Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes

Abstract

Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration ("diffuse," "cluster," and "large") were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was "diffuse" in 18, "cluster" in 48, and "large" in 40 cases. RAEB-t patients accounted for about half of the "large" cases, and none had a "diffuse" pattern (p < 0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by "cluster" blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of "large" cases (p< 0.001) and in none of the "cluster" cases with severe BM fibrosis (p < 0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with "cluster" BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.

Bone marrow fibrosis in patients with primary myelodysplastic syndromes has prognostic value using current therapies and new risk stratification systems

“…20 The results we present here confirm the prognostic importance of bone marrow fibrosis in patients with primary myelodysplastic syndromes. 1,[4][5][6][7] This adverse feature not only affected patients treated with non-transplant modalities but also patients who received hematopoietic stem cell transplant. The latter was in keeping with the study reported by Kroger et al 19 that severe bone marrow fibrosis was an independent risk affecting transplant outcome in patients with myelodysplastic syndromes.…”

“…3 In recent years, bone marrow fibrosis has been increasingly recognized as an adverse feature in patients with myelodysplastic syndromes, which correlates with increased risk of early bone marrow failure, transformation to acute myeloid leukemia, and an inferior patient outcome. [4][5][6][7][8] Some of these studies, however, preceded the European consensus criteria established for grading bone marrow fibrosis 9 and/or prior to the recent advent of therapeutic agents for myelodysplastic syndromes, such as lenolidomide and hypomethylating agents. In a study conducted by Della Porta et al, 5 patients with myelodysplastic syndromes who received hematopoietic stem cell transplantation or chemotherapy were censored at the time of therapeutic procedure.…”

Comparison of hypoplastic myelodysplastic syndrome (MDS) with normo-/hypercellular MDS by International Prognostic Scoring System, cytogenetic and genetic studies

“…2,17,[28][29][30][31][32][33][34][35][36] This could be explained by the exclusion of chronic myelomonocytic leukemia in our series. Chronic myelomonocytic leukemia has been reclassified into the category of myelodysplastic/myeloproliferative diseases in the new WHO (World Health Organization) classification in 2001.…”

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

“…Founding the evaluations on patients whose bone marrow had been planned up-front to be both aspirated and biopsied for initial diagnosis of an unclear cytopenia, it is unlikely that full-blown MF affects more than 30% of patients with primary MDS, an observation which is in agreement with earlier results from other authors. 12,13 In a minority of patients, MF may be not detectable on the day of diagnosis, but may emerge during the further course of disease. The majority of these patients show FFI in a previous bone marrow biopsy, indicating that fibrosis emerges focally within bone marrow rather than diffusely, an observation similar to the data recently reported from patients with chronic myeloid leukemia.…”

“…8 However, occurrence of fibrosis is not mentioned in the disorders summarized in the section 'Myelodysplastic Syndromes', 8 and up to now, there have been no data on the frequency of MF within this new classification system. 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).…”