ORIGINAL ARTICLE High-dose melphalan with or without stem cell support before myeloablative allo-SCT for remission induction in patients with advanced relapsed or refractory AML A O’Meara 1 , T Pabst 2 , D Heim 1 , S Gerull 1 , C Bucher 1 , J Halter 1 , C Arber 1 , A Rovo` 1 , A Tichelli 1 , A Gratwohl 1 and M Stern 1 1 Division of Hematology, Department of Internal Medicine, University Hospital of Basel, Basel, Switzerland and 2 Department of Internal Medicine, Institute of Medical Oncology, Berne, Switzerland Treatment strategies for relapsed/refractory AML are limited and disappointing. Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM remission induction in highly advanced relapsed/refractory AML patients planned for allogeneic HSCT. A total of 23 patients with relapsed/ refractory AML were prospectively scheduled for HDM with or without stem cell support followed by myeloablative allogeneic HSCT. Patients included nine individuals with a history of previous HSCT (seven allogeneic, two auto- logous). A total of 18 patients (78%) achieved a leukemia- free state and an additional four had substantial reduction of the initial leukemia burden warranting treatment continua- tion. There were no differences between patients with or without immediate stem cell support regarding mucositis or other organ toxicity. A total of 20 patients proceeded to myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were alive at the last follow-up. Our study shows that HDM is effective in inducing a leukemia-free state in patients with highly advanced relapsed/refractory AML. Leukemia burden reduction with HDM, however, did not translate into improved OS. Bone Marrow Transplantation (2011) 46, 636–640; doi:10.1038/bmt.2010.181; published online 9 August 2010 Keywords: AML; melphalan; auto-SCT; allo-SCT Introduction Relapsed and/or refractory AML has an unsatisfactory prognosis and the therapeutic options are limited. Myelo- ablative allogeneic hematopoietic SCT (HSCT) may be used, however, its outcome is poor compared with patients treated in remission, 1 and the optimal pre-transplant conditioning regimen still remains controversial. Melpha- lan is a bifunctional alkylator that exerts non-cell cycle-specific cytotoxicity, 2 has a defined toxicity profile, 3 is well tolerated and has shown promising activity in patients with relapsed/refractory AML. 4 In patients trans- planted in first CR of childhood AML, high-dose melphalan (HDM) showed a similar efficacy to other preparative regimens, such as TBI and BU-based con- ditioning. 5 In a dose-finding study in adult patients, melphalan induced a CR in 75% of cases with relapsed/ refractory acute leukemia when given at a minimal dose of 140 mg/m 2 . 6 In another pilot study, HDM followed by allogeneic peripheral blood-related or unrelated HSCT was evaluated in the context of early relapse of AML, ALL, biphenotypic leukemia and chronic myelogenous leukemia in blast crisis. Transient remissions were observed, engraft- ment of both related and unrelated stem cells was assured, but no durable remissions were achieved. 7 Recently, Bug et al. proposed HDM re-induction chemotherapy and autologous stem cell support for patients with AML in first relapse. This trial proved that a large proportion of second CRs can be obtained without excessive treatment-related mortality. 8 Few data exist on the impact of HDM remission induction in AML patients planned for allo-HSCT. We analyzed the impact of HDM with and without stem cell support in even more advanced relapsed/refractory AML patients planned for myeloablative allogeneic HSCT. Patients and methods Patients Patients with relapsed or refractory AML were eligible. Ethics committee approved the treatment protocols of this single-center study and all patients gave informed consent to the treatment and analysis of outcome data. From March 2005 to April 2009, 12 males and 11 females aged 21–69 years (median 39 years) received HDM with or without stem cell support. In patients who had previously Received 15 December 2009; revised 21 April 2010; accepted 17 June 2010; published online 9 August 2010 Correspondence: Dr A O’Meara, Hematology, University Hospital of Basel, Petersgraben 4, Basel CH-4031, Switzerland. E-mail: AOmeara@uhbs.ch Bone Marrow Transplantation (2011) 46, 636–640 & 2011 Macmillan Publishers Limited All rights reserved 0268-3369/11 www.nature.com/bmt