The disorder formerly referred to by various names but which we will, as a result of the present work, call myelofibrosis with myeloid metaplasia (MMM), belongs to the clonal proliferations of haemopoiesis categorized among the spectrum of chronic myeloproliferative disorders (CMD). The need to unequivocally distinguish individual clinical entities among CMD led to ad hoc committees which developed diagnostic criteria, and the literature now reports parameters designed to identify certain ones such as chronic myeloid leukaemia (CML) (Bennett et al, 1994), polycythaemia vera (PV) (Berlin, 1975) and essential thrombocythaemia (ET) (Murphy et al, 1986). Criteria for the diagnosis of MMM were first proposed by Laszlo (1975) of the Polycythemia Vera Study Group (PVSG). The features agreed upon included fibrosis involving more than one-third the sectional area of a bone marrow biopsy, splenomegaly, leucoerythroblastic blood reaction, the absence of an increased red blood cell mass and the absence of the Philadelphia chromosome. However, over the last 20 years a wide range of clinical and pathologic phenotypes of the disease (Bentley et al, 1977; Barosi et al, 1983, 1991; Polino et al, 1986) and mixed or transitional CMD with features resembling MMM (Krauss, 1966; Pettit et al, 1976) have been reported. Moreover, among the disorders categorized under the heading of myelodysplastic syndromes (MDS) (Bennett et al, 1982; Kouides & Bennet, 1996), the possibility of true myeloproliferative characteristics as in chronic myelomonocytic leukaemia (CMMoL) (Fenaux et al, 1987; Storniolo et al, 1990; Bennett et al, 1994; Greenberg et al, 1997; Niemeyer et al, 1997), presentation with bone marrow fibrosis (Pagliuca et al, 1989; Verhoef et al, 1991; Maschek et al, 1992; Krishnan & Seldon, 1996) and mixed myelodysplastic and myeloproliferative features (Neuwirtova et al, 1996) make the distinction between MMM difficult in some cases. These reasons led most of the published MMM series to report patient populations which were less strictly defined than that required by the originally proposed criteria. In particular, the parameters of normal or decreased red cell mass (Barosi et al, 1988; Visani et al, 1990; Dupriez et al, 1996), and the presence of splenomegaly at diagnosis of the disease (Cheng, 1979; Rupoli et al, 1994; Barosi et al, 1998), do not always seem to have been met in all patients. Moreover, others did not consider bone marrow fibrosis to be a necessary diagnostic criterion in early hypercellular stages when haemopoiesis is characterized by an abnormal cytologic appearance of megakaryocytes (Georgii et al, 1990; Thiele et al, 1996) and the term ‘chronic megakaryocytic-granulocytic myelosis’ was coined to describe the early nonfibrotic stage of myelofibrosis (Georgii et al, 1990).
The lack of accepted standardization of criteria for distinguishing among the spectrum of similar forms may lead to nonhomogenous inclusion of patients in clinical trials with the risk of reporting bias, ambiguous interpretation of results, and the inability to compare therapies. Perceiving the need for rigorous, consistent and feasible criteria for the diagnosis of MMM, we undertook this project. Our purpose was to identify a core set of criteria and to develop a definition of MMM that would aid in the classification of individual patients as well as be applicable to future clinical studies. We envisioned that the definition of MMM might also be useful for physicians assessing patients in routine practice.