The ‘spent’phase of polycythaemia vera: hypersplenism in the absence of myelofibrosis

Abstract

A clinical phase (spent phase) in the course of polycythaemia vera (PV) cases is described as enlargement of the spleen in spite of treatment, frequent cytopenia of one or several lines, persistent red cell hypervolaemia with considerable increase of plasma volume, persistence of myeloid hyperplasia with no collagen myelofibrosis or osteomyelosclerosis, absence of hepatosplenic erythroblastic metaplasia, as shown by radio-iron kinetics and/or 111In-transferrin scintigraphy. The frequency of this phase was 5% in a study where it was not systematically sought, but it could in fact be greater. Its occurrence is not related to the clinical and biological parameters of PV. On the other hand, it is significantly more frequent and earlier in patients treated by phlebotomies than in those treated by myelosuppression (32P). In four of the 12 cases, this phase was rapidly followed by an acute leukaemia. In eight cases there was a 1-5 year interval before a myelofibrosis with splenic myeloid metaplasia. This evolution could at this stage be delayed by chemotherapy. The efficacy of splenectomy should be studied.

Polycythemia vera: myths, mechanisms, and management

“…123,125,128,129 With disease, changes occur in the plasma volume and red cell mass or in their distribution, particularly if there is splenomegaly 121,130-132 that will not be evident by hematocrit level determination alone. 109,[133][134][135][136] Indeed, the assumption that the hematocrit accurately reflects the red cell mass or, stated differently, that the red cell mass:plasma volume ratio is constant in health and disease or even for all parts of the circulation, is simply incorrect and nowhere more so than when erythrocytosis is present. 114,127,134,136 Remarkably, although it was established in 1921 123 and repeatedly confirmed 125,126,137,138 that only by independently measuring the red cell mass (currently with 51 chromium) and the plasma volume (with 125 I-albumin) could an accurate assessment of each as well as the total blood volume be obtained, there is still resistance to this standard of practice.…”

“…Initially and still employed to denote the progression of polycythemia vera to a state of bone marrow failure and possibly a prelude to leukemia 145,146 it has also been used to describe a phase of polycythemia vera with splenomegaly without either myelofibrosis or myeloid metaplasia in which erythrocytosis continues unabated with its extent masked by plasma volume expansion. 136 As indicated above, the former use of the term has never been authenticated in a scientifically acceptable fashion and the latter use, of course, is actually contradictory since in the type of patients described, bone marrow function was actually robust. 155,158 Furthermore, such patients have also been described by others as being in the "stationary phase" of the disease, 148 a designation that is equally improbable since no *The "expected" values were derived using the formulas from Pearson et al 139 These 4 examples illustrate that it is not possible to predict the red cell mass from the hematocrit alone and that in polycythemia vera a normal hematocrit value does not ensure that the red cell mass is normal.…”

The Optimal Management of Polycythaemia Vera

“…Importantly, iron deficiency in the absence of anaemia was not detrimental to aerobic performance in adults (Rector et al , 1982), did not cause an increase in blood viscosity (Pearson et al , 1981; Birgegard et al , 1984) and neither iron deficiency nor phlebotomy per se can increase the platelet count in a disorder in which bone marrow function is autonomous (Falconer, 1933; Stephens & Kaltreider, 1937; Kutti & Weinfeld, 1971; Messinezy et al , 1985). In patients with substantial splenomegaly, an elevated red cell mass can be masked by plasma volume expansion (Rothschild et al , 1954; Huber et al , 1964; Lamy et al , 1997); this can lead to under‐treatment, particularly if it is confused (Najean et al , 1984) with the so‐called ‘spent phase’ (Minot & Buckman, 1923) of the disorder.…”

Type III aminoterminal propeptide of procollagen in some haematological malignancies

“…It has been suggested that spent polycythaemia is a transitional stage during the course of PV, particularly in phlebotomized patients (15). Most of these patients develop myeloid metaplasia within 4 yr.…”