Long-Term Outcomes of Alemtuzumab-Based Reduced-Intensity Conditioned Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Secondary to Myelodysplastic Syndrome

TY - JOUR

T1 - Long-Term Outcomes of Alemtuzumab-Based Reduced-Intensity Conditioned Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Secondary to Myelodysplastic Syndrome

AU - Potter, Victoria T.

AU - Krishnamurthy, Pramila

AU - Barber, Linda D.

AU - Lim, ZiYi

AU - Kenyon, Michelle

AU - Ireland, Robin M.

AU - de Lavallade, Hugues

AU - Dhouri, Abdel

AU - Marsh, Judith C.W.

AU - Marcus, Robert

AU - Devereux, Stephen

AU - Ho, Aloysius

AU - Pagliuca, Tony

AU - Mufti, Ghulam J.

PY - 2014/1

Y1 - 2014/1

N2 - 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 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. 

AB - 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 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. 

KW - Acute myelogenous leukemia

KW - Myelodysplastic syndrome

KW - Reduced intensity

KW - Transplantatiom

KW - Alemtuzumab

KW - ACUTE MYELOID-LEUKEMIA

KW - BONE-MARROW-TRANSPLANTATION

KW - VERSUS-HOST-DISEASE

KW - IMMUNE RECONSTITUTION

KW - UNRELATED DONORS

KW - ADULT PATIENTS

KW - SURVIVAL

KW - REGIMENS

KW - AGE

KW - REMISSIONS

U2 - 10.1016/j.bbmt.2013.10.021

DO - 10.1016/j.bbmt.2013.10.021

M3 - Article

SN - 1083-8791

VL - 20

SP - 111

EP - 117

JO - BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

JF - BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

IS - 1

ER -