Bone Marrow Fibrosis of Adult Patients in Mexico
Description
The role of bone marrow (BM) fibrosis on outcomes of children with acute lymphoblastic leukemia (ALL) has been described with inconsistent results, while in adults there is no information regarding its significance. Considering the poor outcomes of adult patients with ALL, the aim of this study was to describe the prognostic impact of BM fibrosis in this group of patients. We included 88 biopsies of 44 adult patients. Masson trichrome stain and grading of fibrosis by Bauermeister scale and volume of reticulin fibers was performed. Patients were classified in 3 groups: without fibrosis at diagnosis (Group 1), with fibrosis and reduction of volume of reticulin fibers <50% (2) or ≥50% (3). At diagnosis 66% (n=29) had significant fibrosis with a median volume of reticulin fibers of 15.3% at diagnosis and 9.5% post-induction. Fibrosis at diagnosis had no impact over the outcomes, however, reduction of ≥50% of the volume of reticulin fibers after induction was associated with less induction failure (10% vs. 46%, p=.018), longer relapse free survival (12.1 months vs. 10.5 months, p=.037) and longer overall survival (28.3 months vs. 13.1 months, p=.028). To our knowledge, this is the first study to demonstrate that significant bone marrow fibrosis at diagnosis and its subsequent reduction is related to a better clinical outcome in adult patients with ALL.
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From February 2011 to February 2016, we retrospectively collected demographic information, clinical data, and outcomes from clinical records of patients. We included patients aged ≥ 18 years diagnosed with ALL, treated and followed at our institution, with available and good-quality BM biopsies on diagnosis and post-induction, and who had no previous cancer or disease known to cause BM fibrosis. Pathology material was discarded when samples were crushed, had extensive necrosis, and/or the evaluation area was less than three marrow spaces. Hematoxylin-eosin and Masson trichrome stains were performed. Fibrosis was described using both modified Bauermeister scale as described by Bain et al. and volume of reticulin fibers adapted from Nóren-Nyström et.al. Modified Bauermeister scale included four groups: group 0 with no reticulin fibers demonstrable, group 1 with occasional fine individual fibers, group 2 with diffuse fiber network of fine fibers without coarse fibers, group 3 with diffuse fiber network with scattered thick coarse fibers, and group 4 with diffuse coarse fiber network. The volume of reticulin fibers for each sample was estimated using a 63-point graticule representing 25 microns2 at x40 magnification in 10 randomly selected fields within the marrow area and finally expressed as the average of this 10 selected fields per sample. The volume was determined by the percentage of the area occupied by graticule-crossing points or hits overlaying reticulin fibers versus hits over reference space. A Lumera microscope camera and Infinity Analyze software version 6.4.1 was used. The data was analyzed using SPSS 20.0. Data is in Spanish