Perioperative blood transfusion and colorectal cancer recurrence.
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Colorectal Neoplasms↗
Biomedical subjects
J M Heal
Publications and source records attributed to J M Heal.
Leukocyte-reduced transfusions of ABO-identical platelets and clinical outcome in autologous bone marrow transplantation for lymphoma.
In observational studies, use of ABO-identical platelets and leukocyte-reduced blood components have been associated with prolonged survival and reduced morbidity in acute leukemia. We present an analysis of the clinical results of instituting a policy of ABO-identical, leukoreduced transfusions in adult patients with lymphoma undergoing autologous bone marrow transplantation. Consecutive patients with Hodgkin's disease or non-Hodgkin's lymphoma were treated with a BEAC conditioning regimen. The use of ABO-identical platelets and leukoreduction of blood components was associated with reductions in mean number of days with fever > or = 38.5 degrees C (17 vs 10), number of days of antibiotics (34 vs 22) and numbers of days until recovery of neutrophil count > or = 500 x 10(6)/l (26 vs 18). Use of leukoreduced transfusions was the only statistically significant treatment factor predicting more rapid neutrophil engraftment. No significant difference in event-free or overall survival was observed. The differences in morbidity were not explained by variations in supportive care such as use of hematopoietic growth factors, use of peripheral blood stem cells or by any measures of pretransplant disease extent or severity. While conclusions based on cohort studies must be viewed conservatively, these data are consonant with observations from previous animal models and clinical studies. ABO-identical platelet transfusions and leuko-reduction are associated with reduced morbidity in patients undergoing autologous bone marrow transplantation for lymphoma.
ABO Blood-Group System↗
Effects of transfusion on immune function. Cancer recurrence and infection.
The paradigm related to the immunologic consequences of allogeneic blood transfusions has been extended from humoral allosensitization to the effects of transfusion on cellular immune function. This includes downregulation of effector cells, activation of latent viral infection, and the prolonged circulation of donor immunocompetent cells, as seen in graft-vs-host disease. There are now extensive data showing conclusively that allogeneic transfusions are associated with increases in cancer recurrence rates (80% in colorectal cancer) and postoperative bacterial infections (as much as 200% to 1000% in some studies). Whether these associations are causal or not remains in doubt. Based on animal and clinical studies, we believe these associations are likely, in part, due to immune dysregulation caused by transfusion, perhaps augmented by the effects of hemorrhage, anesthesia, and surgical stress. The most likely mechanism underlying transfusion-induced immunosuppression is anergy due to presentation of large amounts of antigen through the intravenous route. This favors presentation of antigen by "nonprofessional" antigen-presenting cells, a situation that usually leads to anergy or tolerance rather than immune activation. Two additional hypothetical mechanisms proposed for immune dysregulation after allogeneic transfusion are (1) prolonged circulation of donor cells causing subclinical graft-vs-host disease, and (2) reactivation of immunosuppressive viruses latently present in recipient white blood cells. Results of some initial interventional studies, employing autologous transfusions or removing white blood cells from allogenic donor blood suggest that relatively simple, cost-effective strategies to ameliorate these complications may be at hand.
Bacterial Infections↗
Blood transfusions and prognosis in colorectal cancer.
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Blood Transfusion, Autologous↗
ABO and platelet transfusion revisited.
Historically, ABO compatibility between donor and recipient has been considered of minor importance for platelet transfusion. However, in a recent randomized trial we showed that provision of only ABO-identical platelets was associated with a significantly higher corrected count increment (CCI) in the early transfusions and with a twofold reduction in refractoriness, as compared with platelets given unmatched for ABO. In older studies this phenomenon was not observed. We wondered whether in these previous studies the use of the conventional term "ABO compatible", whereby ABO-identical platelet transfusions are grouped with those that are merely ABO compatible, might have obscured the advantages of the ABO-identical platelets. In this paper the CCI from our original study are compared with what would have been found had the conventional terminology of "ABO compatible" and "ABO incompatible" been used. In our original study the mean CCI in patients receiving only ABO-identical platelets was 64% higher than that achieved with ABO-unmatched products. However, when the transfusions were reanalyzed according to conventional terminology of ABO "compatible" and "incompatible," the actual benefits of ABO-identical platelets were no longer detected. Thus, had we used the conventional terminology in the original study we would have come to completely different conclusions about the importance of ABO in platelet transfusion. We hypothesize that transfusion of ABO-incompatible plasma leads to the formation of immune complexes that can destroy compatible platelets by indirect mechanisms. This model predicts that the success of a transfusion could be affected by previous incompatible transfusions. When transfusions were classified as to whether they were first, second, or third unmatched transfusion, increasing numbers of transfusions of ABO-incompatible plasma were associated with progressively poorer mean increments. The same was true for platelet ABO-incompatible transfusions. In contrast, increasing numbers of ABO-identical transfusions were not associated with poorer increments. The failure to appreciate that (a) transfusions containing ABO-incompatible plasma yield poor increments and (b) the effects of ABO-nonidentical transfusions are cumulative, and therefore affect the success of subsequent identical transfusions, may have led in the past to the incorrect conclusion that ABO matching was of minor importance in repetitively transfused patients.
