Original Article

Leukemia (2007) 21, 943–948. doi:10.1038/sj.leu.2404641; published online 15 March 2007

Response to donor lymphocyte infusions for chronic myeloid leukemia is dose-dependent: the importance of escalating the cell dose to maximize therapeutic efficacy

M P Simula1,2, S Marktel1,2, C Fozza1, J Kaeda1, R M Szydlo1, E Nadal1, M Bua1, A Rahemtulla1, E Kanfer1, D Marin1, E Olavarria1, J M Goldman1, J F Apperley1 and F Dazzi1

1Department of Hematology, Imperial College at Hammersmith Hospital, London, UK

Correspondence: Professor F Dazzi, Department of Hematology, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. E-mail: f.dazzi@imperial.ac.uk.

2These authors contributed equally to this work.

Received 4 December 2006; Revised 30 January 2007; Accepted 1 February 2007; Published online 15 March 2007.

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Abstract

Donor lymphocyte infusions (DLI) are an effective treatment for patients with chronic myeloid leukemia (CML) in relapse after allografting but the optimal cell dose has yet to be identified. To address this question, we investigated the factors affecting the dose required to achieve remission (effective cell dose, (ECD)) in 81 patients treated with an escalating dose regimen. The overall proportion of patients who achieved a molecular remission was 88%. The cumulative proportion of remitters increased significantly at each dose level. With a CD3+ cell dose less than or equal to107/kg, 56% of patients in molecular/cytogenetic relapse obtained molecular remission, whereas only 20% of those in hematologic relapse did so. At the same cell dose, 58% of patients who received lymphocytes from volunteer unrelated donors achieved remission, as compared to 29% of those who received DLI from sibling donors. We conclude that the response to DLI is dose-dependent and that the ECD is influenced by the quantity and phase of CML at relapse and degree of donor/recipient histocompatibility.

Keywords:

donor lymphocyte infusions, chronic myeloid leukemia, effective cell dose, escalating dose regimen, allogeneic stem cell transplantation

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