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Therapy

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

Leukemia volume 22, pages 258–264 (2008)Cite this article

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.

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Authors and Affiliations

  1. Department of Stem Cell Transplantation and Cell Therapy, U.T.M.D. Anderson Cancer Center, Houston, TX, USA

    M de Lima, R E Champlin, G McCormick, M Qazilbash, P Kebriaei, D Couriel, E J Shpall, I Khouri, P Anderlini, C Hosing, B S Andersson, P A Patah, Z Caldera, E Jabbour & S Giralt

  2. Department of Biostatistics, U.T.M.D. Anderson Cancer Center, Houston, TX, USA

    P F Thall, X Wang & J D Cook

  3. Department of Bone Marrow Transplantation, University of California, San Francisco, CA, USA

    T G Martin III

  4. Texas Transplant Institute, Blood and Marrow Stem Cell Transplant Program, San Antonio, TX, USA

    K W Chan

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  1. M de Lima
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  10. D Couriel
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  11. E J Shpall
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  14. C Hosing
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  15. K W Chan
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  16. B S Andersson
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  18. Z Caldera
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  20. S Giralt
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Correspondence to M de Lima.

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de Lima, M., Champlin, R., Thall, P. et al. 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. Leukemia 22, 258–264 (2008). https://doi.org/10.1038/sj.leu.2405014

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