ABO Blood-Group System↗
Circulating immune complexes involving the ABO system after platelet transfusion.
It has been proposed that when ABO unmatched platelets are transfused circulating immune complexes (CIC) may be formed between the patient's soluble ABH antigens and the transfused antibodies. Platelets might then be destroyed by bystander mechanisms or by the binding of CIC to the Fc receptor or to C3 binding membrane proteins on the platelet. An ELISA C1q assay was used to detect CIC in 40 patients with haematological diseases who had received multiple platelet transfusions. A significantly larger number of refractory patients were positive (41%) in the assay than non-refractory patients (13%) or normal blood donors (0%). The presence of circulating IgG anti-A was sought in six group A refractory patients who had been transfused with ABO unmatched platelets. To determine whether the IgG anti-A was monomeric or in high molecular weight complexes, the serum was fractionated by gel exclusion chromatography and fractions were tested for the presence of IgG anti-A. In all six patients the peak of IgG anti-A binding occurred in fractions of high molecular weight (200-900 kD). Five out of six patients also demonstrated anti-A activity in fractions corresponding to monomeric IgG (about 150-180 kD). Fractions containing high molecular weight anti-A were purified using a protein G column and the eluates were tested for the presence of group A antigen using dot immunoblotting. Group A antigen was associated with the purified IgG anti-A in 4/5 patients tested. Appropriate transfused and non-transfused controls had no anti-A in any fractions. Although not unexpected, these studies demonstrate for the first time that refractory patients receiving ABO unmatched platelets have CIC composed of ABO antigens and their corresponding antibodies present in their serum that circulate for at least several days. It also confirms the hypothesis that some CIC in haematological patients are induced by transfusion.
ABO Blood-Group System↗
The role of ABO matching in platelet transfusion.
A prospective controlled trial was performed to determine whether the use of ABO-identical platelets from the start of treatment might provide higher post-transfusion platelet increments, reduce the number of platelet transfusions and ultimately delay the onset of refractoriness. Forty newly diagnosed patients with haematological diseases were randomized to receive either pooled ABO-identical platelets or pooled platelets unmatched for ABO group throughout their course. The corrected platelet count increments (CCI) were calculated for the first 25 transfusions of each patient and non-immune factors present at the time of each platelet transfusion were documented. The mean CCI for the first 25 transfusions in the ABO-identical group was significantly higher (6600 +/- 7900 SD) than that achieved with ABO unmatched platelets (5200 +/- 7900; p < 0.01). The effect was most marked for the first 10 transfusions for each patient where the CCI was 64% higher in the ABO-identical group (8200 +/- 7500 vs 5000 +/- 8100; p < 0.0002). Patients given ABO-identical platelets required only about half as many transfusions in the first 30 days (10 versus 17, p < 0.05) or during the first admission (11 versus 21 p < 0.01) as patients in the ABO-unmatched group. A smaller percentage of patients in the ABO-identical group became refractory (36% vs 75% p < 0.03). The data suggest that patients requiring long-term platelet support should be transfused with ABO-identical platelets.
ABO Blood-Group System↗
Treatment of relapsed or refractory Hodgkin disease and non-Hodgkin lymphoma with high-dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue.
Nine patients with relapsed or refractory Hodgkin disease or non-Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 x 10(9)/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days posttransplant. Two patients died of transplant-related complications and one relapsed 250 days post-transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution. Although administration of cytotoxic therapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive "salvage" therapy. Additional follow-up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants.
Adult↗
Selection of platelets for refractory patients by HLA matching and prospective crossmatching.
A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.
Adult↗
White cell reduction, ultraviolet irradiation, and platelet refractoriness in acute myeloid leukemia.
