Early full donor myeloid chimerism after reduced-intensity stem cell transplantation using a combination of fludarabine and busulfan.
OBJECTIVE
The aim of this study was to evaluate lineage-specific chimerism reconstitution after reduced-intensity allogeneic stem cell transplantation (RIST) using a combination of fludarabine (30 mg/m2 for 6 days) and busulfan (4 mg/kg for 2 days).


METHODS
We prospectively enrolled 8 consecutive patients with hematologic malignancies who were not candidates for conventional transplantation because of either high age or organ dysfunction. Host-donor chimerism was evaluated using polymerase chain reaction-based amplification of a polymorphic short tandem repeat region.


RESULTS
All of our patients achieved engraftment within a median of 11 days after transplantation. On day 30, full donor myeloid cell chimerism (>90%) was achieved in 7 patients whereas full donor T-cell chimerism was achieved in only one patient. Thus, in contrast to other reported results, full donor chimerism was achieved earlier in the myeloid lineage than the T-cell lineage. On day 60, however, T-cell chimerism caught up with myeloid chimerism. Two patients developed grade II-IV acute graft-versus-host disease (GVHD) before the detection of full donor T-cell chimerism.


CONCLUSIONS
Our findings suggest that the kinetics of lineage-specific chimerism depend on the agents used in the conditioning regimen, and may provide insight into the chimerism kinetics and pathogenesis of GVHD. Thus, the strategy for controlling immunosuppression after RIST should be modified according to the type of conditioning regimen applied.
Niiya
H
H
Hematopoietic Stem Cell Transplant Unit, National Cancer Center Hospital, Tokyo, Japan.
Kanda
Y
Y
Saito
T
T
Ohnishi
T
T
Kanai
S
S
Kawano
Y
Y
Kamijo
K
K
Iizuka
A
A
Yakushijin
K
K
Ueda
K
K
Chizuka
A
A
Iijima
K
K
Ohnishi
M
M
Nakai
K
K
Makimoto
A
A
Tanosaki
R
R
Tobinai
K
K
Wakasugi
H
H
Takaue
Y
Y
Mineishi
S
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002066:Busulfan / Q000008:administration & dosage*; D019070:Cell Lineage / Q000187:drug effects; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology*; D011446:Prospective Studies; D018183:Transplantation Chimera; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives
D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine