Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

TY - JOUR

T1 - Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

AU - Craddock, Charles

AU - Nagra, Sandeep

AU - Peniket, Andrew

AU - Brookes, Cassandra

AU - Buckley, Laura

AU - Nikolousis, Emmanouil

AU - Duncan, Nick

AU - Tauro, Sudhir

AU - Yin, John

AU - Liakopoulou, Effie

AU - Kottaridis, Panos

AU - Snowden, John

AU - Milligan, Donald

AU - Cook, Gordon

AU - Tholouli, Beni

AU - Littlewood, Tint

AU - Peggs, Karl

AU - Vyas, Paresh

AU - Clark, Fiona

AU - Cook, Mark

AU - MacKinnon, Stephen

AU - Russell, Nigel

PY - 2010/6

Y1 - 2010/6

N2 - BackgroundReduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown.Design and MethodsWe have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months.ResultsThe 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001).ConclusionsDisease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.

AB - BackgroundReduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versus-leukemia effect and long-term outcome post-transplant is unknown.Design and MethodsWe have characterized pre- and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months.ResultsThe 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001).ConclusionsDisease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versus-leukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.

KW - reduced intensity conditioning

KW - graft-versus-leukemia

KW - acute myeloid leukemia

KW - ACUTE MYELOGENOUS LEUKEMIA

KW - BONE-MARROW-TRANSPLANTATION

KW - VERSUS-HOST-DISEASE

KW - MYELODYSPLASTIC SYNDROME

KW - CYCLOSPORINE-A

KW - CONDITIONING REGIMEN

KW - COMPLETE REMISSION

KW - CLINICAL-TRIALS

KW - TOTAL-BODY

KW - RISK

U2 - 10.3324/haematol.2009.013920

DO - 10.3324/haematol.2009.013920

M3 - Article

C2 - 19951968

SN - 0390-6078

VL - 95

SP - 989

EP - 995

JO - Haematologica

JF - Haematologica

IS - 6

ER -