to spend a month with me in hospital isolation and another month on “house arrest” following the transplant.

The main reason for having an ASCT was that my WM had the complication of light chain amyloid deposit in my right lung and lower abdomen.  Because my wife had died 2 years earlier of cardiac amyloidosis, I was acutely aware of the threat that amyloid deposits can pose.  I had been treated with six cycles of Rituxan along with Velcade (a proteasome inhibitor), cyclophosphamide and dexamethasone, which had left me feeling much better. However, an ASCT was recommended as a necessary next treatment.

Going into the procedure I was hoping that the outcome would be that all the WM cells in my bone marrow would be gone, my IgM and free lambda light chains would be within normal range, and my “new immune system” would be free of WM.  However, I did not achieve such a complete “reset” on my bone marrow.  I still have WM, probably best described as “smoldering.” I have not required any “maintenance” therapies in the past five years beyond intravenous immunoglobulin therapy (IVIG) every 8 weeks.  One blessing of not being on any immunosuppressive therapy is that when COVID vaccines came along, I mounted a vigorous antibody response and so I participated in the Leukemia & Lymphoma (LLS) COVID study.

Since many of us closely follow the results of our serum test, I will give a brief summary of my past 5 years of clinical experience.  A post-ASCT bone marrow biopsy showing fewer than 0.5% Lymphoplasmacytic (LPL) cells. My hemoglobin has remained a little lower than I would like, and my IgM is higher.  But neither level has changed appreciably in 5 years, and they are not at levels that interfere with living.  Unfortunately, my lambda light chains have slowly and steadily increased from about 100 mg/L to about 400 mg/L.  These findings suggest I have two clones of LPL cells – one making IgM and one making Lambda.

The good news is that there is no evidence of any new amyloid deposition since my transplant.  My kidney function is fine (no protein in my urine), a recent echocardiogram showed “no change” in the past 5 years , and periodic PET-CT scans show slight shrinkage in the residual amyloid in my lung.  No new amyloid deposits (Hooray!).  Since amyloid is not the result of deposition of normal free light chains, but rather the deposition of denatured, insoluble light chains, maybe I am cured of those cells that were making aberrant light chains.

I have had a number of opportunities to give back to the community that has supported me on this journey.  Through the IWMF, I am the LIFELINE contact for amyloidosis and have communicated with several of you.  I am also on the IWMF research grant advisory committee.  I retired from 20 years working on drug development at Genentech, including being part of the team that brought Rituxan to the clinic.  I have returned to Genentech several times to give talks as “the voice of the patient” on what it is like to have both worked on, and later been treated with, Rituxan. Linda and I both volunteer in our Unitarian Universalist church community as Lay Chaplains, occasionally visiting with cancer patients, accompanying them to treatments, and in a few cases coaching on what to expect with their ASCT.

Although we had known of each other for several decades, Linda and I only really got to know each other when I was asked to host a fundraising dinner for the Unitarian Universalist Service Committee (UUSC), an international charitable organization that we both support. Since the dinner was to be catered, I decided I was in over my head and needed a co-host to help me and asked Linda. That led to the past five years of Linda and me getting to really know each other – living and learning through the ASCT and COVID, and getting to know each other’s extended families.  I have two daughters, and two granddaughters for Linda to get to know.  She has a son, and a new grandson, living in Brooklyn.  We have taken a couple of trips to NYC and extended one trip up the Hudson River to visit towns where my grandparents lived a century ago.

In pre-COVID 2019 we took an extended trip to The Netherlands and the UK to visit towns where our respective families had emigrated from. Nothing builds bonds like renting a car in England and driving through small rural villages on the left side of the road!  In the Netherlands, while renting a car the agent commented that we were planning a drive in the “Dutch high country.” “Dutch high country?” I inquired.  He replied that one of the reasons the villages were built where they were was that the land was a few meters higher than the surrounding farmland and therefore didn’t flood.

With COVID circulating there did not seem to be a time to gather a group of friends and celebrate our union.  After two years of COVID, we and our friends are ready for a party!  We got the same caterer that we used for the UUSC dinner to cater our wedding.  We had about 75 people at the ceremony, and no one caught COVID at the event.

We have just gotten back from a wonderful honeymoon, driving about 1800 miles over 4 weeks.  We drove up the coasts of California, Oregon, and Washington.  We spent time hiking in the California Redwoods and the temperate rainforest of the Olympic Peninsula.  Old growth Redwoods show scars of fires long ago, and inspired us with their resilience. For those of us who struggle to live a century, there is something humbling about standing next to a tree that has already lived twelve centuries.

