Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin.

Abstract

We prospectively evaluated 2 postconsolidation strategies, administered according to the mobilization outcome, in 72 acute myeloid leukemia (AML) fit elderly patients, achieving complete remission after the first high-dose cytarabine-based induction. Autologous stem cell transplantation (ASCT) was performed in patients collecting ≥3 × 10(6) CD34(+)/kg and low-dose gemtuzumab ozogamicin (GO) was performed in poor mobilizers (collecting <3 × 10(6) CD34(+)/kg). Fifty-five patients (76.3%) underwent peripheral blood stem cell (PBSC) mobilization, after first consolidation, and 24 of 55 (44%) collected >3 × 10(6) CD34(+) cells/kg. Among the 55 patients eligible for PBSC mobilization, 7 did not receive the planned treatment, 23 were allocated for ASCT, and 25 were allocated for GO on an intention-to-treat basis. With a median follow-up of 70 months (range, 24 to 124), 20 of 55 patients are alive, 18 of them in continuous complete remission. The 8-year overall survival (OS) and disease-free survival (DFS) are, respectively, 35.9% (95% confidence interval [CI] 24% to 49.8%) and 31.2% (95% CI, 21% to 43.8%), median OS and DFS were 22 and 16 months, respectively. In multivariate analysis, postconsolidation treatment and hyperleukocytosis (WBC > 50,000/μL) significantly predicted OS and DFS, whereas secondary AML was significantly associated with a higher relapse rate (83.4% versus 54% of de novo AML). Patients with hyperleukocytosis had 0% 3-year OS versus the 46% (at 8 years) in patients without hyperleukocytosis (P = .01); 57% of patients in the GO arm are alive at 8 years, compared with 25.4% of patients in the ASCT arm, who had an overall relative risk (RR) of death of 2.6 (95% CI, 1.2 to 5.8; P = .02). DFS at 8 years was 45.3% in patients receiving GO, compared with 26% in ASCT arm (RR, 2.1; 95% CI, 1 to 4.3; P = .05). Our study outlines low feasibility and efficacy of ASCT in elderly AML patients, whereas postconsolidation with GO appears safe and effective in this unfavorable setting. The study was registered at Umin Clinical Trial Registry (www.umin.ac.jp/ctr), number R000014052.

• Authors: Debora Capelli, Martina Chiarucci, Antonella Poloni, Francesco Saraceni, Giorgia Mancini, Silvia Trappolini, Emanuela Troiani, Mauro Montanari, Ilaria Scortechini, Massimo Offidani, Serena Rupoli, Anna Rita Scortechini, Guido Gini, Giancarlo Discepoli, Pietro Leoni, Attilio Olivieri
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 9 Pg. 1399-406 (Sep 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 24880020 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Aminoglycosides
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Gemtuzumab

Topics

• Aminoglycosides (administration & dosage, therapeutic use)
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Disease-Free Survival
• Feasibility Studies
• Female
• Gemtuzumab
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, mortality)
• Male
• Prospective Studies
• Transplantation Conditioning (methods)