Published online 31 July 2009
Haematologica, Vol 94, Issue 10, 1399-1406 doi:10.3324/haematol.2009.008649
Copyright © 2009 by Ferrata Storti Foundation

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Acute Lymphoblastic Leukemia

Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission

Bella Patel¹, Keiren E. Kirkland², Richard Szydlo³, Rachel M. Pearce², Richard E. Clark⁴, Charles Craddock⁵, Effie Liakopoulou⁶, Adele K. Fielding¹, Stephen Mackinnon¹, Eduardo Olavarria³, Mike N. Potter⁷, Nigel H. Russell⁸, Bronwen E. Shaw⁹, Gordon Cook¹⁰, Anthony H. Goldstone¹¹, David I. Marks¹²

¹ Department of Haematology, Royal Free and University College London Medical School, London
² BSBMT Data Registry, Guy’s Hospital, London
³ Department of Haematology, Imperial College London, Hammersmith Hospital Campus, London
⁴ Department of Haematology, Royal Liverpool University Hospital, Liverpool
⁵ Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham
⁶ Haematology and Transplant Unit, The Christie, Manchester, UK, Department of Haematology, Imperial College London, Hammersmith Hospital Campus, London
⁷ Section of Haemato-oncology, Royal Marsden Hospital NHS Trust, Surrey
⁸ The Centre for Clinical Haematology, Nottingham University Hospital (City Campus)
⁹ Section of Haemato-oncology, Royal Marsden Hospital NHS Trust, Surrey, UK and Anthony Nolan Trust, London
¹⁰ St James's Institute of Oncology, Leeds Teaching Hospitals Trust
¹¹ Department of Haematology, University College London Hospital, London
¹² Adult BMT Unit, United Bristol Healthcare Trust, Bristol, UK

Correspondence: David Marks, Department of Molecular and Cellular Medicine, University Hospitals Bristol Foundation Trust, Bristol BS2 8BJ, UK. E-mail:David.Marks{at}ubht.nhs.uk

Background: Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known.

Design and Methods: We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005.

Results: T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46–75), 59% (95% CI 45–74) and 13% (95% CI 3–25), respectively. The incidences of grades II–IV and III–IV acute graft-versus-host disease were 27% (95% CI 16–44) and 10% (95% CI 4–25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13–38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27–71) vs. 68% (95% CI 44–84), p=0.045).

Conclusions: T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.

Key words: adult acute lymphoblastic leukemia, stem cell transplantation, T-cell depletion.

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