Myelofibrosis with myeloid metaplasia in young indidviduals: disease characteristics, prognostic factors and identification of risk groups

Abstract

Summary. Myelofibrosis with myeloid metaplasia (MMM) isan uncommon disorder in young individuals, for whom haemopoietic stem cell transplantation offers the only possibility of cure. However, although the latter procedure is associated with significant morbidity and mortality, the clinical course of MMM is variable, with some patients surviving for less than a year and others showing an indolent course. Selection of young MMM patients for transplantation or other newer therapies is currently difficult since no prognostic data exists for this subgroup. In the present collaborative study a number of initial clinical and laboratory parameters have been evaluated for prognosis in 121 MMM patients aged 55 years or less. Median survival of the series was 128 months (95% CI 90-172). In the Cox proportional hazard regression model three initial variables were independently associated with shorter survival: Hb <10 g/dl (P < 0·0001), the presence of constitutional symptoms (fever, sweats, weight loss) (P ¼ 0·001), and circulating blasts у 1% (P ¼ 0·003). Based on the above three criteria, of the 116 patients with complete data, two groups were identified: a 'low-risk' group, characterized by 88 patients with up to one adverse prognostic factor, in whom MMM had an indolent course (median survival 176 months, 95% CI 130-188), and a 'high-risk' group, including 28 patients with two or three factors, who had a more aggressive disease (median survival 33 months, 95% CI 20-42). The above prognostic scoring system showed a high positive predictive value, sensitivity and specificity to predict survival in the series, and could be of help in making treatment decisions in young patients with MMM.

Myelofibrosis with Myeloid Metaplasia: New Developments in Pathogenesis and Treatment

“…In general, MMM is a disease that affects the older population with the median age at diagnosis being 60 years. However, in a small number of patients (10%), the disease is diagnosed before age 40 years (5). MMM has also been described in children where it seems to have a more benign course (6).…”

Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type

“…The distinction of different classes of disease presentation useful for therapeutic decisions is based on studies that have recognized prognostic factors, including age, Hb level, white-blood cell count, plt count, and these parameters have been incorporated into algorithms for risk assessment. 2,3,4 The current available treatment for PMF, including transfusions, androgens, thalidomide and myelosuppressive agents such as hydroxyurea, does not seem to modify the natural course of the disease. The recent identification of JAK2 mutations 5 in approximately 60% of patients with PMF has opened new areas of investigation, but targeted inhibitors are currently not yet available for clinical use.…”

“…Other risk-assessment scores for transplant eligibility have been introduced. They take into account the presence of constitutional symptoms and blasts (Cervantes score) 3 or plt count besides Hb and WBCs (Mayo score). 4 However, these scoring systems are constructed using parameters measured at diagnosis and are based on outcome of conventional treatment; thus, they are not necessarily applicable to the transplant setting.…”

Prognosis and survivorship in primary myelofibrosis

“…However, although a practical schema, it suffers from a number of limitations; firstly, the findings were based on a relatively small number of cases, indeed only 16 patients defined the high-risk group, secondly only a limited number of young patients were included in the study and lastly, the intermediate-and high-risk groups are not clearly separated. Cervantes et al [3] subsequently addressed the issue of the younger patient (defined as 55 years of age), but only two risk groups were proposed, based on hemoglobin level and the presence or absence of constitutional symptoms and circulating blasts.Recently, the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) has published the most robust prognostic scoring system to date-the socalled International Prognostic Scoring System (IPSS) [4]. This landmark paper was based on the evaluation of characteristics at presentation in 1054 patients from seven centers, diagnosed according to the World Health Organization (WHO) classification system.…”

“…However, although a practical schema, it suffers from a number of limitations; firstly, the findings were based on a relatively small number of cases, indeed only 16 patients defined the high-risk group, secondly only a limited number of young patients were included in the study and lastly, the intermediate-and high-risk groups are not clearly separated. Cervantes et al [3] subsequently addressed the issue of the younger patient (defined as 55 years of age), but only two risk groups were proposed, based on hemoglobin level and the presence or absence of constitutional symptoms and circulating blasts.…”