Percentage of smudge cells on routine blood smear predicts survival in chronic lymphocytic leukemia

Abstract

Purpose: Smudge cells are ruptured chronic lymphocytic leukemia (CLL) cells appearing on the blood smears of CLL patients. Our recent findings suggest that the number of smudge cells may have important biologic correlations rather than being only an artifact of slide preparation. In this study, we evaluated whether the smudge cell percentage on a blood smear predicted survival of CLL patients.

Patients and methods: We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocytes) on archived blood smears from a cohort of previously untreated patients with predominantly early-stage CLL enrolled onto a prospective observational study. The relationship between percentage of smudge cells, patient survival, and other prognostic factors was explored.

Results: Between 1994 and 2002, 108 patients were enrolled onto the study and had archived blood smears available for review; 80% of patients had Rai stage 0 or I disease. The median smudge cell percentage was 28% (range, 1% to 75%). The percentage of smudge cells was lower in CD38(+) versus CD38(-) patients (P = .019) and in Zap70-positive versus Zap70-negative patients (P = .028). Smudge cell percentage as a continuous variable was associated with prolonged survival (P = .042). The 10-year survival rate was 50% for patients with 30% or less smudge cells compared with 80% for patients with more than 30% of smudge cells (P = .015). In multivariate analysis, the percentage of smudge cells was an independent predictor of overall survival.

Conclusion: Percentage of smudge cells on blood smear is readily available and an independent factor predicting overall survival in CLL.

Fig 1.

Smudge cells on peripheral-blood smear of patient with chronic lymphocytic leukemia. The arrows show examples of smudge cells. The smudge cell percentage is estimated by counting 200 lymphocytes and/or smudge cells; the smudge cell number is then divided by total number of cells counted (smudge cells + intact lymphocytes) and multiplied by 100%.

Fig 2.

Smudge cell percentage in 108 patients with chronic lymphocytic leukemia (CLL). (A) Distribution of smudge cell percentage in the entire cohort. The presence of smudge cells on peripheral-blood smears of CLL patients is a constant feature of CLL with significant interpatient variability. The median smudge cell percentage was 28% (range, 1% to 75%) in our study. Only four patients (4%) had a smudge cell percentage within the 1% to 5% range. (B) Percentage of smudge cells in CD38^– and CD38⁺ patients. (C) Smudge cell percentage and CD38 expression as continuous variables. A distinct group of patients with a high percentage of smudge cells and CD38^– disease can be identified.

Fig 3.

Overall survival (OS) based on the percentage of smudge cells on blood smear. (A) Kaplan-Meier estimates of OS based on the percentage of smudge cells in the entire cohort. The 10-year survival rate was 50% v 80% for patients with smudge cell percentage ≤ 30% v more than 30%, respectively (P = .015). (B) Kaplan-Meier estimates of OS based on the percentage of smudge cells in patients with Rai stage 0 and I disease only. The 10-year survival rate was 61% v 84% for patients with smudge cell percentage ≤ 30% v more than 30%, respectively (P = .033). (C) Kaplan-Meier estimates of OS based on smudge cell percentage and CD38 expression. The 10-year survival of patients with CD38⁺ disease and less than 30% smudge cells was only 13% compared with 58%, 72%, and 85% for patients with CD38⁺ disease and ≥ 30% smudge cells, CD38^– disease and less than 30% smudge cells, and CD38^– disease and ≥ 30% smudge cells, respectively (P < .001).

Fig A1.

Kaplan-Meier estimate of overall survival (OS) of patients with slides available and not available for review. The estimated median OS of patients with archived slides and without archived slides was not significantly different between these two groups (13.2 v 12.2 years, respectively; P = .6).