Skip to content

Progression of mast cell diseases: Part 1

Among mast cell patients, we generally assume that a designation of SM means indolent systemic mastocytosis (ISM.) However, in research papers, this term can mean ISM, SSM, ASM or MCL. Advanced SM usually means ASM or MCL. These terms generate a lot of confusion in the patient population. When reading a paper, abbreviations are usually defined on the first page or within the introduction. It is important to check on what the researchers are using the term SM for.

As an example, let’s look at this really alarming quote to someone who thinks SM means ISM:

“The life expectancy of SM patients was shorter relative to age- and sex-matched controls. As initially observed by Travis et al, survival decreased rapidly after diagnosis: to 60% at 3 years, with a subsequent slower decline to 50% at 5 years. Beyond 5 years, the slope of the survival curve was similar to that of the control population. This observation confirms that the deaths in SM patients within the first 3 (and up to 5) years after diagnosis.” (Lim 2009)

In this paper, SM meant ISM, SM-AHNMD, SSM, ASM and MCL. When you average those survival rates together, you get a sharp decline in survival for the first five years. After that, it returns to normal, because most of the ASM and MCL patients in that study died by that time.

 

I get asked A LOT about whether or not ISM is progressive. I see a lot of people describe it as progressive. In medicine, progression usually means moving from one diagnostic category to a more serious one (like ISM to SSM.) However, a lot of patients use this term to mean a worsening of symptoms or disability while staying in the same diagnostic category (like ISM with mild daily symptoms to ISM with severe daily symptoms). Those are two different things. I’m going to answer both.

 

What is the life expectancy with ISM?

It’s normal.

“Patients with ISM have a favorable prognosis. These patients may suffer from mediator-release symptoms, but do not suffer from significant organopathy caused by MC infiltration.” (Valent, 2003)

In a study of 159 patients, 2.2% ± 1.3% died within five years of diagnosis, and 11% ± 5.9% died within twenty five years of diagnosis. “The majority of deaths in this ISM cohort were unrelated to mastocytosis.” (Pardanini 2013)

In a study of 342 patients, ISM was the largest subgroup with 159 patients.  They were significantly younger at presentation (median age 49 years.) “Overall median survival was not significantly different than that of the age and gender matched control population. Advanced age was the primary determinant of inferior survival.” (Pardanini 2013)

 

Will my ISM symptoms get worse with time?

There is really no way to know. In some people, they are stable, while in others, they fluctuate. However, mediator release symptoms (degranulation symptoms) are known to be more common in ISM than ASM and MCL.

“ISM patients can be highly symptomatic; in one study, 70% reported at least some degree of functional limitation, of which 17% reported severe limitation.” (Pardanini 2013)

“The type and severity of symptoms were independent of disease classification (CM vs SM), KITD816V status, and serum tryptase level.” (Pardanini 2013)

 

If my ISM symptoms get worse, does that mean I am progressing to a more severe category, like SSM, ASM or MCL?

No.

“One important aspect in this regard is that mediator-related symptoms per se are not indicative of aggressive mastocytosis unless accompanied by C-findings.” (Valent 2003)

“Moreover, organomegaly per se is not necessarily indicative of aggressive SM.” (Valent 2003)

“In fact, in a group of patients with SM, organomegaly is recorded over many years without impairment of organ function or development of C-findings.” (Valent 2003)

“The type and severity of symptoms were independent of disease classification (CM vs SM), KITD816V status, and serum tryptase level.” (Pardanini 2013)

 

References:

Pardanini, Animesh. How I treat patients with indolent and smoldering mastocytosis (rare conditions but difficult to manage.) 2013; Blood: 121 (16).

Pardanini, Animesh. Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management. 2013; American Journal of Hematology: 88 (7).

Pardanini, Animesh. Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. 2009; Blood: 114 (18).

Lim, Ken-Hong, et al. Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. 2009; Blood: 113 (23).

Valent, Peter, et al. How I treat patients with advanced systemic mastocytosis. 2010; Blood: 116 (26).

Matito, Almudena, et al. Serum tryptase monitoring in indolent systemic mastocytosis: association with disease features and patient outcome. 2013; PLOS One.

Sperr, Wolfgang. Diagnosis, progression patterns and prognostication in mastocytosis. 2012; Expert Review of Hematology: 5 (3): 261-274.

Valent, Peter, et al. Aggressive systemic mastocytosis and related mast cell disorders: current treatment options and proposed response criteria. 2003; Leuk Res 27 (7): 635-41.

Hauswirth, Alexander, et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. 2004; Leuk Res 28 (3): 249-257.