Originally published as JCO Early Release 10.1200/JCO.2009.23.8683 on July 6 2009

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Reply to R.S. Go

Department of Medicine, Mayo Clinic, Rochester, MN

To the Editor:

We thank Dr Go¹ for bringing up an important and interesting question in reference to our recent article²: Can a patient's albumin level affect the number of smudge cells found on a blood smear? We demonstrated that a high smudge-cell percentage was associated with a better prognosis in chronic lymphocytic leukemia (CLL). As Dr Go points out, excess protein is added at some centers during slide preparation to prevent/reduce smudge-cell formation created by shear forces. Since a low albumin level has been shown to be associated with an adverse prognosis in CLL,^3–5 the correction of smudge-cell percentage for albumin level could refine the prognostic significance of smudge cells if indeed these variables are associated.

To explore this aspect, we investigated the correlation between albumin level and the percentage of smudge cells. Albumin level was available for 98 (91%) of 108 CLL patients in our original cohort. The median albumin level was 4.2 g/dL (range, 3.4 to 5.0 g/dL). No correlation between smudge-cell count and albumin level was observed (r = –0.005, P = .95). Only three (3%) of 98 patients in our series had an albumin level less than 3.5 g/dL—a cutoff previously associated with a poor outcome.^3,5 Interestingly, despite its presence in only three patients, a low albumin level was associated with a statistically significant shortened overall survival (hazard ratio = 2.1; 95% CI, 1.1 to 4.1; P = .018). In multivariate analysis including the other significant prognostic factors in the original analysis,² albumin level was not an independent predictor of overall survival (P = .21), possibly due to the low number of patients presenting with hypoalbuminemia in this cohort.

These data confirm previous studies suggesting that hypoalbuminemia, when present, is an adverse prognostic factor in CLL. However, the fact that few patients with early-stage disease have hypoalbuminemia at presentation (3% in our study; 4% in a large cohort [n = 2,081] of patients with CLL/small lymphocytic leukemia recently reported by M. D. Anderson⁵) clearly limits the prognostic utility of this finding to roughly one in 25 patients. Importantly, the serum albumin level does not appear to affect smudge-cell formation, inferring that smudge-cell formation is primarily related to the intrinsic properties of CLL cytoskeleton as originally reported by our group.⁶

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Go RS: Smudge cells, serum albumin, and prognosis in B-cell chronic lymphocytic leukemia. J Clin Oncol 27:e44; 2009.[Free Full Text]

2. Nowakowski GS, Hoyer JD, Shanafelt TD, et al: Percentage of smudge cells on routine blood smear predicts survival in chronic lymphocytic leukemia. J Clin Oncol 27:1844–1849, 2009.[Abstract/Free Full Text]

3. Levis A, Ficara F, Marmont F, et al: Prognostic significance of serum albumin in chronic lymphocytic leukemia. Haematologica 76:113–119, 1991.[Medline]

4. Wierda WG, O'Brien S, Wang X, et al: Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood 109:4679–4685, 2007.[Abstract/Free Full Text]

5. Tsimberidou AM, Wen S, O'Brien S, et al: Assessment of chronic lymphocytic leukemia and small lymphocytic lymphoma by absolute lymphocyte counts in 2,126 patients: 20 years of experience at the University of Texas M.D. Anderson Cancer Center. J Clin Oncol 25:4648–4656, 2007.[Abstract/Free Full Text]

6. Nowakowski GS, Hoyer JD, Shanafelt TD, et al: Using smudge cells on routine blood smears to predict clinical outcome in chronic lymphocytic leukemia: A universally available prognostic test. Mayo Clin Proc 82:449–453, 2007.[Abstract/Free Full Text]

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Related Article

• Smudge Cells, Serum Albumin, and Prognosis in B-Cell Chronic Lymphocytic Leukemia
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Related Correspondence

• Smudge Cells, Serum Albumin, and Prognosis in B-Cell Chronic Lymphocytic Leukemia
  Ronald S. Go
  JCO 2009 27: 44 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Nowakowski, G. S. Articles by Kay, N. E. PubMed PubMed Citation Articles by Nowakowski, G. S. Articles by Kay, N. E. Related Articles Related Article Related Correspondence Social Bookmarking                            What's this?