A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease.
BACKGROUND
Many patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) do not have an human leukocyte antigen (HLA)-matched donor. Alternative donors, such as HLA mismatched family donors, are associated with higher rates of graft rejection and acute graft versus host disease (aGVHD) if T cells are not first depleted. We developed a new technique for HLA mismatched allogeneic HSCT using G-CSF primed bone marrow plus G-CSF-mobilized peripheral blood stem cells without ex vivo T cell depletion.


METHODS
In this study, 58 patients, including 33 with high-risk or advanced leukemia, were transplanted with cells from an HLA-haploidentical family donor with 1 - 3 mismatched loci. After conditioning, patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, in combination with G-CSF-mobilized peripheral blood stem cells, as well as GVHD prophylaxis.


RESULTS
All patients achieved sustained, full donor-type engraftment. The incidence of grade II-IV aGVHD was 37.9%, including 3 patients with grade III-IV aGVHD. The development of aGVHD was not associated with the extent of HLA disparity. Chronic GVHD was observed in 30 of 51 evaluable patients (65.4%). Fourteen patients died among whom 7 died of recurrent disease and 7 of transplant-related complications. Forty-four of the 58 patients survived, and 42 remained disease free at the time of a median follow-up of 12 months (3.5 to 39.5 months). The 2-year probabilities of disease-free survival were 74.8% and 69.3% for standard- and high-risk patients, respectively.


CONCLUSIONS
We developed a new method to use bone marrow from haploidentical family donors without ex vivo T cell depletion, in combination with G-PBSCs, as a source of stem cells even in cases of HLA mismatched transplantation.
Huang
Xiao-jun
XJ
Peking University Institute of Hematology, People's Hospital, Beijing 100044, China. xjhrm@medmail.com.cn
Han
Wei
W
Xu
Lan-ping
LP
Chen
Yu-hong
YH
Liu
Dai-hong
DH
Lu
Jin
J
Chen
Huan
H
Zhang
Yao-chen
YC
Jiang
Qian
Q
Liu
Kai-yan
KY
Lu
Dao-pei
DP
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D016179:Granulocyte Colony-Stimulating Factor