Epstein‐Barr virus lymphoproliferative disease (EBV‐LPD) following allogeneic stem cell transplantation (allo‐SCT) has a poor prognosis. We used a sensitive real‐time polymerase chain reaction (PCR) assay for quantitative detection of EBV‐DNA in plasma and serially measured EBV‐DNA levels to assess the response to treatment in allo‐SCT recipients with EBV‐LPD. Fourteen allo‐SCT recipients with EBV‐LPD who received a T cell‐depleted (TCD) sibling (n = 5) or matched unrelated donor (n = 9) graft were monitored from the time of EBV‐LPD diagnosis, during therapy and assessment of clinical response. Seven patients had complete responses of EBV‐LPD to therapy, of whom 21% (3 out of 14) survived beyond 6 months from EBV‐LPD diagnosis. Clinically responding patients showed a rapid decline of EBV‐DNA plasma levels within 72 h from the start of therapy. In contrast, all clinical non‐responders showed an increase of EBV‐DNA levels. Absolute EBV‐DNA levels at the time of EBV‐LPD diagnosis did not predict for response, but the pattern of EBV‐DNA levels within 72 h from the start of therapy (> 50% decrease versus increase) strongly predicted for clinical response (P = 0·001). Quantitative monitoring of EBV‐DNA levels from the start of and during therapy for EBV‐LPD rapidly and accurately predicts for response to therapy as early as within 72 h. It may thus provide a powerful tool to adjust and select treatment in individuals with EBV‐LPD following allo‐SCT.

Mantle cell lymphoma (MCL) is an aggressive neoplasm characterized by the deregulated expression of cyclin D1 by t(11;14). The molecular mechanisms responsible for MCL's clinical behavior remain unclear. The authors have investigated the expression of p53, E2F-1, and the CDK inhibitors p27 and p21 in 110 MCLs, relating their expression to proliferative activity (Ki-67). For comparison, they have similarly analyzed low-grade (12 MALT, 16 CLL/SLL) and high-grade (19 DLCL) lymphomas. p53 was detected more frequently in large-cell MCL (l-MCL; 5 of 7) than in classical MCL (s-MCL; 13 of 103) and DLCL (8 of 19). In MCL and DLCL, the percentage of E2F-1+ nuclei was high, correlating with high Ki-67 expression. Most MCLs (91 of 112) and DLCLs (12 of 19) showed a loss of p27; MALT and CLL/SLL, however, were p27 positive. Reverse transcription–polymerase chain reaction and in vitro protein degradation assays demonstrated that MCLs have normal p27 mRNA expression but increased p27 protein degradation activity via the proteasome pathway. Correlation of MCL p53 and p27 expression with clinical data showed an association between reduced overall survival rates and the overexpression of p53 (P = .001), the loss of p27 (P = .002), or both. Loss of p27 identified patients with a worse clinical outcome among p53 negative cases (P = .002). These findings demonstrated that MCL has a distinct cell cycle protein expression similar to that of high-grade lymphoma. The loss of p27 and the overexpression of p53 in MCL are prognostic markers that identify patients at high risk. The demonstration that low levels of p27 in MCL result from enhanced proteasome-mediated degradation should encourage additional clinical trials. (Blood. 2000;95:619-626)