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ABO Blood-Group System↗
Antibodies to plasma proteins: an association with platelet transfusion refractoriness.
We hypothesized that antibodies to HLA-linked polymorphic plasma proteins could be involved in platelet refractoriness by an 'innocent bystander' or immune complex mechanism. Employing a kinetic enzyme-linked immunosorbent assay (ELISA) technique the ability of IgG from the plasma of refractory patients to bind to albumin, fibrinogen, complement components C2 and C4 was measured. As compared with controls a high percentage of refractory patients had increased IgG capable of binding to all four plasma proteins: C2 (83%), C4 (83%), albumin (75%), fibrinogen (34%). In the presence of exogenous plasma proteins these antibodies mediated increased deposition of IgG onto normal donor platelets. The plasma protein binding IgG consisted both of monomeric IgG and a broad range of high molecular weight complexes. IgG anti-plasma protein antibody could be eluted from platelets of refractory patients. The development of anti-plasma protein IgG was studied during the course of platelet transfusion therapy and found to increase progressively so that by the 20th transfusion greater than 90% of samples were positive. The presence of plasma protein binding activity correlated with the development of increased levels of platelet bound IgG and refractoriness. Multiple platelet transfusions lead to sensitization to polymorphic determinants on C2 and C4 as well as the formation of high molecular weight complexes. These antibodies and complexes contribute to the deposition of IgG on platelets and may contribute to refractoriness.
Albumins↗
Response to plasma exchange and splenectomy in thrombotic thrombocytopenic purpura. A 10-year experience at a single institution.
BACKGROUND: This study was designed to assess the response of patients with thrombotic thrombocytopenic purpura to plasma exchange and to evaluate the role of splenectomy after relapse. METHODS: The records of all patients with thrombotic thrombocytopenic purpura who had plasma exchange as primary treatment at a single center during a 10-year period were retrospectively reviewed. Response to the initial course of plasma exchange was determined, and the clinical outcome was evaluated in patients whose conditions were either refractory to exchange, responded without relapse, or relapsed after initial response. The outcome of patients treated during relapse with splenectomy was evaluated. A literature review was conducted to determine the clinical outcome in patients treated similarly. RESULTS: Twenty-seven patients for whom data could be evaluated had been treated in the 10-year period. Twenty-one (78%) responded to the plasma exchange, but the conditions of six (22%) were refractory and these patients died. Eight patients (30%) had one or multiple relapses after initial response but had prolonged remissions after additional plasma exchange alone (two patients) or splenectomy (six patients). A review of 19 reports, including 224 patients with thrombotic thrombocytopenic purpura initially treated with plasma exchange, revealed similar findings, with initial response in 81%, refractoriness in 19%, and relapse after initial response in 27% of patients. CONCLUSION: Response to plasma exchange in thrombotic thrombocytopenic purpura is associated with an excellent prognosis, and most deaths occur in patients whose conditions are refractory. Relapses after initial response are frequent but can be managed successfully with additional plasma exchange or with splenectomy, which often induces long-term remissions.
Adult↗
Do white cells in stored blood components reduce the likelihood of posttransfusion bacterial sepsis?
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Blood Preservation↗
Transfusion-induced immunomodulation and its clinical consequences.
The bulk of experimental and clinical data support the theory that homologous transfusion causes significant down-regulation of immunologic functions in a number of settings. These changes in immune function may account for the beneficial associations of transfusion with increased renal allograft survival, and decreased recurrence in Crohn's disease. Conversely, these transfusion-induced effects may be responsible in part for the deleterious association of homologous transfusion with increased cancer recurrence, and increased posttransfusion bacterial and viral infection rates. Host defenses against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood, but the circumstances under which this occurs need to be better defined. Likewise, the hypothesis that modification of blood components to contain fewer leukocytes or less plasma might ameliorate these effects is attractive, but little or no data exist to support or refute it. Future clinical studies will no doubt address these issues.
Blood Transfusion↗
The relationship of blood transfusion, tumor staging, and cancer recurrence.
