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- Title
Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome.
- Authors
de Lima, M.; Champlin, R. E.; Thall, P. F.; Wang, X.; Martin, T. G.; Cook, J. D.; McCormick, G.; Qazilbash, M.; Kebriaei, P.; Couriel, D.; Shpall, E. J.; Khouri, I.; Anderlini, P.; Hosing, C.; Chan, K. W.; Andersson, B. S.; Patah, P. A.; Caldera, Z.; Jabbour, E.; Giralt, S.
- 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.
- Subjects
HEMATOPOIETIC stem cells; BONE marrow cells; TRANSPLANTATION of organs, tissues, etc.; MYELODYSPLASTIC syndromes; DYSPLASIA; BONE marrow diseases; TACROLIMUS; ANTINEOPLASTIC agents; MYELODYSPLASTIC syndromes treatment; AMINOGLYCOSIDES; ANTIGENS; ANTIMETABOLITES; ANTIVIRAL agents; CLINICAL trials; COMPARATIVE studies; GRAFT versus host reaction; HEMATOPOIETIC stem cell transplantation; HOMOGRAFTS; RESEARCH methodology; MEDICAL cooperation; MONOCLONAL antibodies; PROGNOSIS; RESEARCH; SURVIVAL; EVALUATION research; MYELOID leukemia; DISEASE remission; MELPHALAN; LEUKEMIA treatment
- Publication
Leukemia (08876924), 2008, Vol 22, Issue 2, p258
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/sj.leu.2405014