Prevention of recurrent hepatitis B infection after liver transplantation

BACKGROUND:Recurrence of hepatitis B virus(HBV) infection after liver transplantation can lead to graft loss and a reduction in long-term survival.The purpose of this review is to summarize the current therapeutic options for preventing HBV recurrence in liver transplant recipients.DATA SOURCES:Up to January 2013,studies that were published in MEDLINE and EMBASE on prevention of HBV recurrence after liver transplantation were reviewed.RESULTS:There have been remarkable advancements in the past two decades on the prevention of HBV recurrence after liver transplantation,from the discovery of hepatitis B immune globulin(HBIG) and lamivudine monotherapy to the combination therapy using HBIG and lamivudine.With the development of newer and stronger antiviral agents,the need for life-long HBIG is doubtful.With their low resistance profile,oral antiviral prophylaxis using these new agents alone is sufficient and is associated with excellent outcome.CONCLUSIONS:Restoration of host HBV immunity with adoptive immunity transfer and vaccination may represent the ultimate strategy to withdraw prophylactic treatment and to achieve a drug free regimen against HBV recurrence after liver transplantation.

Autologous cytokine-induced killer cells combined with chemotherapy in the treatment of advanced colorectal cancer: a randomized control study

Objective：To evaluate the ef icacy of autologous cytokine-induced kil er （CIK） cells transfusion combined with chemotherapy in patients suf ered from advanced colorectal cancer. Methods： Sixty untreated patients with advanced colorectal cancer were randomly divided into two groups. The 30 patients in the control group received chemotherapy with the regimen of xeloda plus oxiplatin （XELOX）. The 30 patients in the trial group were treated with chemotherapy （XELOX） in combination with autologous CIK celltransfusion. T-lymphocyte subgroups were separated and measured by flow cytometry quality of life （QOL） was determined by EORTC QLQ-C30. The short-term curative ef ect was evaluated via imaging examina-tions. The patients’ median progression free survival time was estimated by Kaplan-Meier. Results：The T-lymphocyte im-mune activity was improved in patients received autologous CIK celltransfusion than those treated with chemotherapy alone. The subgroup of CD3＋CD56＋T lymphocyte was significantly increased （4.28 ± 0.45 vs 10.14 ± 1.02, P=0.01）. Short-term ef icacy evaluation revealed that there was no significant dif erence in terms of objective response rate （ORR） between the two groups, but the disease control rate （DCR） was markedly increased （86.7%vs 56.7%, P=0.020） in the group treated by chemotherapy plus CIK cells compared to the group treated with chemotherapy alone. The progression free survival time was 8.64 months （ 95%CI 6.25-9.75 months） in control group and 10.15 months （ 95%CI 7.48-12.52 months） in trial group. Compared to patients in control group, the patients in trial group had significantly longer progression-free survival （P=0.046）. The QOL assessment suggested the QOL in trial group was obviously improved than that in the control group. Compared with the control group, patients treated with autologous CIK celltransfusion scored more in the area of physical function and general health status, while the symptomatic scores in terms of pain, fatigue, nausea and vomiting and diarrhea were significantly reduced. Conclusion：Autologous CIK celltransfusion combined with chemotherapy can ef ectively enhance the immune activity of T-lymphocytes, prevent disease progression and improve the progression-free survival and QOL in patients with advanced colorectal cancer.

Mismatched donor cell infusion-related syndrome following microtransplant in patients with acute myeloid leukemia

Background:Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment,and the concomitant symptoms,including cytokine release syndrome(CRS)or immune-related adverse events(irAEs),are frequently reported.However,clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell(GPBMC)infusion in patients receiving microtransplant(MST)have not yet been well depicted.Methods:We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison.Clinical symptoms and their correlation with clinical features,laboratory findings,and clinical response were explored.Results:Fever(58.0%[51/88])and chills(43.2%[38/88])were the significant early-onset symptoms after GPBMC infusion.Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills(3[2–5]loci vs.5[3–5]loci,P=0.043 and 66.7%[12/18]vs.37.1%[26/70],P=0.024).On the other hand,those with decreased CD4^(+)/CD8^(+)T-cell ratio developed more fever(0.8[0.7–1.2]vs.1.4[1.1–2.2],P=0.007).Multivariable analysis demonstrated that younger patients experienced more fever(odds ratio[OR]=0.963,95%confidence interval[CI]:0.932–0.995,P=0.022),while patients with younger donors experienced more chills(OR=0.915,95%CI:0.859–0.975,P=0.006).Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion,which indicated mild and transient inflammatory response.Although no predictive value of infusion-related syndrome to leukemia burden change was found,the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.Conclusions:Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes,which were associated with donor-or recipient-derived risk factors,with less safety and tolerance concerns than reported CRS or irAEs.