Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET)

Barosi, Giovanni; Bron, Dominique; Brière, J; Cervantes, Francisco; Demory, Jean Loup; Dupriez, Brigitte; Gisslinger, Heinz; Grießhammer, Martin; Hasselbalch, Hans Carl; Kušec, Rajko; Bousse-Kerdilès, M. C. Le; Liberato, Nicola Lucio; Marchetti, Monia; Reilly, John T.; Thiele, Jürgen

doi:10.1182/blood-2005-04-1520

Cited by 74 publications

(61 citation statements)

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“…The present study included 40 MF patients who were uniformly treated at the same institution and in whom the response to treatment was assessed using modern criteria of response [15,16]. In a substantial proportion of patients, HU was effective in controlling the manifestations of MF, especially the hyperproliferative signs or symptoms, and, overall, 40% of the patients fulfilled the stringent IWG-MRT category of clinical improvement [16].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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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 ...

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Section: Discussionmentioning

confidence: 99%

“…The response was evaluated using the criteria of the European Myelofibrosis Network (EUMNET) [15] and those of the International Working Group for Myelofibrosis research and Treatment (IWG-MRT) [16]. The minimum time to assess the response was established as 3 months.…”

Section: Amongmentioning

confidence: 99%

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

et al. 2010

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“…In ET studies, complete response definition always included normalization of platelet count. Harmonization of response criteria to therapy in PV and ET, as made for PMF, 63,64 would be very useful, and several groups, especially the MPN working group of the European LeukemiaNet, are currently working on such consensus response criteria to be used in future studies.…”

Section: Results Of Clinical Trials Using Ifn-a In Mpnmentioning

confidence: 99%

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

2008

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Interferon (IFN) was the first cytokine discovered 50 years ago, with a wide range of biological properties, including immunomodulatory, proapoptotic and antiangiogenic activities, that rapidly raised interest in its therapeutic use in malignancies. IFN-receptor characterization was also pivotal in the discovery of the JAK/STAT signaling pathway. Among the large IFN family, mainly one of the type I IFN, IFN-a2, is used in therapy. Many clinical trials have shown remarkable efficacy of IFN-a in bcr-abl-negative myeloproliferative neoplasms (MPNs), especially polycythemia vera (PV), and essential thrombocythemia (ET). IFN-a induces about 80% of hematological responses in those diseases and is able to reduce splenomegaly, as well as relieve pruritus and other constitutional symptoms. Yet its use was limited by toxicity, leading to early treatment discontinuation in about 20% of the patients. However, its lack of leukemogenic potential and its possible use during pregnancy have already made IFN-a the drug of choice for younger MPN patients. In addition, several studies have shown a probably selective effect of IFN-a on PV and ET clones, as shown by cytogenetic remissions, reversions to polyclonal hematopoiesis, and more recently by induction of JAK2V617F complete molecular remissions in PV which may widen the indications of IFN-a in JAK2-mutated MPN.

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“…Fourteen patients in this study were pre-treated prior to analysis, the majority of whom were pre-treated with hydroxycarbamide. We analysed the response according to the European Myelofibrosis Network (EUMNET) criteria for response in myelofibrosis patients (Barosi et al, 2005). Notably, all of the patients were at least 18 years old.…”

Section: Peg-ifn-a-2a Therapy In Patients With Myelofibrosis a Study mentioning

confidence: 99%

PEG‐IFN‐α‐2a therapy in patients with myelofibrosis

Ianotto¹,

Kiladjian

Demory

et al. 2009

Br J Haematol

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showing a complete haematological and cytogenetic conversion and a ratio of 0AE0177% at quantitative RT-PCR. As regard to B-CLL, the peripheral blood flow-cytometric analysis revealed that the percentage of clonal lymphocytes had dropped from 80% to 8% (absolute count: from 8AE33 to 0AE33 · 10 9 /l), while FISH analysis showed trisomy 12 in 7% of the 300 nuclei examined. No peripheral lymphadenopathies were detected by physical examination. Abdominal ultrasound showed the reduction of splenomegaly (13 cm diameter) and the complete disappearance of the retroperitoneal lymphadenopathies. Our clinical observation, carried out on a rare case of B-CLL associated with CML, follows the few previously reported experiences on the successful use of dasatinib in B-CLL (Pitini et al, 2009). Although in vitro dasatinib appeared to be effective mainly in cases of unmutated B-CLL (Veldurthy et al, 2008) at concentrations difficult to attain in vivo (Amrein et al, 2008), our experience suggests that it can be active also in a IGHVmutated ZAP-70 negative case, at the usual dose. Obviously, the effectiveness of dasatinib in the treatment of patients affected by B-CLL needs to be exploited in prospective studies.

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Response criteria for myelofibrosis with myeloid metaplasia: results of an initiative of the European Myelofibrosis Network (EUMNET)

Abstract: The European Myelofibrosis Network (EUM-NET

Cited by 74 publications

References 20 publications

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

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

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

PEG‐IFN‐α‐2a therapy in patients with myelofibrosis

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