title: Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea.
abstract: Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.
authors.affiliation: a Department of Clinical Haematology , Austin Hospital, University of Melbourne , Heidelberg , VIC , Australia.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Douglas
authors.affiliation: b Department of Haematology , Guys and St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
authors.affiliation: c Wyong Hospital , Hamlyn Terrace , NSW , Australia.
authors.forename: Cecily
authors.initials: C
authors.lastname: Forsyth
authors.affiliation: b Department of Haematology , Guys and St Thomas' NHS Foundation Trust , London , UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: d Royal North Shore , Sydney , NSW , Australia.
authors.forename: William
authors.initials: W
authors.lastname: Stevenson
authors.affiliation: e Warrnambool Base Hospital , Warrnambool , VIC , Australia.
authors.forename: John
authors.initials: J
authors.lastname: Hounsell
authors.affiliation: f Royal Melbourne Hospital , Parkville , VIC , Australia.
authors.forename: Sumita
authors.initials: S
authors.lastname: Ratnasingam
authors.affiliation: f Royal Melbourne Hospital , Parkville , VIC , Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ritchie
authors.affiliation: g Flinders University and Medical Centre and SA Pathology , Adelaide , SA , Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.affiliation: a Department of Clinical Haematology , Austin Hospital, University of Melbourne , Heidelberg , VIC , Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009196:Myeloproliferative Disorders / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000209:etiology; D010677:Philadelphia Chromosome; D019233:Retreatment; D016019:Survival Analysis; D013927:Thrombosis / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan; D006918:Hydroxyurea
keywords: Philadelphia-negative myeloproliferative neoplasms; busulfan; hydroxyurea