There isn’t a lot of data on death from mast cell disease. Not real data, with statistics and numbers. People with SM and MCAS are frequently reassured that they will live a normal life span. People with SM-AHNMD are quoted an average survival of about 8.5 years; ASM, 3.5 years; MCL, under a year.
Of those groups, only the survival time for mast cell leukemia is convincing to me. This is because mast cell leukemia has a pretty homogenous presentation, meaning that it affects most people in the same way. When a disease is as rare as MCL, it is important that you remove as many variables as possible in order for the data to be sound. And that’s the problem with the rest of the survival data, to my eyes – there’s just too much variability. Throw in a patient population as small as ours and you’ve got a lot of uncertainty.
The effects of mast cell disease are highly individualized. There are several B and C findings, meaning that combinations of symptoms and manifestations are very variable. The SM-AHNMD group is a good example of this. This category lumps together many different combinations of diseases, not to mention the stages of those diseases. Someone with ASM-AML is going to have a very different prognosis than someone with SM-CEL. Simply averaging the lifespans of these people and quoting this as a life expectancy does the mast cell community a disservice. It is important to remember this when you are typing “mast cell disease death” in the middle of the night.
Even though we know that most people with SM die from something else, or that for many people, it is a very manageable disease, there is always the possibility that it will be different for you. It’s hard not to imagine that you will be in the unlucky percentage of people that have progressive disease, that develop ASM, that have leukemic transformation. Admonishing people who bring up this concern as “negative” or “paranoid” doesn’t make it less terrifying. It just makes people more afraid to talk about the fact that sometimes people die from mast cell disease and often they aren’t sure how best to minimize their chances of becoming one of them.
Due to the differences in presentation, it has been difficult to identify markers that definitively indicate prognosis. A lot of effort was put into looking at various CKIT mutations, not just D816V, to see if this could be predictive. There has not been statistically significant data that this is the case.
The closest things we have to prognostic markers don’t get a lot of play in the general mast cell consciousness. We talk a lot about CKIT because it affects treatment, and symptoms because it affects diagnosis. But beyond the initial workup, we don’t often hear much about the CD2 and CD25 markers. However, a paper published in 2009, established a link between “immunophenotype,” in this case which markers the cells present, and prognosis.
This study looked at bone marrow samples from 123 patients with different types of SM, including MCL. Importantly, they also had a large control group of people who did not have SM. A solid control group is key to determining that a finding is real. They defined the patients as either good-prognosis (SM, well differentiated SM, and cMAD, clonal mast cell activation disorder (what we now call monoclonal mast cell activation syndrome, MMAS)), or poor-prognosis (ASM and MCL.)
They determined that for patients whose mast cells expressed BOTH CD25 and CD2 (ISM/MMAS) or NEITHER CD25 and CD2 (WDSM), prognosis was good. However, mixed expression (typically CD25+ and CD2-) indicated a poorer prognosis. They compared it to current markers, like the D816V mutation and serum tryptase, as well as clinical findings, like swollen spleen, swollen liver, skin lesions and white blood cell count. The expression of markers was found to be a sounder method for estimating life expectancy than any of these.
It’s okay to be scared. We all know people who have died from mast cell disease. It is scary to think that we could be next. It is scary to live under the looming threat of anaphylaxis. But the good news is that science is trying to catch up. More people are being diagnosed with mast cell disease, and science is getting better at identifying the ways that we are alike and different. There is every reason to think we will have comforting data in the future. We just have to get there.
Teodosio, Cristina, et al. 2009. Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes. Journal of Allergy and Clinical Immunology, 125: (3), 719-726.