One highpoint of the trip was driving to Hurricane Ridge in the Olympic mountains.  The road goes from sea level at Port Angeles to about 6,000 ft on the ridge over about 20 miles.  There we had spectacular views of mountain peaks and glaciers.

At some future point I may need additional treatments, but fortunately progress has been made developing new therapies for WM.  So, I will have options.  We were greatly heartened to read Arno Muller’s story of living into his 90s with WM and are looking forward to celebrating that milestone ourselves.  In the meantime, life is very good.

Martin Vanderlaan
San Francisco, California
October 2022

 

Marty’s Original Story of Hope- My Stem Cell Transplant for WM Amyloidosis

I had indolent WM for twenty years, but amyloid deposits in my lung hospitalized me eighteen months ago. I discuss my experiences with Rituxan, ibrutinib, and an autologous stem cell transplant (ASCT).

I am now 68 years old. 23 years ago, during a routine physical exam, my physician noted an unexpectedly high total serum protein level. The elevated protein was composed primarily of IgM, and lead to a diagnosis of Monoclonal Gammopathy of Unknown Significance (MGUS), which can progress to Waldenstrom’s Macroglobulinemia (WM). Over the next twenty years, my lab results never became alarming, and I was otherwise symptom-free and in good health. I changed jobs, moved cross-country, and my wife and I went about our lives raising our daughters. While “watchful waiting” was the correct strategy during those two decades, I was mindful of the potential for disease progression, and kept waiting for “the other shoe to drop.”

On New Year’s Day of 2014 my wife of 28 years died of cardiac amyloidosis. She had not been “feeling right” for several years, and was eventually referred to a cardiologist. But light chain amyloidosis is sufficiently rare that the correct diagnosis was made only in November, and by that time she was referred directly for a heart transplant. She died six weeks later, while still being worked up for the transplant. The best description I read of cardiac amyloidosis was that her heart was “starched”, sufficiently inflexible to no longer pump blood effectively even when beating. Because of this intimate acquaintance with amyloidosis and its devastating effects, and knowing that a subset of WM patients develop amyloidosis, I requested that my hematologist make monitoring my serum free light chain part of my routine blood tests, in addition to serum IgM.

I am a PhD analytical biochemist whose professional career has been in the biopharmaceutical industry, the last twenty years at Genentech. I tend to obsess on data, and have found that habit both professionally satisfying, and an emotional escape as my wife’s and my own illnesses unfolded. In July of 2015, the data from my lab results became progressively more concerning. Yet when my hematologist asked how I was feeling, I responded, “Great. I just got back from a week of hiking and bicycling at Lake Tahoe (elevation 6,300ft).” “OK”, he said, “see you in January.”

Just before Christmas I was again at Lake Tahoe, vacationing with my daughters and their families. One morning I awoke at about 4 AM, unable to get comfortable in any position in bed. My heart was racing; I had mild chest pains and some difficulty breathing. My daughters were adamant that I go to a local urgent care center. Once there, I was informed I was not having a heart attack, but should proceed directly to the local hospital Emergency Room. The urgent care doctor said, quite calmly, he would forward my chest X-ray to them, and “they will be expecting you.”  In lightly falling snow my younger daughter and I drove off to the hospital fifteen miles away.

In the ER I was informed I had a lung infection with bleeding, and a 10×14 cm (4 x 5.5 inch) mass in my right lung. The most immediately life threatening concerns were my infection (treated with antibiotics) and my blood loss (replaced with five units of blood). But being informed that one has a large, presumably malignant, mass in the lung was traumatic. As I had suspected, the biopsy showed the mass was mostly amyloid deposit, WM lymphocytes, and plasma cells. An abdominal fat biopsy also showed amyloid deposits, which indicated that these deposits were likely occurring throughout my body. The good news was that I showed no loss of cardiac or kidney function – so no amyloid damage to those organs, yet. My amyloidosis had been identified much earlier than my wife’s.

I was given six cycles of IV Rituxan at three-week intervals, combined with weekly Velcade, cyclophosphamide and dexamethasone. Ironically, Rituxan was the first drug I had worked on as a biochemist at Genentech. Some thoughts about getting a drug I had helped to develop are covered in a blog I wrote for the American Association of Pharmaceutical Scientists (see aapsblog.aaps.org/?s=Vanderlaan&search=Go(link is external))

All of this treatment occurred while both daughters had returned to their lives, well away from San Francisco, where I live and was being treated. Without local family to help during this five-month ordeal, I was able to marshal the assistance of friends using the website(link is external). I recommend this web tool to anyone facing a similar challenge where you would like to rely on friends to provide rides to infusions, an occasional home-cooked meal, conversation, or emotional support.

