What is the risk of disease progression (to SSM/ASM) with ISM?
From 5-10 years after diagnosis, 1.7% (± 1.2%) showed disease progression. From 20-25 years after diagnosis, 8.4% (± 5%) showed disease progression. (Pardanini 2013)
“Overall risk of transmission to acute leukemia or ASM [from ISM] was low (<1% and 3%, respectively).” (Pardanini 2013)
In a study of 74 ISM patients, 8% progressed to SSM and 4% progressed to ASM. (Matito 2013)
How is ISM different from more severe categories?
“Advanced systemic mastocytosis (ASM, MCL) is marked by uncontrolled accumulation of neoplastic mast cells (MCs) in various organs with consecutive impairment of organ function, drug resistance and poor prognosis.” (Valent 2010)
In ASM and MCL, mast cells permanently disrupt the function of organs and can cause organ failure. The risk of death is independent of anaphylaxis.
“In patients with ASM, significant organopathy due to MC infiltration is found (C-findings).” (Valent, 2003)
“In contrast to ISM, patients with ASM often present without maculopapular skin lesions.” (Valent 2003)
“Mediator-associated problems occur quite frequently in ISM but are also seen in patients with advanced SM. However, in the latter group of patients, the predominant clinical problem is usually not related to mediator-associated symptoms but to the proliferation and often aggressive growth of MCs in diverse organs leading to organomegaly or organopathy, or even organ failure, also referred to as C-findings. “ (Valent 2010)
“ISM is predominantly characterized by symptoms related to mast cell degranulation/ mediator release/ and/ or allergies or anaphylaxis. In contrast, aggressive mastocytosis variants (aggressive SM, mast cell leukemia) are characterized by organ dysfunction related to mast cell infiltration.” (Pardanini 2013)
I have SSM, does that mean I will definitely get ASM?
“In most patients with SSM, the course remains stable over years or even decades. For these patients, we recommend to wait and watch B-findings, including the serum tryptase level, which is a reliable marker of monitoring of (S)SM even when levels are highly elevated.” (Valent 2010)
How is SSM different from ISM?
SSM is usually diagnosed at a later age, with an average of 64 years old.
“SSM patients also displayed significantly higher incidence of constitutional symptoms (45%), anemia (55%) and mast cell mediator levels. Average survival of SSM is 120 months. In a multivariate analysis, advanced age was the primary determinant of inferior survival and accounted for the marked difference in survival [for] SSM.” (Pardanini 2013)
“The risk of disease progression and leukemic transformation (18% in SSM) may be higher in SSM as compared with other ISM subgroups. The significantly inferior overall survival of SSM patients was largely accounted for by their older age.” (Pardanini 2013)
I have ASM, does that mean I will die within 41 months?
No. ASM is now recognized to have two predominant courses of disease. The first is ASM with slow progression. The second is ASM with rapid progression. Survival is dependent on a great deal of things, including mast cell burden and which organs are involved. Moreover, the 41 month mean survival did not include large patient groups treated with midostaurin, which shows more efficacy in these patients.
“Patients with ASM can show a slowly progressing or a rapid clinical course. Rapidly progressing ASM may also shift into another category of SM, ie MCL or (A)SM-AHNMD within short time.” (Valent 2003)
“An important of ASM is that the disease can present as slowly progressing ASM (similar to SSM but with C-findings) or rapidly progressing ASM. The latter may behave like MCL and can progress to frank MCL within a short time. Another important aspect is that, during progression of ASM and MCL, the KIT mutant D816V may disappear.” (Valent 2010)
“Many patients with ASM with slow progression can be kept under control for several months or even years by interferon-a or 2CdA [cladribine].” (Valent 2010)
What is the risk of leukemic transformation (developing MCL or AML from a pre-existing mast cell disease)?
In a cohort of 342 patients with some type of SM, 1/159 (0.6%) ISM patients, 2/31 (6.5%) ASM patients and 18/138 (13%) SM-AHNMD patients underwent leukemic transformation. (Lim 2009)
“Overall risk of transmission to acute leukemia  was low (<1%) .” (Pardanini 2013)
Is it possible for your disease to convert to a less severe category (like SSM to ISM or ASM to SSM)?
Yes. When evaluating treatment options for ASM and MCL patients, responses to treatment are classified as major response (disappearance of C findings), partial response (partial resolution of C findings), or no response. Some studies also include a minor response option.
In 2003, Peter Valent reported a 21% major response in ASM to interferon-a with or without steroids. (Valent 2003)
This link here details major and partial response rates to midostaurin in a patient group with ASM or MCL: https://ash.confex.com/ash/2012/webprogram/Paper51749.html
SSM patients with persistently refractory symptoms and/or upward trending tryptase often receive interferon-a or cladribine. I have received patient reports that it “knocked [them] back to ISM.” I have not as yet found a literature source for this phenomenon.
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.