ORIGINAL ARTICLE The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients B Sirohi, R Powles 1 , J Treleaven, S Kulkarni, R Saso, M Potter, M Ethell, G Morgan, S Singhal 2 and J Mehta 2 Leukaemia Unit, The Royal Marsden Hospital, Surrey, UK A total of 100 adults with ALL in first CR received melphalan (110 mg/m 2 ) with TBI followed by autologous marrow (n ¼ 35) or single-agent melphalan (200mg/m 2 ) followed by autologous blood stem cells (n ¼ 65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-pre- dnisone was administered for 2 years. Six patients, all TBI recipients (P ¼ 0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, 44 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2–3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (Po0.0001), and 7-year DFS probabilities of 73, 36 and 7% (Po0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (Po0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL. Bone Marrow Transplantation (2008) 42, 105–112; doi:10.1038/bmt.2008.95; published online 14 April 2008 Keywords: 6-mercaptopurine; autotransplantation; high- dose melphalan; methotrexate; prednisone; vincristine Introduction We have shown 1,2 that results of autologous hematopoietic stem cell transplantation (HSCT) in adult ALL 3–14 can be improved by administering post transplant maintenance chemotherapy with 6-mercaptopurine (6-MP), methotrex- ate and vincristine-prednisone. A recent review of auto- logous HSCT in ALL 15 suggested that the value of autotransplantation is likely to be underestimated in ALL. That conclusion is in keeping with the findings of a registry report that showed that survival after autologous HSCT was comparable to that after allogeneic HSCT from unrelated donors in ALL patients. 16 However, a major recent cooperative ALL study 17 found autotransplantation to be inferior to chemotherapy. There was no provision for maintenance therapy after autologous HSCT in this study. As conventional autologous HSCT is unlikely to be explored in ALL in future studies after these negative findings, we undertook a final review of our 20-year experience of post-autograft maintenance chemotherapy in ALL. Patients and methods All consecutive patients over the age of 15 who were autografted for ALL in first CR between July 1984 and February 2003 at the Leukaemia Unit of the Royal Marsden Hospital were included. All data were gathered and updated prospectively on a continuous basis. 18 Transplantation was performed as part of a standard treatment approach to adult ALL. Any research protocols that patients participated in during the course of the treatment were approved by the Ethics Committee of the Royal Marsden Hospital. All patients gave informed consent for transplantation. Table 1 shows patient char- acteristics. Received 22 December 2007; revised 13 February 2008; accepted 5 March 2008; published online 14 April 2008 Contributors: RP thought of using post transplant maintenance chemotherapy and designed the original treatment regimen. JM modified the treatment regimen and developed sequential high-dose therapy. BS, RP, JT, SS and JM wrote the paper. All authors cared for the patients, and reviewed and modified the paper. Correspondence: Dr J Mehta, Division of Hematology/Oncology, Northwestern University Medical School, 676 North St Clair Street, Suite 850, Chicago, IL 60611-2927, USA. E-mail: j-mehta@northwestern.edu 1 Current address: Parkside Oncology Clinic, Wimbledon, UK. 2 Current address: Division of Hematology/Oncology, The Feinberg School of Medicine, The Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA. Bone Marrow Transplantation (2008) 42, 105–112 & 2008 Macmillan Publishers Limited All rights reserved 0268-3369/08 $30.00 www.nature.com/bmt