Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study

Abstract

The proliferation index in mantle cell lymphoma (MCL) has not been validated in the context of aggressive therapy regimens in the rituximab era. We assessed Ki67 and PIM1 (a cell cycle-related gene upregulated in blastoid MCL) expression by immunohistochemistry in a phase II study Cancer and Leukemia Group B 59909 of aggressive chemotherapy and rituximab followed by autologous stem cell transplantation plus rituximab in untreated MCL patients <70 years of age. As a continuous variable or using a cutoff of 35%, higher image analysis (IA Ki67, n = 52) was associated with shorter progression free survival (PFS) (P < or = 0.030) and event free survival (EFS) (P < or = 0.017). PIM1 expression (n = 50) was associated with PFS (P = 0.033) and EFS (P = 0.043). Bivariate Cox models showed IA Ki67 and PIM1 were independent of clinical factors. High Ki67 (>35%) is an important independent prognostic marker in aggressively treated MCL in the rituximab era. PIM1 expression predicts poor outcome and, given its potential role as a therapeutic target, deserves further study.

Figures

Figure 1

MCL immunohistochemistry. (A) MCL with low Ki67 index of 3% (400 × original magnification); (B) MCL with Ki67 index of 80% (400 × original magnification); (C) Weakly positive PIM1 staining scored as 1+ (400 × original magnification); (D) Strongly positive PIM1 staining scored as 3+ (400 × original magnification). Insets show the scanned image of the biopsy at 1 ×.

Figure 2

Kaplan–Meier curves for PFS (A) and EFS (B) showing a statistically significant shorter survival for patients with high Ki67 index (dotted line) compared to those with a low Ki67 index (P values reflect the log-rank test.