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[Experimental study of optimized H-2 haploidentical hematopoietic engraftment for the treatment of murine acute
1Department of Hematology, Nanfang Hospital, the First Military Medical University of PLA, Guangzhou 510515, China.
Objective:
To explore the critical dose of T lymphocyte for preserving graft versus leukemia (GVL) while preventing GVHD in murine acute leukemia model treated with H-2 haploidentical hematopoietic stem cell transplantation (HSCT).
Methods:
(C57BL/6 x 615) F1 (H-2bk) mice which was inoculated with L615 cells to develop leukemic murine model was the recipient. The healthy C57BL/6 (H-2b) mice was the donor. CD(34)(+) cells from bone marrow and CD(3)(+)cells from spleen of the donor were purified by miniMACS. The purity of CD(34)(+) cells and CD(3)(+) cells were (81.5 +/- 2.4)% and (95.4 +/- 2.9)% respectively. Sixty-nine recipient mice were divided into seven groups. Group A received no treatment, group B received TBI only, the rest groups were irradiated 9 Gy by (60)Co and transfused 10(5) CD(34)(+) cells or mixed with 10(7) (E), 10(8) (F), 1.5 x 10(8) (G) of CD(3)(+) cells respectively. The mice were raised for 60 days, The cause of death was identified by pathology.
Results:
All mice in group E survived more than 60 days being significantly longer than that in the rest groups (p < 0.0001). The chimerisms from donor were 100% in the mice survived > 60 days. Mice died of leukemia relapse in group D and group E were significantly less than those in group C (p < 0.001). Mice died from GVHD in group G were significantly more than those in group E and group F (p < 0.001).
Conclusions:
The leukemia relapse rate was highest in mice that were transplanted with CD(34)(+) cells alone. Those mice transfused with CD(3)(+) T lymphocyte in the graft higher than 10(8) cells died from the GVHD was significantly higher. The inclusive dosage of 5 x 10(7) CD(3)(+) T lymphocyte was enough to separate the GVHD from GVL.
