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


METHODS
We 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.


RESULTS
The 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).


CONCLUSIONS
Disease 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.
Craddock
Charles
C
Centre for Clinical Haematology, Main Drive, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. charles.craddock@uhb.nhs.uk
Nagra
Sandeep
S
Peniket
Andrew
A
Brookes
Cassandra
C
Buckley
Laura
L
Nikolousis
Emmanouil
E
Duncan
Nick
N
Tauro
Sudhir
S
Yin
John
J
Liakopoulou
Effie
E
Kottaridis
Panos
P
Snowden
John
J
Milligan
Donald
D
Cook
Gordon
G
Tholouli
Eleni
E
Littlewood
Tim
T
Peggs
Karl
K
Vyas
Paresh
P
Clark
Fiona
F
Cook
Mark
M
Mackinnon
Stephen
S
Russell
Nigel
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab