By Marty Vanderlaan
Twenty years ago, while getting a routine physical, the physician noted that I had high total serum protein. He suggested we investigate and determined that I have serum IgM at about 25 mg/mL (normal for an adult is less than 2.6 mg/mL). The IgM was not high enough to increase the viscosity of my blood, which is a frequent clinical manifestation of IgM levels above 40 mg/mL. The diagnosis was Waldenstrom macroglobulinemia (WM), a rare “premalignant” form of non-Hodgkin’s Lymphoma, where plasma cells fail to die as a consequence of normal apoptosis. In any given year, about 1% of WM patients progress to multiple myeloma. So I followed my serum IgM levels every 6 months, and my oncologist and I watched and waited. Normally, the WM malignant cells are preferentially localized in the bone marrow, causing mild anemia in my case. Along with elevated serum IgM levels, there was a concurrent decrease in serum IgG and IgA (decreasing my body’s ability to fight infections), and elevated in serum free lambda light chain.
Two years after my wife died, I was hospitalized with pulmonary hemorrhage and lung infection, and X-rays showed a 10 cm mass in my right lung. A biopsy showed immature plasma cells and a mass of precipitated protein. Peptide analysis by mass spectrometry showed the protein was IgM (µ heavy chain and λ light chain). The malignant cells had secreted it at a high enough local concentration that this normally soluble protein had precipitated. One manifestation of WM disease progression is a focal form, where plasma cell proliferation occurs in an organ such as the lung. A complication in my case was the localized amyloid deposition of the plasmacytoma proteins.
The critical question was whether the amyloid plaques were systemic and not just localized to my lung; in systemic amyloid, the deposition of light chains has the potential to damage multiple organs and was what had killed my wife. Further biopsies of my fat and bone marrow showed amyloid deposits. Fortunately, organ function tests show that I do not yet have damage to my kidneys, liver, or my heart, but those problems could only be a matter of time. My lung capacity, however, was severely reduced.
I have been treated with Rituxan in combination with Velcade, cyclophosphamide, and dexamethasone to reduce the cellular mass in my lung, and to reduce the WM cells producing potentially lethal proteins that form amyloid. The cellular part of my tumor mass has been greatly reduced. The protein part is expected to slowly resolve as macrophages remove the amyloid. It’s six months later, and my lung capacity has largely returned. Through flow cytometry, I know that I have no circulating plasma cells or B-lymphocytes. However, about 5% of my bone marrow cells remain the WM plasma cells, and my serum IgM and free light chain levels remain elevated, although not as high as before. I am now being treated with ibrutinib to see if these levels can be reduced (more on that therapy later).
Light chain amyloid disease is described as rare, but both my wife and I have had it. We have daughters, and I seek to advise them on whether this is a familial trait. My better outcome can be attributed to an astute primary care physician following up on my high serum protein 20 years ago. What we with amyloid disease and/or Waldenstrom macroglobulinemia wish to do is to raise clinical awareness of these diseases. My wife might be alive if her diagnosis had been made years earlier.