Results of genoidentical hemopoietic stem cell transplantation with reduced intensity conditioning for acute myelocytic leukemia: higher doses of stem cells infused benefit patients receiving transplants in second remission or beyond--the Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation.
OBJECTIVE
Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known.


METHODS
From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CR1), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in 91% of patients and low-dose (< 4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1x 10(8)/kg and 5.8x 10(6)/kg, respectively.


RESULTS
Overall, 2-year leukemia-free survival (LFS) was 41% +/- 4% and it was 46% +/- 5% for patients receiving a higher cell dose (> 9.1x 10(8)/kg) and 37% +/- 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 +/- 8 versus 20 +/- 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes.


CONCLUSIONS
Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than in CR1.
Gorin
Norbert-Claude
NC
Department of Haematology and Cell Therapy, Hopital Saint-Antoine, Asistance Publique Hopitaux de Paris and Université Paris 6, Pierre et Marie Curie, France. norbert-claude.gorin@sat.aphp.fr
Labopin
Myriam
M
Boiron
Jean-Michel
JM
Theorin
Niklas
N
Littlewood
Tim
T
Slavin
Shimon
S
Greinix
Hildegard
H
Cahn
Jean Yves
JY
Alessandrino
E Paolo
EP
Rambaldi
Alessandro
A
Nagler
Arnon
A
Polge
Emmanuelle
E
Rocha
Vanderson
V
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000008:administration & dosage; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
D018952:Antigens, CD34