Darbepoetin Alpha For the Treatment of Anemia in Systemic Mastocytosis
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2019, Vol 13, Issue 5
Abstract
Human systemic mastocytosis (SM) is a rare disease caused by an abnormal mast cells accumulation in various tissues. The most aggressive forms have a rapid course and required treatments to reduce the neoplastic burden and to slacken the progression. Unfortunately, no therapy has been demonstrated efficacy, mostly in the treatment of aggressive systemic mastocytosis (ASM). Supportive treatments include growth factors, transfusions, steroids and anti-histaminic. No data have been reported so far concerning the use of darbepoetin alpha in this setting. Here, we describe a patient affected by ASM who experienced significant improvement of the hemoglobin level with darbepoetin (from 7.8 g/dl to 14.7 g/dl). Of note, a previous attempt with erythropoietin alpha did exert a transient response, which was lost before starting darbepoetin. We conclude that darbepoetin alpha might be considered for prospective evaluation within clinical trials in ASM patients with severe anemia. The Systemic mastocytosis (SM) is a rare disease that is characterized by over-proliferation and accumulation in organs and tissues of clonal mast cells (MCs). It usually occurs in adults involving skin, bone marrow, spleen, skeletal system, liver, or lymph nodes. The World Health Organization (WHO) classification divides the disease into cutaneous mastocytosis, systemic mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic mastocytosis is further divided into indolent systemic mastocytosis and advanced systemic mastocytosis variants, including aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL) [1,2]. Constitutional symptoms may be present, their intensity being quite variable, and directly related to tissue infiltration and to chemical mediators release by MCs [3,4]. Patients with ASM are marked by the presence of symptoms due to significant organopathy produced by MCs infiltration [1,2,5]. They include cytopenias, osteolysis (or osteoporosis) with pathologic fractures, hepatosplenomegaly with impaired liver function and ascites, and malabsorption. ASM can show a slowly progressing or a rapid clinical course, eventually shifting to MCL [1,2,5]. The molecular pathogenesis of SM has been largely studied in the last decade. In particular, gain-of-function point mutations of the activation loop of KIT have been found in the majority of cases [6-8]. These mutations result in ligand-independent, constitutive activation of KIT signaling, thus leading to uncontrolled MCs proliferation and resistance to apoptosis [6,7,9]. Of note, the most commonly observed KIT mutation involves the D816 residue and make the use of the tyrosine kinase inhibitor (TKI) imatinib mesylate useless, as the drug cannot bind this specific KIT mutant [10,11]. Similarly, second generation TKI such as dasatinib (Bristol- Mayer-Squibb) or nilotinib (Novartis Pharma), although probably more effective than imatinib, demonstrated a relative scarce activity [12-14]. Conversely, the third generation TKI midostaurin (Novartis Pharma) showed a significant activity in both ASM and MCL [15,16]. Alternative treatment options are represented by interferon alpha [17] steroids and chemotherapy [18]. Occasionally, successful usage of other agents has been reported [19,20]. Nonetheless, to date, irrespective of the clinical course, treatment of ASM and MCL is definitely challenging. Supportive treatments include growth factors, transfusions, steroids and anti-histaminic [21]. In particular, no data have been reported concerning the use of darbepoetin alpha (Amgen Switzerland AG) in SM patients presenting with anemia. Here, we describe a patient affected by ASM who experienced significant improvement of the hemoglobin (Hb) level with darbepoetin. Of note, a previous attempt with erythropoietin alpha (EPO) did only exert a transient response.
Authors and Affiliations
Pier Paolo Piccaluga, Michela Rondoni, Stefano Lazzi, Stefania Paolini, Giuseppe Visani
Keywords
Related Articles
- EP ID EP593789
- DOI 10.26717/BJSTR.2019.13.002462
- Views 124
- Downloads 0
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