IDH mutations occur frequently in Chinese glioma patients and predict longer survival but not response to concomitant chemoradiotherapy in anaplastic gliomas.

Mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) appear to occur frequently and selectively in gliomas. Our aim was to assess whether IDH mutations are common in Chinese glioma patients and whether the mutations predict good response to concomitant chemoradiotherapy. In this study IDH1 and IDH2 mutations were detected in a series of 203 gliomas. IDH1 mutations were present in 75 of the 203 cases (36.9%) while IDH2 mutations in 5 of the 203 cases (2.5%). No tumor was mutated in both IDH1 and IDH2. IDH1/2 mutations were associated with prolonged overall survival in the whole series of patients exclusive of pilocytic astrocytoma (P<0.001), WHO grade Ⅱ patients who received no adjuvant therapy after surgery (P=0.014) and WHO grade Ⅲ patients who received concomitant chemoradiotherapy (standard schedule) after surgery (P=0.033). Furthermore, there was no correlation between IDH1/2 mutations and reponse to concomitant chemoradiotherapy in anaplastic gliomas. Our results suggest that IDH1 mutations also occur freuqently in Chinese glioma patients but the frequency of IDH1 mutations is below the findings reported by North American and European groups. Furthermore, we confirm the prognostic significance of IDH1/2 mutations in gliomas, but the mutations cannot predict a favorable response to concomitant chemoradiotherapy in anaplastic gliomas.

[The outcomes of the thirty patients with refractory leukemia treated with related HLA haploidentical stem cells transplantation].

OBJECTIVE: To assess the outcomes of the therapy for patients with refractory leukemia with HLA haploidentical stem cells transplantation. METHODS: To analyze the outcomes of 30 patients with refractory leukemia who underwent HLA haploidentical peripheral blood stem cells transplantation from August 1998 to August 2004. RESULTS: Thirty refractory leukemia patients including 13 cases of acute non-lymphocytic leukemia, 10 cases of acute lymphocytic leukemia (ALL), 6 cases of chronic myeloid leukemia and 1 case of phase IV non-Hodgkin's lymphoma underwent HLA haploidentical peripheral blood stem cells transplantation. The median age was 25 years old (3-52 years old). Twelve patients received stem cells from parent donors, four from daughter or son donors and the remaining from sibling donors. Three HLA loci mismatched in twelve cases, two HLA loci mismatched in thirteen cases and one HLA locus mismatched in five cases. The conditioning regime consisted of fludara (25 mg/m(2) x 5 d), busulfan (4 mg/kg x 4 d) and cyclophosphamide (60 mg/kg x 2 d). Rabbit anti-human lymphocyte globulin (5 mg/kg x 5 d) was added in some patients in the conditioning regime. A mean of 5.0 (2.9-8.0) x 10(8)/kg mononucleated cells was grafted. The number of mean CD(34)(+) cells was 5.5 (3.0-6.5) x 10(6)/kg. Twenty-seven patients were successfully grafted, one failed to graft, one died from severe fungal infection at day 2 and one died from severe veno-occlusive disease at day 28. The mean time of white cell count more than 1.0 x 10(9)/L was 14 (11-18) days and platelet count more than 20 x 10(9)/L was 15 (11-18) days. ALL the 27 successfully grafted patients got complete remission. Severe acute graft versus host disease occurred in six patients and four of them died. Seven patients suffered from chronic graft versus host disease. Seven patients relapsed and died. The median relapse time was 10 (3-24) months. Fourteen patients are still surviving, and ten have disease free survival. CONCLUSION: It is concluded from our observation that HLA haploidentical peripheral blood stem cells transplantation may be an effective therapy for refractory and relapse leukemia. Some patients with refractory and relapse leukemia treated with HLA haploidentical stem cells transplantation may have disease free survival. Graft versus leukemia effect may be strong in patients receiving HLA haploidentical blood stem cells transplantation and leukemia will probably be relapsed when the patient without complete remission was treated with this therapy.

[Experimental study on NK cells promoting donor marrow engraftment and hematopoietic reconstitution after MHC haploidentical BMT in mice].

OBJECTIVE: To explore the effect of donor-derived NK cells added to pretreatment conditioning regimen on hematopoietic reconstitution after MHC haplotype-mismatched BMT in mice. METHODS: Murine model of MHC haplotype-mismatched BMT was established by using BALB/c(H-2d) x C57BL/6(H-2b) (CB6F(1)(H-2d/b)) mouse as recipient, and C57BL/6(H-2b) mouse as donor. Fifty recipient mice were divided into 5 groups. The mice in the first three groups were each infused 1 x 10(6), 5 x 10(5), 2 x 10(5)/mouse donor-derived NK cells, respectively before TBI ((60)Co, 9.0 Gy) and then conditioned with TBI, followed by infusion of C57BL/6(H-2b) mice bone marrow cells four hours later. The mice in the fourth group received TBI only, and in the fifth group, TBI and BMT at the some doses as the first three groups. Hematopoietic reconstitution, survival time, body weight, histopathology of the recipients were followed up. RESULTS: (1) Survival time was (5.15 +/- 0.66) days for the fourth group, and > 30 days for the other 4 groups. (2) Leukocyte and platelet counts at day 10 after BMT were (0.99 +/- 0.22) x 10(9)/L and (61.0 +/- 7.27) x 10(9)/L respectively for the fifth group and (2.01 +/- 0.21) x 10(9)/L, (101.50 +/- 16.34) x 10(9)/L; (1.98 +/- 0.29) x 10(9)/L, (99.50 +/- 16.41) x 10(9)/L and (1.97 +/- 0.21) x 10(9)/L, (98.0 +/- 16.19) x 10(9)/L for the first three groups, respectively. Histopathology displayed no GVHD in all the groups. CONCLUSION: Donor-derived NK cells could promote hematopoietic reconstitution after MHC haplotype-mismatched BMT in mice.

[Construction of MHC I gene retroviral expression vector and its expression in hematopoietic cells].

OBJECTIVE: To construct the retroviral expression vector of BALB/c mouse H-2Dd gene and study its expression in C57BL/6 mouse hematopoietic cells (MHC). METHODS: A retroviral vector pMSCV encoding H-2Dd gene was transduced into the packaging cell line PT67 by lipofectin, and the hematopoietic cells of C57BL/6(H-2Dd negative) were infected by the above viral supernatant. Reverse transcriptase-polymerase chain reaction and flow cytometry were employed to examine the expression of H-2Dd on the infected cells. RESULTS: The cDNA encoding H-2Dd was correctly inserted into the vector pMSCV, as confirmed by restriction endonuclease digestion. The H-2Dd gene was integrated into the C57BL/6 mouse hematopoietic cell genome and expressed on the cell surface. CONCLUSION: Recombinant H-2Dd of BALB/c mouse retroviral expression vector has been successfully constructed and its expression obtained in C57BL/6 mouse hematopoietic cells, which may facilitate further study of the function of MHC in transplantation immunology.