Favorable outcomes with alemtuzumab-conditioned unrelated donor stem cell transplantation in adults with high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in first complete remission.
BACKGROUND
Approximately 40% of adults with Philadelphia chromosome-negative acute lymphoblastic leukemia achieve long-term survival following unrelated donor hematopoietic stem cell transplantation in first complete remission but severe graft-versus-host disease remains a problem affecting survival. Although T-cell depletion abrogates graft-versus-host disease, the impact on disease-free survival in acute lymphoblastic leukemia is not known.


METHODS
We analyzed the outcome of 48 adults (median age 26 years) with high-risk, Philadelphia-chromosome-negative acute lymphoblastic leukemia undergoing T-cell depleted unrelated donor-hematopoietic stem cell transplantation (67% 10 of 10 loci matched) in first complete remission reported to the British Society of Blood and Marrow Transplantation Registry from 1993 to 2005.


RESULTS
T-cell depletion was carried out by in vivo alemtuzumab administration. Additional, ex vivo T-cell depletion was performed in 21% of patients. Overall survival, disease-free survival and non-relapse mortality rates at 5 years were 61% (95% CI 46-75), 59% (95% CI 45-74) and 13% (95% CI 3-25), respectively. The incidences of grades II-IV and III-IV acute graft-versus-host disease were 27% (95% CI 16-44) and 10% (95% CI 4-25), respectively. The actuarial estimate of extensive chronic graft-versus-host disease at 5 years was 22% (95%CI 13-38). High-risk cytogenetics at diagnosis was associated with a lower 5-year overall survival (47% (95% CI 27-71) vs. 68% (95% CI 44-84), p=0.045).


CONCLUSIONS
T-cell depleted hematopoietic stem cell transplantation from unrelated donors can result in good overall survival and low non-relapse mortality for adults with high-risk acute lymphoblastic leukemia in first complete remission and merits prospective evaluation.
Patel
Bella
B
Department of Haematology, Royal Free and University College London Medical School, and BSBMT Data Registry, Guy's Hospital, London, UK.
Kirkland
Keiren E
KE
Szydlo
Richard
R
Pearce
Rachel M
RM
Clark
Richard E
RE
Craddock
Charles
C
Liakopoulou
Effie
E
Fielding
Adele K
AK
Mackinnon
Stephen
S
Olavarria
Eduardo
E
Potter
Mike N
MN
Russell
Nigel H
NH
Shaw
Bronwen E
BE
Cook
Gordon
G
Goldstone
Anthony H
AH
Marks
David I
DI
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D012042:Registries; D012074:Remission Induction; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate / Q000639:trends; D019172:Transplantation Conditioning; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab