Bone Marrow Transplantation (2001) 27, 1221–1225  2001 Nature Publishing Group All rights reserved 0268–3369/01 $15.00 www.nature.com/bmt Conditioning regimens Decitabine with allogeneic peripheral blood stem cell transplantation in the therapy of leukemia relapse following a prior transplant: results of a phase I study F Ravandi 1 , H Kantarjian 1 , A Cohen 1 , M Davis 1 , S O’Brien 1 , P Anderlini 1 , B Andersson 1 , D Claxton 1 , M Donato 1 , J Gajewski 1 , I Khouri 1 , M Korbling 1 , N Ueno 1 , D deVos 2 , R Champlin 1 and S Giralt 1 1 Department of Hematology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA; and 2 Pharmachemie BV, Haarlem, The Netherlands Summary: Relapse after allogeneic progenitor cell transplant is associated with a poor prognosis for patients with advanced leukemia, with few curative options available. Use of novel chemotherapeutic agents with limited tox- icity is warranted. We investigated the role of decitab- ine, a pyrimidine analogue with significant anti-leu- kemic effect and limited toxicity, in this setting. Fourteen patients with advanced acute leukemia or transformed chronic myelogenous leukemia (CML) who had failed previous allogeneic transplant were treated. Decitabine at doses of 100 mg/m 2 to 150 mg/m 2 given every 12 h for 5 days was followed by infusion of stem cells from the original donor 2 to 5 days after the com- pletion of chemotherapy. Dose of decitabine was esca- lated in cohorts of three patients based on the modified Fibonacci scheme. The primary study end-point was assessment of the toxicity of the regimen with secondary endpoints of response and survival. Eight patients responded with either a complete remission or partial hematological remission (absence of blasts in peripheral blood and bone marrow but with platelet count 100 × 10 9 /l). Toxicity was limited with no grade 3 or 4 toxicity directly attributable to the treatment. The median survival for all patients was 190 days (range 11 to 1215+ days). Decitabine at doses of 100 mg/m 2 to 150 mg/m 2 given every 12 h for 5 days, followed by stem cell infusion from the original donor was well tolerated, and was associated with acceptable myelosuppression. Current response data should encourage further study of this drug, either alone or in combination with other agents, for treatment of relapsed acute leukemia after an allogeneic transplant. Bone Marrow Transplantation (2001) 27, 1221–1225. Keywords: decitabine; allogeneic SCT; advanced leukemia Correspondence: Dr S Giralt, Department of Hematology, Box 65, Univer- sity of Texas – MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77027, USA Received 11 July 2000; accepted 7 February 2001 Despite significant advances in the understanding and treat- ment of leukemias over the past decade, the majority of patients with transformed CML and advanced acute leuke- mia cannot be cured. Allogeneic stem cell transplantation used as consolidation therapy, or for the treatment of relapsed disease, has the potential to cure some patients, but is associated with a high relapse rate. 1 Available options for treatment of relapse following allogeneic transplant are limited and include donor lymphocyte infusion (DLI), investigational and conventional salvage regimens, and a second transplant. 2 Conventional chemotherapy regimens achieve complete remissions in a minority of patients and are rarely durable. 1–3 Intensifying novel therapeutic agents for treatment of relapse after an allogeneic transplant may improve results. Methylation of CpG dinucleotide islands in human DNA, as maintained by the enzyme cytosine DNA methyltransfer- ase, has been the subject of intensive research. 4 Hyperme- thylation of promoter regions has emerged as an important mechanism of suppression of several genes including the calcitonin gene, p16, p15, Igf-2, c-abl and others, putatively involved in the control of growth of leukemic cells. 4 The inhibition of the enzyme DNA methyltransferase is associa- ted with hypomethylation, and reactivation of such tumor suppressor genes. 4 Decitabine (5-aza-2′-deoxycitidine; DAC) is a pyrim- idine analogue, initially synthesized in 1964. 5 Its anti-leu- kemic potential was first realized by Sorm and Vesely in 1968. 6 Recent studies have demonstrated that the anti-leu- kemic activity of decitabine, and its analogue 5-azacytidine, may be related to their ability to inhibit DNA methyl- transferase by forming covalent adducts with the enzyme. 7,8 The activation of silent genes is believed to be responsible for the induction of terminal differentiation of the leukemic cells leading to senescence and apoptosis. 7,9,10 Laboratory studies, carried out on the peripheral blood and bone mar- row cells of patients treated with decitabine has revealed phenotypic modification of the leukemic cells, with the reduction of expression of CD13 and CD33 and an increase in antigenic density of surface determinants of mature myeloid cells such as CD16 and CD11c. 11,12 Of interest, the expression of MHC class I molecules, HLA-DR and