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Blood, 15 February 2008, Vol. 111, No. 4, pp. 1827-1833.
Prepublished online as a Blood First Edition Paper on November 29, 2007; DOI 10.1182/blood-2007-10-116582.
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Submitted October 11, 2007
Accepted November 15, 2007
In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from a matched sibling allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy in All patients : final results of the international ALL trial (MRC UKALL XII/ ECOG E2993)
Anthony H Goldstone*, Susan M. Richards, Hillard M. Lazarus, Martin S. Tallman, Georgina Buck, Adele K. Fielding, Alan K. Burnett, Raj Chopra, Peter H. Wiernik, Letizia Foroni, Elisabeth Paietta, Mark R. Litzow, David I Marks, Jill Durrant, Andrew McMillan, Ian M Franklin, Selina Luger, Niculae Ciobanu, and Jacob M. Rowe
UCL Hospitals, London, United Kingdom
Clinical Trial Service Unit, Oxford, United Kingdom
Ireland Cancer Center, University Hospitals of Cleveland, Cleveland, OH, United States
Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Royal Free & University College Medical School, London, United Kingdom
University of Wales, Cardiff, United Kingdom
Universty of Wales, Cardiff, United Kingdom
Our Lady of Mercy Cancer Center, New York Medical College, New York, NY, United States
Mayo Clinic College of Medicine, Rochester, MN, United States
Bristol Haematology & Oncology Centre, Bristol, United Kingdom
Nottingham University, Nottingham, United Kingdom
University of Glasgow, National Blood Transfusion Service, Glasgow, United Kingdom
Department of Haematology/Oncology, University of Pennsylvania, Philadelphia, PA, United States
Stem Cell Sciences, Inc, New York, NY, United States
Rambam Medical Center and Technion, Israel Institute for Technology, Haifa, Israel
* Corresponding author; email: anthony.goldstone{at}uclh.nhs.uk.
An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with ALL and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplant.
A donor versus no donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (p = .01) and the relapse rate was significantly lower (p = <.0001). The survival difference was significant in standard risk patients, but not in high-risk patients with a high non-relapse mortality rate in the high risk donor group. Patients randomized to chemotherapy had a higher 5-year OS, 46% than those randomized to autologous transplant, 37% (p = .03).
Matched related allogeneic transplants for ALL in first complete remission provide the most potent anti-leukemic therapy and considerable survival benefit for standard-risk patients. However, the transplant-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplant can replace consolidation/maintenance in any risk group. This study is registered at http://clinicaltrials.gov as NCT00002514.
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