Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia.

Abstract

ZAP-70 (zeta-chain-associated protein 70 kDa) expression is associated with poor prognosis in patients with chronic lymphocytic leukaemia (CLL). This study evaluated the efficacy of non-myeloablative allogeneic stem cell transplantation in patients with advanced CLL and assessed the impact of ZAP-70 expression on the outcome. Thirty-nine sequential patients were included. All had previously been treated with fludarabine. All patients received a preparative regimen of fludarabine (30 mg/m(2)/d for 3 d), intravenous cyclophosphamide (750 mg/m(2)/d for 3 d), and high-dose rituximab. Immunohistochemical techniques on marrow biopsy samples were used to determine that ZAP-70 was expressed in 25 patients, whereas 13 other patients were ZAP-70 negative, and one was of indeterminate status. With a median follow-up time of 27 months, the estimated overall survival and current progression-free survival (CPFS) rates at 4 years were 48% and 44% respectively. Patients who were ZAP-70 positive had 56% survival, and their CPFS rate increased from 30% to 53% after a donor lymphocyte infusion. Multivariate analysis indicated that chemorefractory disease and mixed T cell chimerism at day 90, but not ZAP-70 positivity, were associated with the risk of disease progression after transplantation. These results demonstrate a potent graft-versus-leukaemia effect that can overcome the adverse prognostic effect of ZAP-70 expression.

• Authors: Issa F Khouri, Rima M Saliba, Joan Admirand, Susan O'Brien, Ming-S Lee, Martin Korbling, Barry I Samuels, Sergio Giralt, de Marcos Lima, Michael J Keating, Richard E Champlin, Carlos Bueso-Ramos
• Journal: British journal of haematology (Br J Haematol) Vol. 137 Issue 4 Pg. 355-63 (May 2007) ISSN: 0007-1048 [Print] England
• PMID: 17456058 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Biomarkers, Tumor
• Rituximab
• Cyclophosphamide
• ZAP-70 Protein-Tyrosine Kinase
• ZAP70 protein, human
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor (analysis)
• Chi-Square Distribution
• Combined Modality Therapy
• Cyclophosphamide (therapeutic use)
• Female
• Follow-Up Studies
• Graft vs Leukemia Effect
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, therapy)
• Male
• Middle Aged
• Rituximab
• Statistics, Nonparametric
• Survival Rate
• Transplantation, Homologous
• Treatment Outcome
• Vidarabine (analogs & derivatives, therapeutic use)
• ZAP-70 Protein-Tyrosine Kinase (analysis)