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

Biol Blood Marrow Transplant. 2014 Jan;20(1):111-7. doi: 10.1016/j.bbmt.2013.10.021. Epub 2013 Nov 8.

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.

Keywords: Acute myelogenous leukemia; Alemtuzumab; Myelodysplastic syndrome; Reduced intensity; Transplantatiom.

MeSH terms

  • 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
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Lymphocyte Transfusion
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myeloablative Agonists / therapeutic use*
  • Myelodysplastic Syndromes / complications
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / therapy*
  • Recurrence
  • Siblings
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors

Substances

  • Antibodies, Monoclonal, Humanized
  • Myeloablative Agonists
  • Alemtuzumab