Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis: a study of 176 patients with prognostic implications

Cancer. 2013 May 15;119(10):1853-9. doi: 10.1002/cncr.27930. Epub 2013 Feb 19.

Abstract

Background: Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL.

Methods: Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0-3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well-recognized prognostic factors for CLL.

Results: The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32-86 years) and the 5-year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2-3) was associated with thrombocytopenia (platelet counts of < 100,000/mm(3) ) (P = .025), anemia (P = .018), elevated β2-microglobulin < 4000 μg/mL (P = .048), and the presence of 11q deletion (P = .0015).

Conclusions: There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / blood
  • Anemia / complications
  • Bone Marrow / chemistry
  • Bone Marrow / pathology*
  • Bone Marrow Examination
  • Chromosomes, Human, Pair 11
  • Coloring Agents
  • Female
  • Gene Deletion
  • Humans
  • Israel / epidemiology
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Odds Ratio
  • Platelet Count
  • Predictive Value of Tests
  • Primary Myelofibrosis / diagnosis*
  • Prognosis
  • Proportional Hazards Models
  • Reticulin*
  • Retrospective Studies
  • Severity of Illness Index
  • Silver Staining / methods
  • Thrombocytopenia / blood
  • Thrombocytopenia / complications
  • beta 2-Microglobulin / blood

Substances

  • Coloring Agents
  • Reticulin
  • beta 2-Microglobulin