ZAP-70 Status May Not Predict Outcome after Non-Myeloablative Allogeneic Transplantation (NMT) in Patients with Chronic Lymphocytic Leukemia(CLL) Who Failed Conventional Chemotherapy.

Abstract

In aggressive disease, the CLL cells usually express the 70-kD zeta-associated protein (ZAP-70). We used immunohistochemical techniques and routinely fixed, paraffin-embedded tissue to survey ZAP-70 expression in patients (pts) with CLL who received a NMT, as previously described (Modem Pathol 17:954, 2004). All cases were reviewed independently by two authors. Cytoplasmic staining of non-neoplastic, reactive T cells served as an internal control in each case. Neoplasms (Pax-5 +) demonstrating ZAP-70 cytoplasmic staining in greater than 20% of tumor cells were considered positive. Pts were eligible for NMT if they had failed fludarabine-based conventional therapy. The conditioning regimen prior to NMT consisted of fludarabine, cyclophosphamide and rituximab. Twenty nine pts were treated. The pts characteristics and outcome were as follows:ZAP-70 NegativeZAP-70 PositiveP valueNo. Pts819Age (range)58 (45–69) yrs53 (34–72) yrs0.36Time Dx to NMT4.5 yrs4.5 yrs0.6No. Prior Chemoregimens3 (2–5)3 (2–8)0.7No. Pts in Richter160.3Status at NMT CR/PR/NR1/3/41/12/60.18Donor:Matched Sibling7160.6Unrelated13#Pts requiring DLI390.4Final ResponseCR/PR6/115/00.6NR/NE1/03/1Relapse Post CR10Follow-up Time11 (9–47) mos37 (13–75) mosSurvival1.5- year83%84%0.74- yearNA64%Current PFS56% (1.5 yr)65% (4 yr)Causes of DeathPD(1), cGVHD(1)PD(2), cGVHD(2), Infection(2)GVHD grade II–IV37%39%These data suggest that NMT may overcome the negative prognostic impact of ZAP-positivity in CLL. Controlled trials are needed to confirm these results in a larger number of patients.