Effect of perioperative autologous versus allogeneic blood transfusion on the immune system in gastric cancer patients

Background： Allogeneic blood transfusion-induced immunomodulation （TRIM） and its adverse effect on the prognosis of patients treated surgically for cancer remain complex and controversial. However, the potential risk associated with allogeneic blood transfusion has heightened interest in the use of autologous blood transfusion. In the present study, the serum concentrations of neopterin, interferon-gamma （IFN-γ）, T lymphocyte subsets （CD3^＋, CD4^＋, CD8^＋, CD4^＋/CD8^＋） and a possible association between these variables were investigated. The purpose was to further evaluate the effect of autologous versus allogeneic blood transfusion on immunological status in patients undergoing surgery for gastric cancer. Methods： Sixty ASA Ⅰ～Ⅱ（American Society of Anesthesiologists） patients undergoing elective radical resection for stomach cancer were randomly allocated to receive either allogeneic blood transfusion （n=30） or autologous blood transfusion （n=30）. Serum concentrations of the neopterin, IFN-γ and T lymphocyte subsets in the recipients were measured before induction of anesthesia, after operation, and on the 5th postoperative day. Results： Both two groups, serum neopterin, IFN-γ, percentages of T-cell subsets （CD3^＋, CD4^＋）, and CD4^＋/CD8^＋ ratio had significantly decreased after operation, but decreased more significantly in group H （receiving allogeneic blood transfusion） than those in group A （receiving autologous whole blood transfusion） （P〈0.05）. On the 5th postoperative day,serum neopterin, IFN-γ, CD3^＋, CD4^＋ T-cells, and CD4^＋/CD8^＋ ratio returned to the baseline values in group A. In contrast, the above remain decreasing in group H, where there were no significant relations between serum neopterin and IFN-γ. Conclusion：Perioperative surgical trauma and stress have an immunosuppressive impact on gastric cancer patients. Allogeneic blood transfusion exacerbates the impaired immune response. Autologous blood transfusion might be significantly beneficial for immune-compromised patients in the perioperative period, clearly showing its superiority over allogeneic blood transfusion.

Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for Patients with Hematologic Malignancies

To investigate the therapeutic effects and associated complications of allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, 40 patients with various malignant hematopoietic diseases received allo-PBSCT. The preparative regimens were based on BUCY2 or modified BUCY2, The acute graft-versus host disease （aGVHD） was prevented by cyclosporin A and shortterm MTX regimen in all patients. Two patients from donors with one fully mismatched HLA on DRB1 locus and 4 from unrelated donor also administered Zenapox （CD25 MAb） at dosage of 1 rag/ kg every day on the day before transplantation and day 4 after transplantation. These 6 patients were also treated with mycophenolate mofetil （MMF）. Transfusion of the donor cells： The median of the transfused nucleated cells was 5.38×10^8/kg and that of the CD34^＋ cells was 7.8×10^6/kg respectively. All the patients gained hematopoietic reconstruction except one who died of infection before engraftment. Seven patients got Ⅱ°-Ⅳ° aGVHD and the incidence was 17.5 %. Fourteen patients got cGVHD and the incidence was 53.8 % in the patients who survived over 6 months. Twenty-eight patients had fever or other characteristics of infection. The median follow-up time was 13.8 months. The incidence of transplantation related mortality （TRM） was 17.5 %and 2 patients relapsed （5.0 %）. It was concluded that allo-PBSCT can reconstruct hematopoiesis quickly and is a favorable therapeutic method for leukemia.

Perioperative anemia management in colorectal cancer patients:A pragmatic approach

Anemia,usually due to iron deficiency,is highly prevalent among patients with colorectal cancer.Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization.Preoperative anemia predicts for decreased survival.Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes,increased post-operative nosocomial infections,longer hospital stays,increased rates of cancer recurrence and perioperative venous thromboembolism.Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management,minimizes or eliminates allogeneic blood transfusion.This includes restrictive transfusion policy,thromboprophylaxis and anemia management to improve outcomes.Normalization of preoperative hemoglobin levels is a World Health Organization recommendation.Iron repletion should be routinely ordered when indicated.Oral iron is poorly tolerated with low adherence based on published evidence.Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions.Serious adverse events with intravenous iron are extremely rare.Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care.Erythropoiesis stimulating agents may improve response rates.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.

Allogeneic peripheral blood stem cell transplantation for leukemia

Objective To observe engraftment kinetics, the incidence and severity of graft-versus-host disease (GVHD), and clinical outcome on 40 recipients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT).Methods From June 1997 to May 1999, forty leukemia patients with a median age of 35 years underwent allo-PBSCT. PBSC were mobilized with G-CSF at a dose of 5 μg/kg s.c. every 12 hours for 5 days. A median of 7.7 (2.0 - 16.8) × 106 CD34+ cells/kg was infused into the recipients. Busulfancyclophosphamide (BU-CY) was used as the conditioning regimen. All patients received cyclosporine A and either methotrexate ( n = 34) or methylprednisolone ( n = 6) for GVHD prophylaxis.Results Engraftment of neutrophils and platelets was achieved at a median of 13 days (9- 28 days) and 12 days (7- 60 days) respectively. Patients receiving ≥4×106 CD34+ cells/kg or given G-CSF post transplant had significantly accelerated neutrophil and platelet engraftment. Acute GVHD occurred in 17 of 40 patients (42.5％), with grade Ⅱ-Ⅳ acute GVHD in 10 patients (25％). Chronic GVHD developed in 21 (9 extensive, 12 limited) out of 30 evaluable patients (21/30, 70％) with a median follow up of 380 days (180-900 days). Transplant related mortality was 17.5％ end the relapse rate was 10％. The probability of leukemia free survival at 3 years was 72.5％.Conclusion Allo-PBSCT can provide rapid hematopoietic reconstitution without an increased incidence of acute GVHD, but may be associated with a high risk of chronic GVHD.

An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n=11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n=9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

Outcomes of peripheral blood stem cell transplantation in patients from human leukocyte antigen matched or mismatched unrelated donors

Background AIIogeneic peripheral blood stem cell transplantation from unrelated donors （UR-PBSCT） is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen （HLA）-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. Methods Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. Results One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor （10/10）, 36 of them with a one locus mismatched donor （9/10）, and 15 of them with a two loci mismatched donor （8/10）. Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups （P〉0.05）. Two-year cumulative incidence of relapse, overall survival （OS） and disease-free survival （DFS） among those three groups were similar （P〉0.05）. The cumulative incidence of 100-day Ill-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group （3.3%, 8.6%, and 26.7%, P=0.009）. The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups （26.67%, 52.78%, and 41.18%, P=0.035）. The cumulative incidence of 100-day and 2-year transplantation related mortality （TRM） in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, （8.4%, 11.8% and 33.3%, P=0.016） and （12.3%, 18.7% and 47.5%, P=0.002）. Conclusions HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM. Chin Med J 2014;127 （14）： 2612-2617