1. ¹Department of Stem Cell Transplantation and Cell Therapy, U.T.M.D. Anderson Cancer Center, Houston, TX, USA
2. ²Department of Biostatistics, U.T.M.D. Anderson Cancer Center, Houston, TX, USA
3. ³Department of Bone Marrow Transplantation, University of California, San Francisco, CA, USA
4. ⁴Texas Transplant Institute, Blood and Marrow Stem Cell Transplant Program, San Antonio, TX, USA

Correspondence: Dr M de Lima, Department of Stem Cell Transplantation and Cell Therapy, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 423, Houston, TX 77030-4009, USA. E-mail: mdelima@mdanderson.org

Received 21 May 2007; Revised 28 September 2007; Accepted 2 October 2007; Published online 8 November 2007.

Abstract

We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III–IV organ damage, engraftment failure or death within 30 days. 'Response' was engraftment and remission (CR) on day +30. We sought to determine the GO dose (2, 4 or 6 mg m^-2) giving the best trade-off between toxicity and response. All patients were not candidates for myeloablative regimens. Treatment plan: GO (day -12), fludarabine 30 mg m^-2 (days -5 to -2), melphalan 140 mg m^-2 (day -2) and HSCT (day 0). GVHD prophylaxis was tacrolimus and mini-methotrexate. Diagnoses were AML (n=47), MDS (n=4) or CML (n=1). Median age was 53 years (range, 13–72). All but three patients were not in CR. Donors were related (n=33) or unrelated (n=19). Toxicity and response rates at 4 mg m^-2 were 50% (n=4) and 50% (n=4). GO dose was de-escalated to 2 mg m^-2: 18% had toxicity (n=8) and 82% responded (n=36). 100-day TRM was 15%; one patient had reversible hepatic VOD. Median follow-up was 37 months. Median event-free and overall survival was 6 and 11 months. GO 2 mg m^-2 can be safely added to fludarabine/melphalan, and this regimen merits further evaluation.