title: Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine.
abstract: 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.
authors.affiliation: Divisions of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Lim
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Butterfield
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D017338:Cladribine / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D034721:Mastocytosis, Systemic / Q000145:classification / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D010879:Piperazines / Q000627:therapeutic use*; D017354:Point Mutation; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D017338:Cladribine; D000068877:Imatinib Mesylate; D049308:Dioxygenases; C541081:TET2 protein, human; D019009:Proto-Oncogene Proteins c-kit; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D011241:Prednisone; D006918:Hydroxyurea