Expression of CD56 As A Prognostic Factor in Multiple Myeloma

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 23, 2007

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Presenter: Almeida, E. B.
Presenter's Affiliation: Department of Internal Medicine and Hematology/Hemotherapy Center, State University of Campinas UNICAMP, Brazil
Type of Session: Scientific

Background

  • Multiple myeloma (MM) is characterized by the absence of specific B-cell antigens, such as CD19
  • Aberrant expression of CD56 is the most common phenotypic abnormality in multiple myeloma (MM). However, its absence seems to be associated with a more aggressive form of the disease, including a higher incidence of chronic renal insufficiency and Bence-Jones protein levels.
  • The goal of the study was to compare the prognostic significance of CD56 expression with other known risk factors.

Materials and Methods

  • Design: Single institution, retrospective analysis
  • Patients:
    • 31 patients newly diagnosed with multiple myeloma
    • 13 males and 18 females
    • Median age: 60 years (46-74)
  • CD56 was quantitatively analyzed by flow cytometry (mean fluorescence intensity) on bone marrow cells.
  • Primary Endpoint:
    • Overall survival was analyzed using prognostic factors using both univariate and multivariate analysis with:
      • International Prognostic Score (IPI)
      • laboratory data
      • mean fluorescence intensity of surface cell markers
        • CD45
        • CD38
      • presence of deletion of chromosome 13q
  • Treatment:
    • The patients were treated according to the Brazilian Cooperative Myeloma Study

Results

  • Prognostic factors in study population:
    • IPI staging: 10 patients were stage I, 8 were stage II and 13 were stage III.
    • Expression of CD56: 68%
    • Deletion of 13q: 23%
  • Mean fluorescence intensity of CD56:
    • Directly correlated with the gamma peak (r=0.57)
    • Inversely correlated with proteinuria (r= –0.45) and IPI.
  •  No correlation between and the other markers determined by mean fluorescence intensity by flow cytometry.
  • Survival:
    • Significant variable in Univariate analysis:
      • Hemoglobin value
      • IPI
      • Mean fluorescence intensity of CD56
    • All three variables remained in the model in the multivariate analysis (Cox model) with IPI and hemoglobin as unfavorable variables and MFI CD56 as a favorable variable.
    • There was no association with survival of many serum markers, including beta-2-microglobulin, albumin, etc.
    • Only IPI Stage III appeared to have a worse survival (p=0.2)
    • Deletion of 13q had no impact on overall survival (p=0.92)

Author's Conclusions

  • Although there were few patients, the quantitative value of the expression of CD56 (mean fluorescence intensity) was a significant favorable parameter, more important than levels of beta2-microglobulin and cytogenetics.
  • The absence of CD56 could confer a worse prognosis by higher excretion of immunoglobulin light chain (Bence-Jones protein) leading to kidney damage, but this was not formally analyzed in this study.

Clinical/Scientific Implications

  • There has been much effort aimed at determining the disease burden and prognosis of patients with multiple myeloma using laboratory values. In fact, there are several staging systems in use, variable depending on factors such as hemoglobin, albumin, and beta-2-microglobulin.
  • The authors have evaluated the impact of quantitative CD56 measurement on survival in association with other commonly used prognostic markers. The number of patients was small, but they found that the absence of CD56 was a more important negative prognostic marker than beta-2-microglobulin or albumin.
  • Unfortunately, there were no analyses related to the renal toxicity or cause of death, so their interesting hypothesis that CD56 negativity is related to chronic renal insufficiency remains to be tested.



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