title: Fractal characteristics of May-Grünwald-Giemsa stained chromatin are independent prognostic factors for survival in multiple myeloma.
abstract: BACKGROUND
  The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma.
  
  
  METHODS
  We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R(2) values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation.
  
  
  RESULTS
  Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R(2), and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study.
  
  
  CONCLUSIONS
  Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with multiple myeloma.
authors.affiliation: Department of Pathology, University of Campinas, Campinas, Brazil.
authors.forename: Daniela P
authors.initials: DP
authors.lastname: Ferro
authors.forename: Monica A
authors.initials: MA
authors.lastname: Falconi
authors.forename: Randall L
authors.initials: RL
authors.lastname: Adam
authors.forename: Manoela M
authors.initials: MM
authors.lastname: Ortega
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Lima
authors.forename: Carmino A
authors.initials: CA
authors.lastname: de Souza
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Konradin
authors.initials: K
authors.lastname: Metze
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation; D002843:Chromatin / Q000378:metabolism*; D004801:Eosine Yellowish-(YS); D005260:Female; D017709:Fractals; D006801:Humans; D008297:Male; D008751:Methylene Blue; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D013534:Survival
chemical_list: D002843:Chromatin; C043260:May-Grunwald Giemsa; D008751:Methylene Blue; D004801:Eosine Yellowish-(YS)