It's very interesting that you mentioned the MGUS, the monoclonal gammopathy of unknown significance because the cases of multiple myeloma, a blood cancer, usually are preceded by monoclonal gammopathy of unknown significance. However, it's important to emphasize that not all patients with MGUS will develop multiple myeloma. On the other hand, most patients with multiple myeloma had MGUS in the past. So, MGUS is a very interesting condition. How do people usually find out that they have an MGUS? Because they tend to bleed, have they been discovered to have an acquired form of von Willebrand disease? MGUS is a very interesting medical condition.

You explained it very well. The situation with MGUS, as I said, originally MGUS was called benign monoclonal gammopathy. MGUS is called 'of uncertain significance' because 1% per 100 patient-years may develop multiple myeloma. They are also way too unpredictable; it is not easily predicted who will develop multiple myeloma. Sometimes if MGUS is discovered by chance, as you know, by carrying out, for instance, serum electrophoresis, for the sake of example, in this country, but I also think in other countries. To receive a referral to do radiology testing, you need to have some examinations, including serum electrophoresis. So MGUS is discovered, particularly in older people, often by chance. But as you mentioned, sometimes acquired von Willibrand disease is diagnosed because usually, it doesn't give any signs. MGUS is discovered by chance because until MGUS evolves, which happens very seldom, as you mentioned, towards multiple myeloma, they have no signs, and a patient is perfectly well.

But sometimes, the problem is, as you mentioned, the consequences, such as the appearance of acquired von Willibrand syndrome. I'm not saying that is a frequent cause of diagnosis of MGUS [monoclonal gammopathy of unknown significance]. The much more frequent situation is when the patients with MGUS are diagnosed by chance during a routine exam. It may be ordered for a checkup or need a blood test to carry out some radiological exams. Usually, they are asymptomatic of the problem [monoclonal gammopathy of unknown significance]. We don't know very clearly who will progress to multiple myeloma usually. MGUS of IgA type tends to progress to multiple myeloma more frequently. But so that patients with MGUS of IgA type need more frequent monitoring. But usually, I recommend monitoring. By the way, I see very many of these patients [with monoclonal gammopathy of unknown significance]. As usual, I tend to reassure them, I don't do diagnostic test exams more often than once a year, particularly if they are over a certain age. Certainly, the problem is when patients with MGUS are younger, say, 50. Because then, of course, the likelihood, just as a matter of time, for MGUS to progress to multiple myeloma is by definition more likely. It is simply because they have a longer life expectancy. Patients in their 60s, 70s, 80s usually have no treatment for them. They don't deserve any treatment. Not all patients with MGUS, of course, have acquired von Willibrand syndrome. But, for instance, I've recently seen a young man who has a myeloproliferative disorder. And that was discovered because of the acquired von Willibrand syndrome.

Especially in the younger age, there are several indicators for the MGUS progress.

Patients with MGUS at a younger age have a worse prognosis simply because of more likely to be exposed to the risk. That is only a matter of statistics.

Right, because the clone of blood cells grows for a longer time.

Yes, because life expectancy is different from the levels seen in 60-70-80-years-old patients.