title: Pegylated interferon for the treatment of early myelofibrosis: correlation of serial laboratory studies with response to therapy.
abstract: Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2-63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy.
authors.affiliation: Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MC9172, Los Angeles, CA, 90033, USA. cmoneill@usc.edu.
authors.forename: Caitlin
authors.initials: C
authors.lastname: O'Neill
authors.affiliation: Hematopathology Section, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Imran
authors.initials: I
authors.lastname: Siddiqi
authors.affiliation: Hematopathology Section, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Russell K
authors.initials: RK
authors.lastname: Brynes
authors.affiliation: Hematopathology Section, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Vergara-Lluri
authors.affiliation: Hematopathology Section, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Moschiano
authors.affiliation: Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MC9172, Los Angeles, CA, 90033, USA.
authors.forename: Casey
authors.initials: C
authors.lastname: O'Connell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D001856:Bone Marrow Examination; D018450:Disease Progression; D004341:Drug Evaluation; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008875:Middle Aged; D011087:Polycythemia Vera / Q000150:complications / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D055728:Primary Myelofibrosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012155:Reticulin / Q000648:ultrastructure; D016037:Single-Blind Method; D013163:Splenomegaly / Q000209:etiology / Q000517:prevention & control; D013920:Thrombocythemia, Essential / Q000150:complications / Q000235:genetics / Q000473:pathology
chemical_list: D015415:Biomarkers; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012155:Reticulin; D011092:Polyethylene Glycols; D007770:L-Lactate Dehydrogenase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: Laboratory findings; Myeloproliferative neoplasms; Pegylated interferon