My last Rituxan infusion was in April 2016. By June my hemoglobin level and lung capacity both had returned to near normal, and gradually I built up the endurance to walk about five miles a day in my hilly neighborhood. A bone marrow biopsy showed about 10% abnormal lymphocytes and plasma cells, and my serum IgM and free light chain remained high. The decision was made to start me on oral ibrutinib, which, in the published literature, shows promise for WM patients with the common WM genetic mutation that I have.

During the oral ibrutinib treatment I suffered no side effects. I felt well enough to take a five-week vacation in Europe with my younger daughter, as a belated college graduation present to her. This trip was a treasured parent-adult child bonding for the two of us, especially since she had lived through her mother’s death and my hospitalization two years later, both related to amyloidosis. We also scheduled our trip to be in Amsterdam to coincide with the International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-9), which I attended.

By January 2017, unfortunately, it became obvious that the ibrutinib had not had its desired effect of lowering my IgM and light chain. I suffered another lung infection, and a total body PET-CT scan showed that the mass in my lung was approximately the same size. In addition, a similar mass – assumed to be an amyloid deposit – was noted in the soft tissue of my lower abdomen near my pancreas and kidneys. The danger that this might progress to amyloid deposits in my organs was very concerning, and my physicians and I agreed that it was time to take the next step and prepare me for an autologous stem cell transplant (ASCT).

I will go into detail on the ASCT process for the benefit of readers who might be considering this treatment. Over three days in early March I received abdominal injections of Neupogen (also called G-CSF or filgrastim) followed by a single injection of another drug called plerixafor to cause the stem cells to proliferate to the point that they spill out into the blood stream. I shaved my beard, and had my hair cut “military short” in anticipation of my hair falling out. I mentioned to the nurse managing my case that the ASCT was now becoming very real, after all the preliminary testing. Her wise reply was that I should focus on the destination, not the journey. While the next few weeks would be rough, I would arrive at “a better place” and that should be my guiding thought in enduring the procedure.

The next step in the treatment was to harvest my stem cells from my blood stream. This began with having a tube or catheter inserted into the jugular vein in my neck, leaving a rather odd protrusion of tubes for external connections. The next day I spent about eight hours hooked up by these tubes to a device that separated stem cells out from my whole blood then returned the remaining components of my blood to my body. The total amount of blood so processed was about three times my total blood volume. At the end of the day the resulting bag of stem cells was sent off to the lab to get a stem cell count and to be frozen in liquid nitrogen.

The hospital staff informed me that the minimum number of stem cells they needed for the stem cell transplant was two million stem cells/kg body weight, but that an ideal number would be five million or more. My count for the first day of harvest was three million/kg, so another round of harvesting was planned for the next day – another eight hours on the machine. To my surprise and disappointment, that second day yielded only another 950,000 stem cells/kg. With this drop-off in collection on the second day, it was decided not to collect on additional days. In the background of my mind was the fear, “what if they don’t have enough?”  After all, it was these cells that I would depend on for recovery.

I was admitted to the University of California, San Francisco’s transplant ward. My first evening there I was given melphalan by IV over about thirty minutes. This is the drug used to kill your bone marrow cells to prepare for the transplant. It also kills other fast-growing cells such as those in your intestines, skin, and hair follicles. I was advised to suck on chipped ice starting fifteen minutes before and continuing through fifteen minutes after the infusion. The cold causes the tiny blood vessels in your mouth to contract, minimizing the melphalan dose to the mouth tissues and thus reducing the risk of mouth sores developing later while you are immune-suppressed. Since the total time for the chipped ice and melphalan is about an hour, I advise patients going through this procedure to have planned something else to focus on for this period. In my case, my daughter and I pulled out our phones and reviewed pictures from our Europe trip. It was a wonderful distraction, a reminder of better times, and kept my mind off of what was dripping into my vein.

The next day was unquestionably the worst day of the entire procedure. My nausea was such that even moving from the hospital bed to an adjacent chair was an ordeal. This day allowed the melphalan to clear from my system.

