Medication Summary
The tyrosine kinase inhibitors (TKIs) midostaurin, imatinib, and avapritinib have each been approved by the US Food and Drug Administration (FDA) for various types of mastocytosis. [16, 13, 63] Other agents are used for symptomatic relief, including prevention and treatment of anaphylaxis.
Antineoplastics, Tyrosine Kinase Inhibitor
Class Summary
The tyrosine kinase inhibitors midostaurin and imatinib have each been approved by the FDA for various types of mastocytosis. A case report of ruxolitinib, a Janus Associated Kinase (JAK) inhibitor, was shown to improve symptoms and quality of life a patient with systemic mastocytosis.
Midostaurin (Rydapt)
Midostaurin has demonstrated the ability to inhibit KIT signaling, cell proliferation, and histamine release and induce apoptosis in mast cells. It is indicated for adults with advanced mastocytosis which includes aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
Imatinib (Gleevec)
Imatinib is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF-and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-kit mutation. It is indicated for adults with aggressive systemic mastocytosis without the D816V c-Kit mutation as determined with an FDA-approved test.
Avapritinib (Ayvakit)
Avapritinib is a tyrosine kinase inhibitor that binds to and inhibits specific mutant forms of PDGFRα and c-Kit, including the PDGFRα D842V mutant and various KIT exon 17 mutants. This results in the inhibition of PDGFRa- and c-Kit–mediated signal transduction pathways and the inhibition of proliferation of tumor cells that express these PDGFRa and c-Kit mutants. It is indicated for treatment of adults with advanced systemic mastocytosis (AdvSM), which includes aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. It is also indicated for adults with indolent systemic mastocytosis (ISM). Not recommended for treatment of patients with AdvSM or ISM with platelet counts 9</sup>/L.
Sympathomimetics
Class Summary
Sympathomimetic agents are used in the treatment of anaphylaxis.
Epinephrine (Adrenalin, Bronitin, EpiPen)
Drug of choice for treating anaphylactoid reactions. Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects of epinephrine include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Mast Cell Stabilizers
Class Summary
Mast cell stabilizers prevent release of mediators from mast cells, which cause airway inflammation and bronchospasm.
Cromolyn sodium (Intal, NasalCrom)
Inhibits degranulation of sensitized mast cells following their exposure to specific antigens.
Corticosteroids
Class Summary
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant for the treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear neutrophil activity. Has been used in patients with systemic mastocytosis to control malabsorption, ascites, and bone pain and to prevent anaphylaxis
-
Systemic mastocytosis. Bone marrow aspirate, Romanowsky stain, high-definition magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a bone marrow smear from a patient with systemic mastocytosis. Several mast cells are present in this photograph. These mast cells are larger than normal mast cells and have more irregularly shaped nuclear outlines and less densely packed mast cell granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
-
Systemic mastocytosis. Bone marrow aspirate, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a toluidine blue stain of a bone marrow smear from a patient with marrow involvement by systemic mastocytosis. Five mast cells are present in this field. The mast cell granules are metachromatic with the toluidine blue reaction. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
-
Systemic mastocytosis. Bone marrow biopsy, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cell infiltrate. This is a toluidine blue stain of a bone marrow biopsy from a patient with systemic mastocytosis. The mast cells are metachromatic with toluidine blue and contain numerous purple granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
-
Systemic mastocytosis. Lymph node biopsy. Diagnosis is mastocytosis, morphology is mast cell infiltrate, and the organ is the lymph nodes. This is a lymph node biopsy from a person with systemic mastocytosis. The mast cells have a characteristic perifollicular distribution. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
-
Systemic mastocytosis. Lymph node biopsy, chloroacetate esterase stain. Diagnosis is mastocytosis, and morphology is mast cell infiltrate. This is a portion of a lymph node biopsy from a patient with systemic mastocytosis. The mast cells are chloroacetate esterase positive, which is characterized by an orange granular appearance. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
Tables
| Criteria | WHO | ICC |
|---|---|---|
| Major Criterion | Presence of multifocal and dense infiltrates of mast cells in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. | Presence of multifocal dense infiltrates of tryptase- and/or CD117 positive mast cells detected in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. |
Minor Criteria |
Spindle shape or atypical mast cell morphology (type I or type II) in 25% or more of the mast cells in biopsy sections of bone marrow or other extracutaneous organs | Spindle shaped or atypical immature morphology in more than 25% of mast cells in biopsy sections of bone marrow or other extracutaneous organs |
| Minor Criteria | Presence KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ |
Presence of KIT D816V mutation or other activating KIT mutation in bone marrow, peripheral blood, or other extracutaneous organs |
| Minor Criteria | Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
| Minor Criteria | Serum/plasma total tryptase levels persistently greater than 20 ng/mL | Serum tryptase level persistently greater than 20 ng/mL. In cases of SM-AMN an elevated tryptase does not count as a SM minor criterion. |
