The impact of peripheral blood values and bone marrow findings on prognosis for patients with essential thrombocythemia and polycythemia vera

Abstract

The Philadelphia chromosome-negative (Ph-) chronic myeloproliferative neoplasms include the three well-known clinical entities polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Over time, patients with ET and PV may develop myelofibrosis (MF), and all three entities carry a risk of transformation into acute myeloid leukemia (AML). In a population-based survey during 1983-1999, we studied a total of 358 patients who were diagnosed with ET and PV in the city of Gothenburg, Sweden. At the time of diagnosis, evaluable bone marrow biopsy material was available from 280 of these patients. The current work was aimed at investigating the impact of peripheral blood counts, spleen size, and bone marrow biopsy findings at diagnosis on long-term survival and the risk of development of AML or MF in this well-defined unselected population. The variables evaluated were venous blood hemoglobin concentration, packed cell volume, white blood cell count, platelet count, and splenic enlargement; as to bone marrow biopsies, interest was focused on reticulin content, focal or generalized collagen formation, bone marrow cellularity, and megakaryocyte profile number. Over the median observation time of 15 yr, the patients with ET did not demonstrate any significant difference as to survival compared to the normal Swedish population (hazard ratio, 1.23; 95% confidence interval, 0.97-1.51; p= 0.089). The patients with PV, on the other hand, had a significantly shorter survival compared to general population (hazard ratio, 1.66; 95% confidence interval, 1.38-1.99; p< 0.001). A lower hemoglobin concentration at diagnosis of ET predicted poorer survival (p =0.0281), whereas patients with PV with splenic enlargement at diagnosis had a shorter survival (p =0.037). In the patients with ET, the risk of transformation to either MF or AML was significantly associated with low hemoglobin concentration and high white cell count at diagnosis (p =0.0037 and 0.0306, respectively). An increased reticulin content and hypercellularity in the bone marrow at diagnosis were also independent risk factors (p =0.0359 and 0.0103, respectively). The risk of transformation in patients with PV was significantly associated with splenic enlargement and increase in bone marrow reticulin content (p =0.0028 and 0.0164, respectively).

Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies

“…However, BMF grade was not associated with worse overall survival. 52 These results were replicated in another study by Campbell et al in which 311 patients with essential thrombocythemia were included. Again, increased reticulin BMF grade at diagnosis was not significantly associated with poorer overall survival.…”

Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome

“…1,4,5 In a recently published study, an even more increased incidence was found in 143 PVSG-defined PV patients, including slight reticulin fibrosis in approximately 20% and moderate to marked fibrosis in 51% of cases. 6 In contrast to these relatively high frequencies at presentation, other larger series reported lower ranges between 10% and 20%, with a significant prevalence of a minor fiber grade. 2,[7][8][9] In this context, scant knowledge is available regarding the precise relationship of initial BM fibrosis and clinical activity of PV.…”

“…2,[7][8][9] In this context, scant knowledge is available regarding the precise relationship of initial BM fibrosis and clinical activity of PV. 1,6 To date, it has not been clear whether a minor increase in reticulin fibrosis indicates a later stage of disease or a more aggressive course with a more rapid evolution into the so-called spent phase (post-PV myelofibrosis). In the 25 patients of the PVSG study with marked to moderate fibrosis, follow-up examinations failed to reveal a predictive value, and sequential biopsies showed that myelofibrosis may be present for a long time before onset of spent-phase PV.…”

“…1 On the other hand, although no relationships between BM fibrosis and bleeding or thrombosis could be ascertained, a higher reticulin fibrosis grade was regarded as an independent risk factor for transformation into overt myelofibrosis (post-PV myelofibrosis) or acute leukemia. 6 In the present study, we examine the incidence and prognostic role of minor reticulin fibrosis at presentation of PV, diagnosed according to the World Health Organization (WHO) criteria. 10 Our study population was derived from an international, multicenter PV database.…”

Genetic Markers of Hereditary Thrombophilia and Risk of Thrombotic Complications in Patients with Polycythemia Vera

“…В одном из них было показано, что снижение содержания ретикулина и низкая кле-точность костного мозга связаны с артериальными тромбозами (АТ), но не с венозными (ВТ) [17]. В про-тивоположность этому в ходе другого исследования было выявлено, что начальные признаки фиброза значимо коррелируют с низкой частотой массивных АТ и ВТ [18].…”