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.
journal_name
Leukemiajournal_title
Leukemiaauthors
de Lima M,Champlin RE,Thall PF,Wang X,Martin TG 3rd,Cook JD,McCormick G,Qazilbash M,Kebriaei P,Couriel D,Shpall EJ,Khouri I,Anderlini P,Hosing C,Chan KW,Andersson BS,Patah PA,Caldera Z,Jabbour E,Giralt Sdoi
10.1038/sj.leu.2405014subject
Has Abstractpub_date
2008-02-01 00:00:00pages
258-64issue
2eissn
0887-6924issn
1476-5551pii
2405014journal_volume
22pub_type
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