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 Negative . | ZAP-70 Positive . | P value . |
|---|---|---|---|
| No. Pts | 8 | 19 | |
| Age (range) | 58 (45–69) yrs | 53 (34–72) yrs | 0.36 |
| Time Dx to NMT | 4.5 yrs | 4.5 yrs | 0.6 |
| No. Prior Chemoregimens | 3 (2–5) | 3 (2–8) | 0.7 |
| No. Pts in Richter | 1 | 6 | 0.3 |
| Status at NMT CR/PR/NR | 1/3/4 | 1/12/6 | 0.18 |
| Donor: | |||
| Matched Sibling | 7 | 16 | 0.6 |
| Unrelated | 1 | 3 | |
| #Pts requiring DLI | 3 | 9 | 0.4 |
| Final Response | |||
| CR/PR | 6/1 | 15/0 | 0.6 |
| NR/NE | 1/0 | 3/1 | |
| Relapse Post CR | 1 | 0 | |
| Follow-up Time | 11 (9–47) mos | 37 (13–75) mos | |
| Survival | |||
| 1.5- year | 83% | 84% | 0.7 |
| 4- year | NA | 64% | |
| Current PFS | 56% (1.5 yr) | 65% (4 yr) | |
| Causes of Death | PD(1), cGVHD(1) | PD(2), cGVHD(2), Infection(2) | |
| GVHD grade II–IV | 37% | 39% |
| . | ZAP-70 Negative . | ZAP-70 Positive . | P value . |
|---|---|---|---|
| No. Pts | 8 | 19 | |
| Age (range) | 58 (45–69) yrs | 53 (34–72) yrs | 0.36 |
| Time Dx to NMT | 4.5 yrs | 4.5 yrs | 0.6 |
| No. Prior Chemoregimens | 3 (2–5) | 3 (2–8) | 0.7 |
| No. Pts in Richter | 1 | 6 | 0.3 |
| Status at NMT CR/PR/NR | 1/3/4 | 1/12/6 | 0.18 |
| Donor: | |||
| Matched Sibling | 7 | 16 | 0.6 |
| Unrelated | 1 | 3 | |
| #Pts requiring DLI | 3 | 9 | 0.4 |
| Final Response | |||
| CR/PR | 6/1 | 15/0 | 0.6 |
| NR/NE | 1/0 | 3/1 | |
| Relapse Post CR | 1 | 0 | |
| Follow-up Time | 11 (9–47) mos | 37 (13–75) mos | |
| Survival | |||
| 1.5- year | 83% | 84% | 0.7 |
| 4- year | NA | 64% | |
| Current PFS | 56% (1.5 yr) | 65% (4 yr) | |
| Causes of Death | PD(1), cGVHD(1) | PD(2), cGVHD(2), Infection(2) | |
| GVHD grade II–IV | 37% | 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.
Author notes
Corresponding author
2005, The American Society of Hematology
2005
