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

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

Research output: Contribution to journalArticle

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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/m2/d for 3 d), intravenous cyclophosphamide (750 mg/m2/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.

Original languageEnglish (US)
Pages (from-to)355-363
Number of pages9
JournalBritish Journal of Haematology
Volume137
Issue number4
DOIs
StatePublished - May 1 2007

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ZAP-70 Protein-Tyrosine Kinase
B-Cell Chronic Lymphocytic Leukemia
Leukemia
Transplantation
Transplants
Disease-Free Survival
Survival Rate
Chimerism
Survival
Stem Cell Transplantation
Cyclophosphamide
Disease Progression
Multivariate Analysis
Bone Marrow
Tissue Donors
Lymphocytes
T-Lymphocytes
Biopsy

Keywords

  • Chronic lymphocytic leukaemia
  • Graft-versus-leukaemia
  • Non-myeloablative transplantation
  • ZAP-70

ASJC Scopus subject areas

  • Hematology

Cite this

Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. / Khouri, Issa F.; Saliba, Rima M.; Admirand, Joan; O'Brien, Susan; Lee, Ming S.; Korbling, Martin; Samuels, Barry I.; Giralt, Sergio; Lima, De Marcos; Keating, Michael J.; Champlin, Richard E.; Bueso-Ramos, Carlos.

In: British Journal of Haematology, Vol. 137, No. 4, 01.05.2007, p. 355-363.

Research output: Contribution to journalArticle

Khouri, Issa F. ; Saliba, Rima M. ; Admirand, Joan ; O'Brien, Susan ; Lee, Ming S. ; Korbling, Martin ; Samuels, Barry I. ; Giralt, Sergio ; Lima, De Marcos ; Keating, Michael J. ; Champlin, Richard E. ; Bueso-Ramos, Carlos. / Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. In: British Journal of Haematology. 2007 ; Vol. 137, No. 4. pp. 355-363.
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AU - Admirand, Joan

AU - O'Brien, Susan

AU - Lee, Ming S.

AU - Korbling, Martin

AU - Samuels, Barry I.

AU - Giralt, Sergio

AU - Lima, De Marcos

AU - Keating, Michael J.

AU - Champlin, Richard E.

AU - Bueso-Ramos, Carlos

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