A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease

Xiao-jun Huang, Wei Han, Lan-ping Xu, Yu-hong Chen, Dai-hong Liu, Jin Lu, Huan Chen, Yao-chen Zhang, Qian Jiang, Kai-yan Liu, Dao-pei Lu
Chinese Medical Journal 2004, 117 (12): 1778-85

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.

RESULT: 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.

CONCLUSION: 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.

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