scholarly journals Predictions in the Face of Clinical Reality: HistoCheck versus High-Risk HLA Allele Mismatch Combinations Responsible for Severe Acute Graft-versus-Host Disease

2011 ◽  
Vol 17 (9) ◽  
pp. 1409-1415 ◽  
Author(s):  
Medhat Askar ◽  
Ronald Sobecks ◽  
Yasuo Morishima ◽  
Takakazu Kawase ◽  
Amy Nowacki ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clinical Reality ◽  
The Face ◽  
Acute Graft

Deleterious Roles of the KIR Ligand Mismatch on Acute Graft Versus Host Disease in Unmanipulated HLA-Mismatched/Haploidentical Blood and Marrow Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2874-2874
Author(s):  
Xiao Jun Huang ◽  
Xiang Yu Zhao ◽  
Dai Hong Liu ◽  
Kai Yan Liu ◽  
Lan Ping Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Multivariate Analysis ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Blood And Marrow Transplantation ◽  
Acute Graft

Abstract The beneficial effect of KIR ligand mismatch with a very low incidence of rejection, acute graft versus host disease (aGVHD), and leukemia relapse had been demonstrated by Perugia’s group in the Haploidentical mismatched Hematopoitic cell transplantation (HCT) with extensive T cells depletion in vitro. However, many analytical results of the haploidentical and unrelated mismatched transplantation appeared to be inconsistent with Perugia’s work. The disputes in the inconsistent roles of KIR ligand mismatch seem to be caused by the different transplant protocols with different extent of T cells depletion in vitro or in vivo. In recent years, we successfully established a novel protocol—conditioning including antithymocyte globulin followed by un-manipulated HLA-mismatched/haploidentical blood and marrow transplantation, which can achieve comparable outcomes to HLA-identical sibling transplantation. Following the contradictory results about the KIR ligand mismatch in the haploidentical related and mismatched unrelated HCT, we have evaluated the roles of the KIR ligand mismatch in 94 leukemia patients undergoing unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation. Multivariate analysis showed that both KIR ligand mismatch (HR 2.833, CI, 1.286–6.241, p=0.01) and doses of T cells (HR 3.059, CI, 1.292–7.246, p=0.011) were independent risk factors causing the acute graft versus host disease (aGVHD). In addition, compared to patients without KIR ligand mismatch, KIR ligand mismatch worsened the adverse effect of ‘high’ dose T cells (>1.48×108/kg) on aGVHD (100% vs 63.3%, p=0.036), and increased the incidence of aGVHD in patients with HLA-C mismatch (80% vs 57.4, p=0.056). Since multivariate analysis demonstrated that high risk leukemia is the only predictor for TRM, relapse and OS, we further analyzed the effect of KIR ligand mismatch on prognosis in standard and high risk patients. The differences in TRM (50% vs 7.6%, p=0.005) and OS (50% vs 88.4%, p=0.014) between patients with and without KIR ligand mismatch were most striking for standard risk. Therefore we conclude that due to the presence of large dose T cells in the allograft, the alloreactivity of NK cells had been inhibited and KIR ligand mismatch directed alloreactive T cells played crucial roles in our model.

High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2235-2241 ◽  
Author(s):  
Takakazu Kawase ◽  
Yasuo Morishima ◽  
Keitaro Matsuo ◽  
Koichi Kashiwase ◽  
Hidetoshi Inoko ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Risk ◽  
Molecular Mechanism ◽  
Amino Acid Substitution ◽  
Graft Versus Host Disease ◽  
Hla Class I ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combination is little known, and its molecular mechanism to induce acute graft-versus-host disease (aGVHD) remains to be elucidated. A total of 5210 donor-patient pairs who underwent transplantation through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of the HLA allele mismatch combinations and amino acid substitution positions in 6 HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations (high-risk mismatch) for severe aGVHD were identified, and the number of high-risk mismatches was highly associated with the occurrence of severe aGVHD regardless of the presence of mismatch combinations other than high-risk mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class I were identified as those responsible for severe aGVHD. These findings provide evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule. Furthermore, the identification of high-risk mismatch, that is, nonpermissive mismatch, would be beneficial for the selection of a suitable donor.

scholarly journals Decitabine Containing Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Intermediate- and High-Risk Myelodysplastic Syndrome/Acute Myeloid Leukemia: Potential Decrease in the Incidence of Acute Graft Versus Host Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5647-5647
Author(s):  
Yuan Li ◽  
Qing Ya Wang ◽  
Ze Yin Liang ◽  
Yue Yin ◽  
Wei Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Versus Host Disease ◽  
Conditioning Regimen ◽  
Host Disease ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Relapse Time ◽  
Risk Patients ◽  
Grade Ii ◽  
Acute Graft

Objective: To evaluate the role of Decitabine in the allo-HSCT conditioning regimen for intermediate- and high-risk patients with MDS or AML. Methods:Retrospective analysis of data pertaining to 76 intermediate and high-risk patients with MDS or AML who underwent allo-HSCT between December 2005 and June 2018 at the Peking University First Hospital. Forty patients received Decitabine containing conditioning regimen before transplantation, while thirty-six patients received regimen without Decitabine. Results: Overa median follow up of 40 months(range, 1 to 155), the incidence of grade II to IV acute graft versus host disease was 12.5% in the Decitabine group and 41.7% in the non-Decitabine group (P=0.003). On multivariate analysis, Decitabine containing conditioning regimen was found to protect against grade II to IV aGVHD (HR=0.275, 95% confidence interval 0.098-0.770,P=0.014). Incidence of respiratory infection in the Decitabine and non Decitabine groups was 22.5% and 52.78%, respectively (P=0.012). No significant between group difference was observed with respect to 3-year OS, DFS, or RR (P=0.980, 0.959, and 0.837, respectively), while the median relapse time was longer in the Decitabine group [7 months (range, 2 to 12) versus 3 months (range, 2 to 4), P=0.171]. Decitabine containing conditioning showed a tendency for lower relapse rate among higher risk patients, as assessed by IPSS R; however, the between-group difference was not statistically significant (P=0.085). Conclusions: Inclusionof Decitabine in the conditioning regimen for allo-HSCT in intermediate- and high-risk patients may lower the incidence of aGVHD and respiratory infections, and contribute to longer median relapse time. Disclosures No relevant conflicts of interest to declare.

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