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Graft‐ versus ‐leukaemia effect after non‐myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP‐70 in refractory chronic lymphocytic leukaemia
Author(s) -
Khouri Issa F.,
Saliba Rima M.,
Admirand Joan,
O'Brien Susan,
Lee MingS.,
Korbling Martin,
Samuels Barry I.,
Giralt Sergio,
Lima De Marcos,
Keating Michael J.,
Champlin Richard E.,
BuesoRamos Carlos
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06591.x
Subject(s) - medicine , fludarabine , transplantation , gastroenterology , cyclophosphamide , rituximab , oncology , immunology , chemotherapy , lymphoma
Summary 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.