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ZAP-70 May Not Predict Outcome after Mini-Transplant

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[2038] ZAP-70 Status May Not Predict Outcome after Non-Myeloablative

Allogeneic Transplantation (NMT) in Patients with Chronic Lymphocytic

Leukemia(CLL) Who Failed Conventional Chemotherapy. Session Type:

Poster Session 242-II

Issa F. Khouri, Rima M. Saliba, J. Keating, Joan Admirand,

O'Brien, E. Champlin, Buenos-Ramos Blood and

Marrow Transplantation, MD Cancer Cancer, Houston, TX, USA;

Leukemia, MD Cancer Center, Houston, TX, USA;

Hematopathology, MD Cancer Center, Houston, TX, USA

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%

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.

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