1. ¹Département d'hématologie et oncologie, Hôpital Mignot, Versailles, Université de Versailles-Saint Quentin en Yvelines, France
2. ²Laboratoire universitaire Pierre et Marie Curie-Paris 6, INSERM URMS 736, Les Cordeliers & AP-HP, Hôpital Hôtel Dieu, Département d'oncologie et hématologie, Paris, France
3. ³Département d'hématologie clinique, Hôpital Saint Louis, Université Paris 7, Bobigny, France
4. ⁴Département d'hématologie, Hôpital Percy, Clamart, Université Paris 11, Bobigny, France
5. ⁵Département d'hématologie, Hôpital Edouard Herriot, Université Lyon, Lyon, France
6. ⁶Département d'hématologie, Centre Henri Becquerel, Université de Rouen, Rouen, France
7. ⁷Département d'hématologie, Centre Paoli Calmettes, Université de Marseille, Marseille, France
8. ⁸Département d'hématologie, Hôpital Henri Mondor, Université Paris 12, Créteil, France
9. ⁹Département d'hématologie, Hôpital Dupuytren, Université de Limoges, Limoges, France
10. ¹⁰Département d'hématologie, Hôpital Clemenceau, Université de Caen, Caen, France
11. ¹¹Département d'hématologie, Hôpital Avicennes, Université Paris 13, Bobigny, France
12. ¹²Département d'hématologie, Hôpital Necker, Université Paris 5, France
13. ¹³Département d'hématologie, Hôpital Claude Huriez, Université de Lille 2, France
14. ¹⁴Département de Bio statistique et Informatique, Hôpital Saint Louis, Université Paris 7, France

Correspondence: Professor S Castaigne, Service d'hématologie et oncologie, Centre Hospitallier de Versailles, Hôpital Mignot, 177 rue de Versailles, Le Chesnay, Versailles 78150, France. E-mail: scastaigne@ch-versailles.fr

Received 25 May 2006; Revised 31 August 2006; Accepted 6 September 2006; Published online 19 October 2006.

Abstract

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m² on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m² on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia <500/l and thrombocytopenia <50 000/l were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.