Myelofibrosis in Primary Myelodysplastic Syndromes: Clinical and Biological Significance

Abstract

In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.

Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes

“…Even when including patients with FFI, the high frequencies of MF exceeding 50% of patients with primary MDS as reported by some authors 17,19 could not be supported by our observations. Considering the strong dependence of the diagnosis of MF on the technical preparation of BMBs 39 and on the approach used to prove MF, 23 the diversity in the reported frequencies appears to reflect technical problems or problems of selection rather than a biological difference.…”

“…Previous publications reporting on the occurrence of MF in a relevant proportion of patients with an MDS are more than 10 years old, [12][13][14][15][16][17] they are based on rather small numbers of patients, 15,16,18 or they differ in their results on the frequency and significance of MF. 12,13,16,19 Therefore, we performed a retrospective study on the occurrence and significance of MF, relating the results to the WHO classification of MDS and the International Prognostic Scoring System (IPSS). 20 …”

Allogeneic stem cell transplantation for myelodysplastic syndromes with bone marrow fibrosis

“…The prognostic impact of bone marrow fibrosis in MDS patients has come into focus and several studies have confirmed a negative impact of fibrosis on survival [3][4][5][6][7] with some authors suggesting that MDS with fibrosis could be considered as a distinct entity. [9][10][11] Although bone marrow fibrosis is not included in the current prognostic risk scores such as the Allogeneic SCT for MDS with bone marrow fibrosis haematologica | 2011; 96 (2) 295 483 206 159 135 108 75 75 199 78 56 56 35 33 23 39 14 10 10 10 10 3 721 298 225 201 153 118 101 721 223 154 84 58 58 483 161 95 56 33 33 199 55 55 24 24 24 39 7 4 4 …”

Hypocellular myelodysplastic syndrome with myelofibrosis in acute myeloid leukemia transformation: A case report

“…It is the myelofibrosis that makes the treatment more difficult due to the ease of relapse and transformation into AML. Patients with relapsed and transformed disease experience multi-drug resistance, a poor curative effect and high mortality rates (11). The synergy between the drugs in FLAG chemotherapy enhance cytotoxicity, therefore, it is now widely used in refractory and relapsed acute leukemia, and high-risk MDS treatment (12).…”