The Effect of HLA-Cw in Haploidentical Stem Cell Transplantation.

Abstract Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a potential curative treatment for patients with malignant hematological disease. However Allo-HSCT limited by the availability of a suitably matched donor. With only 30–40% of patients having a matched-related donor available, haploidentical transplantation may increase the applicability of Allo-HSCT. The high incidence of severe GVHD is a barrier of the application of haploidentical HSCT. KIR ligand was HLA-Cw or HLA-Bw4.in our study, we detected HLA-Cw loci gene of donors and receipts with PCR-SSP who received haploidentical-HSCT. 21 patients with malignant hematologic disease, age 9–47 (median 24 year), who needed urgent transplant but neither HLA-identical sibling donors nor HLA-matched unrelated donors available, received non-T cell depleted haploidentic HSCT between July, 2002 to March 2006. patients were classified as follows AML 7 (standard risk 3, high risk 4), ALL6 (standard risk 2, high risk 4), CML 8 (4 in CP, 4 in AP or BP). All donors were HLA-haploidentical relatives who had at least two major histocompatibility complex antigen mismatched with the recipients including offspring, sibling and mother. All patients underwent haplo-HSCT with G-CSF primed BM or PB as stem cells. donors received G-CSF(300ug/12h×5d) from −5d, bone marrow cells were collected at −2d, PBSC were collected at −1d if CD34+ cells less than 4×106/kg of recipient’s body weight. The CD34+ cells in graft of HLA-Cw matched group were (5.43±1.59)×106/kg of recipient’s body weight. HLA-Cw mismatched group were (6.54±1.53)×106/kg of recipient’s body weight(P>0.05). CD3+T cells in graft of HLA-Cw matched group were (0.46±0.08)×108/kg of recipient’s body weight. HLA-Cw mismatched group were (1.89±1.15) ×108/kg(P<0.05). Recipients were prepared for transplantation with different conditioning regimens according to the type of disease. Myeloid leukemia regimen: MeCCNU 250mg/m2 −10d, Ara-C 2g/m2 q12h, from −9d to −8d, Bu 4mg/kg, from −7d to −5d, Cy 1.8g/m2.d, from −4d to −3d. Lymphoblastic leukemia regimen: MeCCNU 250mg/m2 −8d, Total-body irradiation(TBI) 8Gy −7d, Ara-C 2g/m2 q12h, from −6d to −5d, Cy 1.8g/m2.d, from −4d to −3d. All the patients were given hydration, alkalization, and given mesna to prevent hemorrhage cystitis. All patients received GVHD prophylaxis consisting of Cyclosporine(CSA), Methotrexate(MTX), Mycophenolate mofetil(MMF) and antithymocyle globulin(ATG). When GVHD developed, methylprednisolone(MP) was given at first, if the response was poor, anti-CD25 antibody was given to the recipients as quickly as possible and CSA was replaced with tacrolimus. 20 patients achieved sustained, full-donor-type engraftment. the HLA-Cw matched group and mismatched group attained successful neutrophil recovery at a median of 12 days and 13 days, recovery of platelet counts of more than 20×109/L was observed at a median of 20 days and 23 days. Between the two groups were no differences in engraftment. The cumulative incidence of grades II-IV acute GVHD were 77% in HLA-Cw matched group and 14.3% in HLA-Cw mismatched group(P<0.05). 36 months disease-free survival probabilities was 46.2% in HLA-Cw matched group, 28 months disease-free survival probabilities was 85.7% in HLA-Cw mismatched group. The Karnofsky clinical performance status of survival patients was over 90%. In conclusion, HLA-Cw mismatched in donor and receipt of haploidentical SCT was benefited to reducing II–IV aGVHD, and it was in favor of long term survival.