Recombinant interferon-α in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response.
Recombinant interferon-α represents a well-established therapeutic option for the treatment of polycythemia vera and essential thrombocythemia. Recent studies also suggest a role for recombinant interferon-α in the treatment of 'early stage' primary myelofibrosis, but few studies have reported the bone marrow changes after clinically successful interferon therapy. The aim of the present study is to detail the histological responses to recombinant interferon-α in primary myelofibrosis and post-polycythemia vera/post-essential thrombocythemia myelofibrosis and to correlate these with clinical findings. We retrospectively studied 12 patients with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis, who had been treated with recombinant interferon-α. Six patients had received other prior cytoreductive therapies. Bone marrow biopsy was assessed for the following histological parameters: (i) cellularity; (ii) myeloid-to-erythroid ratio; (iii) megakaryocyte tight clusters; (iv) megakaryocyte and naked nuclei density; (v) megakaryocytic atypia; (vi) fibrosis; and (vii) the percentage of blasts. Clinical and laboratory data were included: (i) constitutional symptoms; (ii) splenomegaly, if present; and (iii) complete cell blood count. The clinical response to therapy was evaluated using the International Working Group for Myelofibrosis Research and Treatment/European LeukemiaNet response criteria. The Dynamic International Prognostic Scoring System (DIPSS) score was calculated before and after recombinant interferon-α administration. Successful interferon therapy for myelofibrosis was associated with a significant reduction of marrow fibrosis, cellularity, megakaryocyte density and naked nuclei density. The presence of JAK2(V617F) mutation correlated with improved DIPSS score. JAK2(V617F)-negative cases showed worsening of such score or evolution to acute myeloid leukemia. Cytogenetic analysis documented a normal karyotype in all cases. In conclusion, successful clinical response to interferon-α correlates well with an improvement of bone marrow morphology. The prognostic effect of such therapy may be influenced by the JAK2 mutational status. Additional studies are needed to confirm these preliminary data.
Hematopathology Division, Department of Pathology and Laboratory Medicine, New York Presbyterian/Weill Cornell Medical College, New York, NY, USA.|Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Marco
http://orcid.org/0000-0003-4006-7317
M
Pizzi
Richard T. Silver Myeloproliferative Neoplasms Center, Department of Hemathology/Oncology, Weill Cornell Medical College, New York, NY, USA.
Richard T
RT
Silver
Richard T. Silver Myeloproliferative Neoplasms Center, Department of Hemathology/Oncology, Weill Cornell Medical College, New York, NY, USA.
Ariella
A
Barel
Hematopathology Division, Department of Pathology and Laboratory Medicine, New York Presbyterian/Weill Cornell Medical College, New York, NY, USA.
Attilio
A
Orazi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D055815:Young Adult
D016898:Interferon-alpha; D011994:Recombinant Proteins; C507924:JAK2 protein, human; D053614:Janus Kinase 2