Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients

Abstract

Hydroxyurea (HU) is frequently given as treatment for myelofibrosis (MF), but data on its efficacy and tolerability are scarce. The results of HU therapy were evaluated in 40 patients with hyperproliferative manifestations of primary (n= 32), post-polycythemia vera (n= 6) or post-essential thrombocythemia (n= 2) myelofibrosis. Median interval between diagnosis and HU start was 6.2 months (range: 0-141.7). Reasons for treatment were: constitutional symptoms (55%), symptomatic splenomegaly (45%), thrombocytosis (40%), leukocytosis (28%), pruritus (10%), and bone pain (8%). The starting dose was 500 mg/day, subsequently adjusted to the individual efficacy and tolerability.Response was: bone pain 100%, constitutional symptoms 82%, pruritus 50%, splenomegaly 40%, and anemia 12.5%. According to the International Working Group for Myelofibrosis Research and Treatment criteria, clinical improvement was achieved in 16 patients (40%). Median duration of response was 13.2 months (range: 3-126.2). Worsening of the anemia or appearance of pancytopenia were observed in 18 patients, requiring administration of erythropoietin-stimulating agents (n=17) and/or danazol (n=9). Oral or leg ulcers appeared in 5 patients and one had gastrointestinal symptoms. HU is an effective and generally well-tolerated therapy for the hyperproliferative manifestations of MF. The accentuation of the anemia often induced by HU is usually manageable with concomitant treatment.Response to Reviewers: Answers to the comments by reviewer 1:1. Retrospective design of the study. As already stated in the Introduction and in the Discussion, although there is limited bibliographic support for the use of hydroxyurea (HU) in MF, in clinical practice, this drug has been considered for many years (and still is) as the standard therapy for the hyperproliferative manifestations of this disease. Actually, until the recent development of the JAK2 inhibitors, no real alternative therapy to HU was available for comparison. As a result, for the time being, a retrospective study is the only possibility to assess the efficacy and tolerability of HU in MF.Having said this, it must be remarked that the data from the present study have been generated in a single institution, in which the drug was used following uniform rules for the starting dose, the dose adjustments and the use of adjuvant drugs for the treatment of the associated anemia. Moreover, more than 80% of the patients in the study were treated by the same physician, with long-lasting and specific dedication to MF.2. Selection of the patients. As stated in the Patients and Methods, the 40 patients included in the study were the only ones receiving HU among the 157 with MF followed in our institution during the study period. As also stated in the same section, HU was given to these 40 patients exclusively as a treatment for the hyperproliferative manifestations of MF (i.e., constitutional symptoms, symptomatic splenomegaly, pruritus, bone pain, leukocytosis, and thrombocytosis). This means that a patient ...

Guideline for the diagnosis and management of myelofibrosis

“…An early study suggested a response rate of approximately 45% (Löfvenberg & Wahlin, 1988), although the degree of splenic reduction was not detailed. Similar findings were reported in a recent study of 18 MPN patients with symptomatic splenomegaly (Martinez-Trillos et al, 2010). Overall, complete responses are rare and doses of more than 1·5 g/d may be required to achieve clinical effect.…”

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

“…2). First-line drugs of choice in such patients are hydroxyurea for symptomatic splenomegaly [125], androgens preparations [126], prednisone [126], danazol [127], thalidomide 6 prednisone [128][129][130] or lenalidomide 6 prednisone [131,132] for symptomatic anemia, splenectomy (or splenic radiotherapy for nonsurgical candidates) for splenomegaly that is resistant to conventional drug therapy [133], involved field radiotherapy for nonhepatosplenic EMH might and ruxolitinib for severe constitutional symptoms that are resistant to hydroxyurea therapy [133].…”

Management of Myelofibrosis

“…37 Indeed, results from the randomized COMFORT-II study indicated that none of the patients in the best-available therapy arm presented measurable improvements in symptoms, as measured by the EORTC QLQ-C30 or FACT-Lym scores. 34 Low-dose prednisone may sometimes produce a feeling of well-being, but the effect is usually modest and transient.…”