title: Salvage therapy with ARA-C and gemtuzumab ozogamicin in AML patients relapsing after stem cell transplantation.
abstract: Acute myeloid leukemia (AML) relapse is often associated with a poor outcome, especially after allogeneic stem cell transplantation (Allo-SCT). In patients relapsing early after SCT treatment, options are further limited by the fear for increased toxicity. We report our experience with ARA-C and gemtuzumab ozogamicin (GO) combination in relapsed post-SCT AML patients. Therapy consisted of ARA-C (1 gr/m(2)) for 4 days followed by one dose of GO 9 mg/m(2) on day 5 and was supported by donor stem cells when possible. Responding patients not developing graft versus host disease (GVHD) were eligible for immunotherapy with donor lymphocyte infusion (DLI) or a second Allo-SCT. Sixteen patients, median age 53 years (range 31-63), are included in this analysis. Patients underwent SCT for high-risk AML (n = 11) or AML relapse (n = 5), and 81 % had an early post-SCT relapse. Responses were achieved in 60 % of evaluable patients (CR-5 CRp-4). Median probabilities of survival (OS) and event-free survival (EFS) in the entire cohort, responding and non-responding patients were 103 and 76 days, 183 and 97 days, and 79 and 16 days, respectively. At 1-year follow-up, 25 % of patients were alive; however, all had relapse. Treatment resulted in grade 3-4 neutropenia and thrombocytopenia in all patients, and 27 % each had grade 3-4 hyperbilirubinemia or elevation of liver enzymes. One patient died during treatment due to intracranial hemorrhage. Of the six patients proceeding to second SCT or receiving DLI, three patients developed mild veno-occlusive disease (VOD). Combination therapy with ARA-C and GO after SCT results in short-term disease control and limited toxicity and could be considered for patients who are candidates for further immunotherapy.
authors.affiliation: Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center, Tel Hashomer, Israel, maya.koren@sheba.health.gov.il.
authors.forename: Maya
authors.initials: M
authors.lastname: Koren-Michowitz
authors.forename: Hannah
authors.initials: H
authors.lastname: Maayan
authors.forename: Arie
authors.initials: A
authors.lastname: Apel
authors.forename: Noga
authors.initials: N
authors.lastname: Shem-Tov
authors.forename: Ronit
authors.initials: R
authors.lastname: Yerushalmi
authors.forename: Yulia
authors.initials: Y
authors.lastname: Volchek
authors.forename: Abraham
authors.initials: A
authors.lastname: Avigdor
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D000079982:Gemtuzumab; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D014184:Transplantation, Homologous; D017211:Treatment Failure
chemical_list: D000617:Aminoglycosides; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab