[A novel approach to HLA-mismatched transplantation].
OBJECTIVE
To investigate the new methods of human leukocyte antigen (HLA) mismatched transplantation in patients with hematologic malignancies.


METHODS
In this pilot study, 58 patients, 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with at least 1 of 6 loci mismatched. After conditioning, patients received non ex vivo, T cell-depleted grafts of G-CSF-primed bone marrow plus G-CSF-mobilized peripheral blood stem cells, as well as graft-versus-host-disease (GVHD) prophylaxis.


RESULTS
All patients achieved sustained, full donor type engraftment. The incidence of grades II-IV acute GVHD was 37.9% (22 of 58), and grades III and IV aGVHD developed in only 2 and 1 patients, respectively. Furthermore, there was no statistically significant association between the extents of HLA mismatching and the degree of aGVHD. Twenty six of 42 (61.9%) evaluable patients had developed chronic GVHD (cGVHD) with limited cGVHD in 15. Nine patients relapsed, all but one with advanced or refractory leukemia. Fourteen patients died (24.1%), of whom 7 died of recurrent diseases and 7 of transplant-related complications (TRM): main causes of TRM were infection(2), intestinal pneumonia(2), CMV encephalitis(1), hepatitis(1) and aGVHD (1). Forty-four of the 58 patients (75.9%) survived and 42 (72.4%) were disease free with a median follow-up of 10 months (range, 2 to 37.5 months). The 2-year probabilities of disease-free survival for patients with standard and high risks were 77.6% and 63.2% respectively, which showed that high-risk disease status at transplantation was associated with worse disease-free survival (P=0.04). The degree of HLA mismatching between the donor and the recipient was not related to event-free survival (P=0.57), nor was cell number infused and aGVHD (P=0.78, 0.94 respectively).


CONCLUSIONS
(1)HLA mismatched transplantation can be per formed without ex vivo T cell depletion. (2)Using G CSF mobilized PBSCs as a source of stem cells may be possible and safe even in HLA mismatched transplantation.
Huang
Xiao-jun
XJ
Institute of Hematology, Peking University People's Hospital, Beijing 100044, China. xjhrm@medmail.com.cn
Han
Wei
W
Xu
Lan-ping
LP
Chen
Huan
H
Liu
Dai-hong
DH
Chen
Yu-hong
YH
Jiang
Qian
Q
Lu
Jin
J
Liu
Kai-yan
KY
Ren
Han-yun
HY
Lu
Dao-pei
DP
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008297:Male; D010865:Pilot Projects