Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

Abstract

The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

• Authors: Sebastian Schneider, Annette Strumpf, Johannes Schetelig, Gerd Wunderlich, Gerhard Ehninger, Jörg Kotzerke, Martin Bornhäuser
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 21 Issue 10 Pg. 1754-60 (Oct 2015) ISSN: 1523-6536 [Electronic] United States
• PMID: 26001695 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article)
• Copyright: Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD
• Antigens, Neoplasm
• CD66 antigens
• Cell Adhesion Molecules
• Immunoconjugates
• Radioisotopes
• Alemtuzumab
• Rhenium
• Vidarabine
• Busulfan
• fludarabine

Topics

• Aged
• Alemtuzumab
• Allografts
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antigens, CD (immunology)
• Antigens, Neoplasm (immunology)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Busulfan (administration & dosage)
• Cell Adhesion Molecules (immunology)
• Combined Modality Therapy
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Feasibility Studies
• Female
• Graft vs Host Disease (epidemiology, etiology)
• Graft vs Leukemia Effect
• Humans
• Immunoconjugates (therapeutic use)
• Leukemia, Myeloid, Acute (drug therapy, radiotherapy, therapy)
• Lymphocyte Depletion (adverse effects, methods)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, radiotherapy, therapy)
• Neutropenia (etiology)
• Prospective Studies
• Radioimmunotherapy
• Radioisotopes (therapeutic use)
• Rhenium (therapeutic use)
• T-Lymphocytes (immunology)
• Transplantation Conditioning (adverse effects, methods)
• Vidarabine (administration & dosage, analogs & derivatives)