Long-term outcomes of alemtuzumab-based reduced-intensity conditioned hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myelogenous leukemia secondary to myelodysplastic syndrome.

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted.

• Authors: Victoria T Potter, Pramila Krishnamurthy, Linda D Barber, Ziyi Lim, Michelle Kenyon, Robin M Ireland, Hugues de Lavallade, Abdel Dhouri, Judith C W Marsh, Robert Marcus, Stephen Devereux, Aloysius Ho, Antonio Pagliuca, Ghulam J Mufti
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 1 Pg. 111-7 (Jan 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 24216184 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Myeloablative Agonists
• Alemtuzumab

Topics

• Adult
• Aged
• Alemtuzumab
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Female
• Follow-Up Studies
• Graft vs Host Disease (prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Myeloid, Acute (etiology, immunology, mortality, therapy)
• Lymphocyte Transfusion
• Male
• Middle Aged
• Multivariate Analysis
• Myeloablative Agonists (therapeutic use)
• Myelodysplastic Syndromes (complications, immunology, mortality, therapy)
• Recurrence
• Siblings
• Survival Analysis
• Transplantation Conditioning (methods)
• Transplantation, Homologous
• Treatment Outcome
• Unrelated Donors