Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine

Divisions of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
American Journal of Hematology (Impact Factor: 3.8). 12/2009; 84(12):790-4. DOI: 10.1002/ajh.21561
Source: PubMed


Cytoreductive therapy in systemic mastocytosis (SM) includes several drugs whose individual merit has not been well characterized. We retrospectively studied 108 Mayo Clinic patients who met the 2008 WHO diagnostic criteria for SM and received at least one cytoreductive drug. The numbers of patients who were evaluable for response to treatment with interferon-alpha with or without prednisone (IFN-alpha), hydroxyurea (HU), imatinib mesylate (IM) or 2-chlorodeoxyadenosine (2-CdA) were 40, 26, 22, and 22, respectively. The corresponding overall (major) response rates, according to recently published consensus criteria, were 53% (18%), 19% (0%), 18% (9%), and 55% (37%). The respective overall response rates in indolent SM, aggressive SM and SM associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD) were 60%, 60%, 45% for IFN-alpha, 0, 0, 21% for HU, 14%, 50%, 9% for IM and 56%, 50%, 55% for 2-CdA. The absence of mast cell mediator release symptoms in IFN-alpha-treated patients and presence of circulating immature myeloid cells in 2-CdA-treated patients predicted inferior response. TET2 mutational status did not influence treatment response. Although the major response rates with these four cytoreductive agents were still suboptimal and HU was mainly used in patients with SM-AHNMD, the current study favors 2-CdA or IFN-alpha as first-line current therapy in SM and identifies patients who are likely to respond to such therapy.

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Available from: Ken-Hong Lim, Dec 17, 2014
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    • "The largest series published by Lim et al. in 2009 has analysed 30 patients treated by 2-CdA with an ORR ranging from 50 to 56 % according to M subtypes 3 . However, few patients with indolent systemic mastocytosis (ISM), smouldering systemic mastocytosis (SSM) or "
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    ABSTRACT: Mastocytosis (M) is a clonal myeloid disabling disorder for which no curative therapy is currently available. Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a synthetic purine analogue cytoreductive treatment, which efficacy is mostly reported in advanced M. Here we report, with a long term follow-up period (over 10 years) efficacy and safety in 68 adult patients with M (36 pts (53%) had indolent M and 32 (47%) had advanced M) treated by 2-CdA (0.14 mg/kg in infusion or subcutaneously, days 1-5; repeated at 4-12 weeks until 1 to 9 courses). Median 2-CdA courses number was 3.7 (1 to 9). The overall response rate was 72% (Complete R/Major /Partial R: 0%/47%/25%) and according to indolent/advanced M was 92% (Major/Partial R: 56%/36%) and 50% (Major/Partial R: 37.5%/12.5%), respectively. Clinical improvement was observed for 10/11mediator release and 6/7 mast cell infiltration-related symptoms including urticaria pigmentosa, and organomegaly (P<.02). Serum tryptase levels decreased (P= .01). Median durations of response were 3.71 (0.1-8), 2.47 (0.5-8.6) years for indolent and aggressive M, respectively. The most frequent grade 3/4 toxicities were lymphopenia (82%), neutropenia (47%), and opportunistic infections (13%). 2-CdA appears to provide a significant efficacy with some toxicity in various M subtypes, mostly in indolent M, refractory to multiple symptomatic therapies. Copyright © 2015 American Society of Hematology.
    Blood 05/2015; 126(8). DOI:10.1182/blood-2014-12-614743 · 10.45 Impact Factor
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    • "HU has been used in the treatment of mastocytosis, too, and has been associated with reductions in MC load and symptoms [17] as well as reductions in symptoms without clear reduction in MC load (e.g., malaise and pruritus [18]; progressive decrease in clinical symptoms and the need for intensive antimediator therapy [19]; weight loss, severe night sweats, abdominal pain, and pruritus [20]; facial flushing and bone pain [21]; and pruritus, flushing, ascites, and hepatosplenomegaly [22]). These reports suggest HU might be able to modulate MC mediator expression in some patients independent of its anti-proliferative effects. "
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    ABSTRACT: Mast cell activation syndrome (MCAS) is a relatively recently recognized cause of chronic multisystem polymorbidity of a generally inflammatory theme. Patients with MCAS often report migratory soft tissue and/or bone pain which frequently responds poorly to typical (narcotic and non-narcotic) analgesics as well as atypical analgesics such as antidepressants and anticonvulsants. Hydroxyurea (HU) is an oral ribonucleotide reductase inhibitor commonly used in the treatment of chronic myeloproliferative neoplasms and sickle cell anemia. HU has been used to treat systemic mastocytosis, sometimes effecting improvement in MC activation symptoms but not tumor burden, suggesting potential utility of the drug in MCAS, too. Reported here are five cases of successful use of relatively low-dose HU in MCAS to reduce symptoms including previously refractory soft tissue and/or bone pain. HU may be useful in treating mediator symptoms in MCAS, but further study is needed to define optimal dosing strategies and patient subpopulations most likely to benefit.
    10/2013; 2(1). DOI:10.1186/2162-3619-2-28
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