Clinical outcomes of late rather than early full-donor chimerism in patients with advanced lymphomas receiving nonmyeloablative allogeneic hematopoietic SCT.
Allogeneic hematopoietic SCT (HSCT) can ideally provide long-term remission in advanced lymphoma patients by capturing a graft-vs-tumor (GVT) effect. On the basis of a murine model, we attempted to optimize a GVT effect through nonmyeloablative therapy and HLA-matched related donor HSCT with intentional induction of mixed chimerism followed by prophylactic donor lymphocyte infusion. A total of 26 advanced lymphoma patients were separated into an early and late full-donor chimerism (FDC) group using a median of 45 days post-HSCT as the defining point for FDC. Upon generating these groups, analysis by Student's t-test demonstrated that they were statistically distinct in time to develop FDC (P<0.01). There was a trend toward improved CR rates in the late group relative to the early group (62 vs 31%; P=0.12). A trend toward improved progression-free survival at 5 years was also observed in the late compared to the early group by Kaplan-Meier analysis (38 vs 8%; P=0.081). However, this did not correlate to a significant overall survival benefit. In conclusion, these data support the observation from our mouse models that the most potent GVT effect occurs in mixed chimeras with late chimerism conversion.
Ting
D T
DT
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Spitzer
T R
TR
Chaudhary
A
A
Muzikansky
A
A
Colby
C
C
Power
K
K
McAfee
S
S
Ballen
K
K
Attar
E
E
Saidman
S L
SL
Preffer
F
F
Sykes
M
M
Dey
B R
BR
D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D005260:Female; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D015996:Survival Rate; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous