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
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954
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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 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 NegativeZAP-70 PositiveP 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%  
View Large

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.

Topics:
chemotherapy regimen, chronic b-cell leukemias, chronic lymphocytic leukemia, transplantation, homologous, zap-70 kinase, brachial plexus neuritis, fludarabine, graft-versus-host disease, chronic, cyclophosphamide, follow-up

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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