New approaches to therapy for mastocytosis - A case for treatment with kitkinase inhibitors

Citation
Bj. Longley et al., New approaches to therapy for mastocytosis - A case for treatment with kitkinase inhibitors, HEMAT ONCOL, 14(3), 2000, pp. 689
Citations number
22
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
ISSN journal
08898588 → ACNP
Volume
14
Issue
3
Year of publication
2000
Database
ISI
SICI code
0889-8588(200006)14:3<689:NATTFM>2.0.ZU;2-X
Abstract
There is currently no cure for mastocytosis. The treatment of mastocytosis is generally conservative and symptomatic and is designed to prevent or ame liorate the deleterious effects of mast cell mediators rather than to elimi nate the mast cells which produce and release them.(9) Thus, management of mastocytosis begins with educating the patient to avoid specific factors th at can cause the release of mast cell mediators and the symptomatic respons es to them. Direct therapeutic intervention is tailored to the symptom comp lex of individual patients and consists mainly of drugs that block histamin e receptors. Blockage of H-1 receptors has some efficacy in controlling cut aneous symptoms such as flushing and itching, and H-2 antagonists are used to prevent and treat histamine-induced peptic ulcer disease, cramping, and diarrhea. Disodium cromoglycate stabilizes mast cell membranes, decreases m ediator release, and seems to be helpful in relieving cramping and diarrhea in some patients, but its use is controversial. Besides these extremely ag gravating symptoms, which can make life miserable for mastocytosis patients , serious problems such as life-threatening anaphylaxis may be associated w ith the release of mast cell mediators. Adrenaline and full supportive care may be necessary for anaphylaxis or vascular collapse induced by massive m ast cell degranulation. Furthermore, although the contribution of mast cell s and their mediators to the pathogenesis of the myelofibrotic and myelodys plastic bone marrow disease, severe anemia, and hematologic malignancy asso ciated with mastocytosis has not been determined, it is possible that the m ast cells directly contribute to these life-threatening conditions. Obvious ly, it would be preferable to treat mastocytosis by decreasing or eliminati ng the number of neoplastic mast cells. Several forms of therapy have been used to decrease mast cell numbers temporarily, but these therapies are ass ociated with significant adverse side effects. Psoralen-ultraviolet A thera py (PUVA) can decrease the number of cutaneous mast cells and suppress prur itus. Psoralen-ultraviolet A therapy may also have cosmetic benefits for pa tients with cutaneous mastocytosis, but its long-term use is associated wit h an increased risk of skin cancer, whereas its therapeutic benefits are on ly temporary. Likewise, topical or systemic corticosteroids may transiently decrease the mast cell burden and provide symptomatic relief, but they are associated with long-term cutaneous atrophy, adrenocortical suppression, o steoporosis, and aseptic necrosis of the femoral head, among other side eff ects. None of these therapies is directed against a specific cause of masto cytosis.