A day later, it was time to infuse my stem cells. A machine with the bags of cells was brought to my bedside. Individual bags were gently thawed and then given to me by IV. As each bag was being given, the next bag was being thawed so no bag remained thawed for more than a few minutes before being dripped into my vein.  Several hours were taken for this process on the first day, with the process being repeated on the next day until all of the stem cells that had been collected were returned to my body. The idea was that they would then find their way to my bone marrow and “set up shop” for healthy blood cell proliferation and immune system fortification. The day you begin re-infusing your stem cells is considered “day-zero” in the ASCT process, i.e., the “birthday” for your new immune system. This “birthday” was celebrated with a surprise birthday cupcake and candle from the nurses.

Over the next few days I responded to the anti-nausea medications and was able to eat a bit. Daily blood cell counts were posted on the whiteboard visible at the foot of my hospital bed. Gradually the remaining pre-transplant white and red blood cells, platelets, and neutrophils diminished to near zero. “Come on stem cells, start replacing these dying cells,” I thought. My hair fell out. My energy level fell. By about the fifth day post-transplant, the neutrophil count – the cells most important for my immune system to begin protecting me again – increased slightly. “OK, one day does not a trend make, but it is a basis for hope,” I thought. Over the next few days all the cell counts increased steadily, slowly, each day rising higher than the day before. “Maybe, just maybe, this whole process is working for me the way it has been described, and my stem cells are rescuing me.” This is not to say that there were not complications. As is not unusual, I needed a couple of units of blood to offset my anemia, and there were frightening episodes of fevers that luckily – and thanks to all of the hospital’s precautions – did not blossom into serious infections. And I was exhausted.

I spent 21 days in the UCSF transplant ward, and then a month at home under “house arrest”. My gradual recovery in both places was greatly facilitated by the loving care given to me by my younger daughter and my girlfriend. Both took time off from their jobs to be with me for the seven weeks. Having two caregivers allowed them to balance being with me and their own lives. Anyone planning a stem cell transplant should be sure to plan for adequate assistance.

I learned that recovery from ASCT seldom is linear, and found the backward steps to be frustrating and depressing. Each patient has unique experiences during ASCT recovery and mine might not be reflective of what others experience. In looking for the source of the possible infections during the fever spikes, total abdominal CT scans were performed. While no infection site was ever positively identified, a doubling in size of the previously noted abdominal mass was incidentally noted. This led to some frightening questions: How could something be growing when I just had high-dose melphalan? Was the hypothesis that this mass was an amyloid deposit valid? The last thing I wanted was another kind of cancer. The biopsy results came back, indicating amyloid deposit, inflammatory cells, and a few WM cells. Somehow the timing of my ASCT had coincided with a large deposition of amyloid proteins in the soft tissues of my abdomen.

Lying in bed gives one lots of time to speculate. Supposing the abdominal amyloid deposition had preceded the one in my lung eighteen months ago? My vague bloated feeling and dull pain in my back around my kidneys might well have been misdiagnosed by me as something intestinal – probably chalked up to something I ate. Or I might have thought it to be mere back-muscle strain. My odyssey of treatments might not have begun until something more serious had happened.

The three-month post-transplant period involved more extensive testing. A bone marrow biopsy showed that the abnormal cells were not at zero but were down almost 100-fold from my pre-transplant value. And the abdominal CT showed that the abdominal mass had shrunk an amazing 80%. The scientist in me is still analyzing and puzzling over the large personal data set I have collected for serum IGM, free light chain, and other test data under conditions of various therapies. Expected correlations of values are often not there, and I speculate about multiple sources of these values. I wonder whether there are separate clones producing these serum proteins, each clone with its own dynamics. Or maybe the amyloid deposits are non-cellular reservoirs that can provide a source for serum proteins. Or maybe differences in clearance rates obscures differences in production. I would be more than happy to discuss any of this in detail with those of you who share this interest and curiosity. In spite of these questions, I am relieved that the current findings are largely positive.

My overall energy level is back nearly to the level of last fall and my hair is growing back. I am walking 4 – 5 miles a day. It is time to go back to the mountains of Tahoe, and immerse myself in the forests. This winter had quite heavy snows, and the streams are flush with snow-melt. Spring has come and gone, the wildflowers are in full bloom, and all the trees show vigorous green new growth. So it is for my stem cells. They, too, are recovering from their winter of liquid nitrogen, and are showing vibrant growth, celebrating a new spring of proliferation and differentiation. Life is good.

Martin Vanderlaan
San Francisco, California
August 2017