Previous research demonstrated a relationship between transfusions of whole blood, or large numbers of red cell concentrates, and later recurrence of cancers of the colon, rectum, cervix, and prostate. It is possible that the transfusion of whole blood may represent a surrogate marker for advanced or more aggressive clinical disease. The relationship of clinical or histologic tumor stage, blood transfusion status, and disease outcome was studied in detail. Patients receiving no transfusions or small numbers of red cells (less than or equal to 3 units) had uniformly better recurrence and survival experiences than patients receiving similar amounts of blood that included at least 1 unit of whole blood, regardless of the patient's clinical or histologic tumor stage. In multivariate analyses, stage was an independent predictor of outcome, and transfusion status was not a surrogate marker for stage. The effects on recurrence of stage and transfusion appear to be cumulative. These results are consistent with but do not prove the hypothesis that the transfusion of large amounts of stored plasma and cellular debris impairs the host defenses against cancer, regardless of the underlying biologic and clinical aggressiveness of the cancer.
Blood Transfusion↗
Association of transfusion with postoperative bacterial infection.
Homologous blood transfusion has been implicated as a modulator of the host immune system in a number of clinical settings. Improved renal allograft survival is observed in patients receiving pretransplant transfusions. Decreased recurrence of active inflammatory bowel disease has been recently reported in transfused patients with Crohn's disease. Conversely, deleterious immunomodulatory effects of transfusion may explain the association between transfusion and increased susceptibility to cancer recurrence and bacterial and viral infection. Clinical studies regarding cancer recurrence and transfusion are retrospective and conflicting. There is epidemiologic evidence for more rapid progression of HIV-1 infection in heavily transfused patients. Studies on transfused surgical patients have shown transfusion to be associated with an increased frequency of postoperative bacterial infections. Some studies have come to different conclusions. These investigators have suggested that transfusion may represent a surrogate marker for other risk factors for infection. Animal models designed to control for confounding factors have supported an association between transfusion and bacterial infection severity in most, but not all, reports. Attempts to define the immunologic alterations associated with transfusion have revealed a generalized impairment of cellular immunity in both humans and animals. Although the preponderance of data supports an association between perioperative transfusion and increased susceptibility to postoperative bacterial infection, it is not certain to what extent this relationship constitutes cause and effect.
Animals↗
Growth of gram-positive and gram-negative bacteria in platelet concentrates.
In 1986 the allowable platelet storage time was reduced from 7 to 5 days because of a recent increase in septic deaths associated with platelet transfusion. In this study, the growth curves of two gram-positive and two gram-negative organisms in platelets stored for 7 days in CLX and PL-732 bags were evaluated. Platelets in CLX bags were inoculated with 10(1), 10(2), and 10(3) organisms and 10(2) organisms were introduced into PL-732 bags. Test organisms were inoculated into trypticase soy broth as a control. All four bacteria grew rapidly in trypticase soy broth, reaching 10(9) organisms per mL within 48 hours. In both CLX and PL-732 bags, the growth pattern of gram-positive organisms was generally logarithmic during the first few days of storage. A concentration of 10(8) organisms per mL was present by Day 3 or 4, after which further proliferation was inhibited by the high density of bacteria in the platelets. In PL-732 bags, the proliferation of gram-negative organisms followed a pattern similar to that of the gram-positive bacteria. However, gram-negative organisms grew less well in CLX bags.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Transfusion and recipient immune function.
For some time it has been known that allogeneic blood transfusions have immunologic effects on animal and human recipients. These effects include increased numbers of suppressor T cells, decreased natural killer-cell function, decreased function of macrophages and monocytes, induction of anti-idiotypic antibodies that suppress allogeneic antigen recognition, and decreases in alloreactivity of mononuclear cells in mixed lymphocyte cultures. The meaning of these changes is not clearly understood, nor is the exact clinical importance of these alterations known. However, these decreases in immunologic function may explain a number of clinical consequences some investigators believe are the sequelae of homologous blood transfusions. Clinically important outcomes that are associated with transfusions are improved survival of renal allografts and increased risks of bacterial infection and cancer recurrence after perioperative transfusions. Transfusion of plasma-rich blood components (eg, whole blood) has been specifically associated with earlier cancer recurrence and better renal allograft survival in some patient groups. The new hypothesis that transfusion of stored plasma is a major factor in altering host immune defenses is supported by the observation that patients infected with human immunodeficiency acquired immunodeficiency syndrome more rapidly if they have been transfused with large amounts of plasma. Contrary to previous belief, the transfusion of homologous stored blood plasma may have as great or greater effects on immunity than transfusion of white blood cells. We believe investigation into the immunologic effects of transfusions is likely to have a significant impact on transfusion medicine research and practice over the coming years.
Acquired Immunodeficiency Syndrome↗