Karyotype complements the International Prognostic Scoring System for primary myelofibrosis

Hussein, Kebede; Huang, Jinsheng; Lasho, Terra L.; Pardanani, Animesh; Mesa, Ruben A.; Williamson, Cynthia M.; Ketterling, Rhett P.; Hanson, Curtis A.; Dyke, Daniel L. Van; Tefferi, Ayalew

doi:10.1111/j.1600-0609.2009.01216.x

Cited by 45 publications

(55 citation statements)

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“…JAK2V617F mutation analysis was performed using BM-derived cells, according to previously published methods [21,22]. Karyotype risk assignment was according to recent reports; normal karyotype or sole abnormalities of 13q2, 20q2, or 19 were considered ''favorable'' whereas all other abnormalities were listed as being ''unfavorable'' [16,18,23]. Transfusion-dependency was defined by the presence of transfusion history, regardless of amount, for a hemoglobin level of less than 8.5 g/dL.…”

Section: Methodsmentioning

confidence: 99%

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Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

et al. 2009

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The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty‐two patients (∼24%) required transfusions at diagnosis whereas 22 (∼9%) became transfusion‐dependent and 170 remained transfusion‐independent during the first year postdiagnosis; after a median follow‐up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS‐ and karyotype‐independent prognostic weight of transfusion status. Among IPSS intermediate‐1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate‐2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. Am. J. Hematol., 2010. © 2009 Wiley‐Liss, Inc.

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Section: Methodsmentioning

confidence: 99%

“…Karyotype constitutes another useful prognostic tool in PMF [16][17][18]. In this study, we examined the additional prognostic impact of transfusion need either at time of diagnosis or during the first year of diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

et al. 2009

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“…9 Del(20q) or del(13q) as well as normal karyotype are associated with a favorable prognosis, whereas most other cytogenetic aberrations render a negative prognostic impact. 10,11 Fewer than 100 cases of pediatric myelofibrosis have been reported worldwide and approximately half of published cases occurred in children younger than 3 years. These latter patients are more likely to have Down's syndrome, rickets or a familial (possibly autosomal recessive) form of myelofibrosis.…”

Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

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“…This result was not totally unexpected because of the well-established prognostic relevance of karyotype in myeloid malignancies. 39,40 We have in the past consistently shown the independent prognostic value of cytogenetic abnormalities, 31,[41][42][43][44] as well as thrombocytopenia 45,46 and red blood cell transfusion need, 47 in PMF. Similarly, there is no doubt that the current prognostic models will be further refined on the basis of new information regarding DIPSS-plus-independent genetic 48,49 and biological 50 risk factors, some of which also appear to be relevant in the context of myelodysplastic syndromes.…”

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confidence: 98%

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Tefferi

Lasho

Jimma

et al. 2012

Mayo Clinic Proceedings

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Objective: To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results. Patients and Methods: One thousand consecutive patients with primary myelofibrosis seen at Mayo Clinic between November 4, 1977, and September 1, 2011, were considered. The International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus were applied for risk stratification. Separate analyses were included for patients seen at time of referral (Nϭ1000), at initial diagnosis (Nϭ340), and within or after 1 year of diagnosis (Nϭ660). Results: To date, 592 deaths and 68 leukemic transformations have been documented. Parameters at initial diagnosis vs time of referral included median age (66 vs 65 years), male sex (61% vs 62%), red cell transfusion need (24% vs 38%), hemoglobin level less than 10 g/dL (38% vs 54%), platelet count less than 100 ϫ 10 9 /L (18% vs 26%), leukocyte count more than 25 ϫ 10 9 /L (13% vs 16%), marked splenomegaly (21% vs 31%), constitutional symptoms (29% vs 34%), and abnormal karyotype (31% vs 41%). Mutational frequencies were 61% for JAK2V617F, 8% for MPLW515, and 4% for IDH1/2. DIPSS-plus risk distributions at time of referral were 10% low, 15% intermediate-1, 37% intermediate-2, and 37% high. The corresponding median survivals were 17.5, 7.8, 3.6, and 1.8 years vs 20.0, 14.3, 5.3, and 1.7 years for patients younger than 60 years of age. Compared with both DIPSS and IPSS, DIPSS-plus showed better discrimination among risk groups. Five-year leukemic transformation rates were 6% and 21% in low-and high-risk patients, respectively. Conclusion: The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.

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Karyotype complements the International Prognostic Scoring System for primary myelofibrosis

Abstract: In PMF, specific cytogenetic abnormalities and not the mere presence of an abnormal karyotype provide important prognostic information that is not accounted for by the IPSS or other established risk factors.

Cited by 45 publications

References 25 publications

Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

Transfusion‐dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis—prognostic relevance is independent of IPSS or karyotype

How to manage children and young adults with myeloproliferative neoplasms

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

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