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Fathi, Amir

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Fathi

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Amir

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Fathi, Amir

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2015 - 20172

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Author's Publications: search.filters.isAuthorOfPublication.94a0d81a-6554-45fb-a88e-62a7bb7daad7

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    Acute myeloid leukemia in a patient with constitutional 47,XXY karyotype
    (Elsevier, 2015) Jalbut, Marla M.; Sohani, Aliyah R.; Cin, Paola Dal; Hasserjian, Robert; Moran, Jenna A.; Brunner, Andrew; Fathi, Amir
    Klinefelter syndrome (KS), a 47,XXY chromosomal abnormality, has been shown to be associated with a number of malignancies, but has not been linked to acute leukemias to date. We present a case of a 54-year-old male diagnosed with acute myeloid leukemia (AML) with monocytic differentiation, whose cytogenetic and subsequent FISH analyses revealed a constitutional 47,XXY karyotype. We also review and discuss relevant prior literature.
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    Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia
    (Ferrata Storti Foundation, 2017) Fathi, Amir; Wander, Seth; Blonquist, Traci M.; Brunner, Andrew; Amrein, Philip; Supko, Jeffrey; Hermance, Nicole M.; Manning, Amity L.; Sadrzadeh, Hossein; Ballen, Karen K.; Attar, Eyal C.; Graubert, Timothy; Hobbs, Gabriela; Joseph, Christelle; Perry, Ashley M.; Burke, Meghan; Silver, Regina; Foster, Julia; Bergeron, Meghan; Ramos, Aura Y.; Som, Tina T.; Fishman, Kaitlyn M.; McGregor, Kristin L.; Connolly, Christine; Neuberg, Donna; Chen, Yi-Bin
    Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring “5+2” reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68–96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33–81%) and 42% (90% CI 17–65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. (clinicaltrials.gov Identifier:01779843).