Bone Marrow Transplantation, (1998) 22 , 259–264  1998 Stockton Press All rights reserved 0268–3369/98 $12.00 http:/ / www.stockton-press.co.uk/ bmt High incidence of extramedullary relapse of AML after busulfan/cyclophosphamide conditioning and allogeneic stem cell transplantation DR Simpson 1 , TJ Nevill 1 , JD Shepherd 1 , HC Fung 1 , DE Horsman 2 , SH Nantel 1 , LM Vickars 3 , HJ Sutherland 1 , CL Toze 1 , DE Hogge 1 , HG Klingemann 1 , SC Naiman 4 and MJ Barnett 1 The Leukemia and Bone Marrow Transplantation Program of British Columbia: Division of 1 Hematology, 4 Hematopathology and 2 Laboratory Medicine, British Columbia Cancer Agency, Vancouver Hospital and Health Sciences Centre; and 3 St Paul’s Hospital, and the University of British Columbia, Vancouver, Canada Summary: While allogeneic stem cell transplantation (SCT) is curative for a significant number of patients with AML, relapse of disease within the bone marrow and/or extra- medullary (EM) sites following high-dose therapy con- tinues to limit the success of this treatment. Between October 1985 and December 1996, 81 adults underwent allogeneic SCT for de novo AML at our centre. Forty- two patients remain alive and free of leukaemia with a median follow-up of 50 months. The 5-year actuarial event-free survivals (EFS) for all patients and for those undergoing SCT in CR1 or with advanced disease were 46% (95% confidence interval (CI) 34–58%), 63% (CI 46–76%), and 19% (CI 7–36%), respectively. Twenty- two patients relapsed at a median of 8 (range 1.6–54.5) months with the actuarial risk of relapse for all, CR1 and advanced disease patients being 38%, (CI 27–52%), 23% (CI 13–40%) and 68% (CI 46–88%), respectively. Ten patients relapsed at EM sites; six of these (27% of relapses) had an isolated EM relapse at a median of 31 (range 8.5–54) months. Three of the patients with iso- lated EM relapse survived 24 months following relapse and two patients remain disease-free at 29+ and 33+ months. BuCy conditioning followed by allogeneic SCT in AML results in satisfactory EFS although there is a significant risk of late isolated EM relapse. Keywords: acute myelogenous leukemia; extramedullary relapse; allogeneic BMT Allogeneic stem cell transplantation (SCT) is an effective therapy for patients with AML. 1–3 Long-term event-free survival (EFS) can be achieved in approximately 60% of patients undergoing SCT in first complete remission (CR1) 4–9 and 25–30% of those with more advanced dis- ease. 1,2,4,10,11 However, there remains some controversy regarding the optimal transplant preparative regimen in AML. For patients transplanted in CR1, one randomized Correspondence: Dr TJ Nevill, Department of Medicine, Vancouver Hos- pital and Health Sciences Centre, 910 W. 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E3 Received 4 October 1997; accepted 13 March 1998 study demonstrated a regimen employing TBI to be superior to busulfan/cyclophosphamide (BuCy) condition- ing, 7 while another showed the regimens to be equivalent. 8 One of the contributing factors to an unsuccessful result with SCT regardless of the preparative regimen utilized is relapse, occurring in 20–25% and 30–50% of AML patients transplanted during CR1 or with advanced disease, respect- ively. 1,2,4,7,9 The site of relapse after a TBI-based prepara- tive regimen is usually the marrow with or without extra- medullary (EM) disease. 12 Isolated EM relapse occurred in only 13% of patients developing recurrent disease after TBI conditioning in one study. 12 Little is known about the risk of isolated EM relapse of AML following BuCy with a small number of such patients reported recently in a survey by the European Group for Blood and Marrow Transplan- tation (EBMT) of more than 3000 AML transplants. 13 The present review was prompted by the observation that sev- eral patients receiving allogeneic SCT after BuCy at our institution experienced isolated EM relapse. Patients and methods Patient characteristics Between October 1985 and December 1996, 81 patients with de novo AML underwent related-donor SCT; patient characteristics are shown in Table 1. Conditioning regimen A diagnostic lumbar puncture was performed on day -8 with the administration of cytosine arabinoside 30 mg/m 2 intrathecally. All patients (with one exception) then received modified BuCy 4 with doses based on the lesser of actual or ideal body weight. Busulfan was given at a dose of 1 mg/kg orally every 6 h for 4 days from days -7 to -4. Patients vomiting within 1 h of busulfan administration had the dose repeated and those vomiting two consecutive doses received subsequent doses via a naso-duodenal tube. Cyclophosphamide at a dose of 60 mg/kg was given i.v. over 2 h on days -3 and -2. One patient with pre-existing hepatic dysfunction was given a modified Bu (12 mg/kg) Cy (200 mg/kg) regimen. Patients routinely received phenytoin as anti-seizure prophylaxis while on busulfan