Universal leukoreduction of cellular blood components in 2001? No.
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Blood Component Transfusion↗
Biomedical subjects
L T Goodnough
Publications and source records attributed to L T Goodnough.
Transfusion medicine : support of patients undergoing cardiac surgery.
There is still no alternative that is as effective or as well tolerated as blood; nevertheless, the search for ways to conserve, and even eliminate blood transfusion, continues. Based on hemoglobin levels, practice guidelines for the use of perioperative transfusion of red blood cells in patients undergoing coronary artery bypass grafting have been formulated by the National Institutes of Health and the American Society of Anesthesiologists. However, it has been argued that more physiologic indicators of adequacy of oxygen delivery should be used to assess the need for blood transfusion. Methods used for conserving blood during surgery include autologous blood donation, acute normovolemic hemodilution and intra- and postoperative blood recovery and reinfusion. The guidelines for the use of autologous blood transfusion are controversial and it does not appear to be cost effective compared with allogeneic blood transfusion in patients undergoing cardiac surgery. Similarly, the cost effectiveness of intra- and postoperative blood recovery and reinfusion need further evaluation. Treatment with recombinant human erythropoietin (rhEPO) remains unapproved in the US for patients undergoing cardiac or vascular surgery, but it is a valuable adjunct in Jehovah's Witness patients, for whom blood is unacceptable. The characterization of darbepoetin alfa, a novel erythropoiesis stimulating protein with a 3-fold greater plasma elimination half-life compared with rhEPO, is an important advance in this field. Darbepoetin alfa appears to be effective in treating the anemia in patients with renal failure or cancer and trials in patients with surgical anemia are planned. Desmopressin has been used to effectively reduce intraoperative blood loss. Topical agents to prevent blood loss, such as fibrin glue and fibrin gel, and agents that alter platelet function, such as aspirin (acetylsalicylic acid) or dipyridamole, need further evaluation in patients undergoing cardiac surgery. Aprotinin has been shown to preserve hemostasis and reduce allogeneic blood exposure to a greater extent than the antifibrinolytic agents tranexamic acid and aminocaproic acid. Controlled clinical trials comparing the costs of these agents with clinical outcomes, along with tolerability profiles in patients at risk for substantial perioperative bleeding are needed.
Blood Loss, Surgical↗
Erythropoietin, iron, and erythropoiesis.
Recent knowledge gained regarding the relationship between erythropoietin, iron, and erythropoiesis in patients with blood loss anemia, with or without recombinant human erythropoietin therapy, has implications for patient management. Under conditions of significant blood loss, erythropoietin therapy, or both, iron-restricted erythropoiesis is evident, even in the presence of storage iron and iron oral supplementation. Intravenous iron therapy in renal dialysis patients undergoing erythropoietin therapy can produce hematologic responses with serum ferritin levels up to 400 microg/L, indicating that traditional biochemical markers of storage iron in patients with anemia caused by chronic disease are unhelpful in the assessment of iron status. Newer measurements of erythrocyte and reticulocyte indices using automated counters show promise in the evaluation of iron-restricted erythropoiesis. Assays for serum erythropoietin and the transferrin receptor are valuable tools for clinical research, but their roles in routine clinical practice remain undefined. The availability of safer intravenous iron preparations allows for carefully controlled studies of their value in patients undergoing erythropoietin therapy or experiencing blood loss, or both.
Animals↗
Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor-mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation.
The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF-mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute neutrophil count (ANC) increments. However, the effect of leukocyte compatibility on outcomes with G-CSF-mobilized granulocyte transfusions is unclear. The objectives were to determine the effect of leukocyte compatibility on ANC increments and selected clinical outcomes after transfusion of prophylactic, G-CSF-mobilized granulocyte components into neutropenic recipients of autologous peripheral blood stem cell (PBSC) transplants. Beginning on transplant day 2, 23 evaluable recipients were scheduled to receive 4 alternate-day transfusions of granulocyte components apheresed from a single donor given G-CSF. G-CSF was also given to recipients after transplantation. Recipient ANC was determined before and sequentially after each granulocyte transfusion to determine the peak ANC increment. Leukocyte compatibility was determined at study entry only by a lymphocytotoxicity screening assay (s-LCA) against a panel of HLA-defined cells. Eight recipients had positive s-LCA. On days 2 and 4, the mean peak ANC increments after granulocyte transfusion were comparable between the cohorts with positive and negative s-LCA. However, the mean peak ANC increments on day 6 (246/microL vs 724/microL; P =.05) and day 8 (283/microL vs 1079/microL; P =.06) were lower in the cohort with positive s-LCA, in spite of the transfusion of comparable component cell doses. Adverse reactions occurred with only 5 of 87 (5.7%) granulocyte transfusions and were not associated with leukocyte compatibility test results. Platelet increments, determined 1 hour after granulocyte transfusion, were comparable between the cohorts. Although the 2 cohorts received PBSC components with similar CD34(+) cell doses, the cohort with a positive s-LCA had delayed neutrophil engraftment and a greater number of febrile days and required more days of intravenous antibiotics and platelet transfusions. Leukocyte incompatibility adversely affected ANC increments after the transfusion of G-CSF-mobilized granulocyte components and clinical outcomes after PBSC transplantation.
ABO Blood-Group System↗
Management approaches to platelet-related microvascular bleeding in cardiothoracic surgery.
Patients undergoing cardiac surgery with cardiopulmonary bypass are at increased risk for microvascular bleeding that requires perioperative transfusion of blood components. Platelet-related defects have been shown to be the most important hemostatic abnormality in this setting. The exact association between preoperative use of potent platelet inhibitors and either bleeding or transfusion in patients undergoing cardiac surgical procedures is currently being defined. Laboratory evaluation of platelets and coagulation factors can facilitate the optimal administration of pharmacologic and transfusion-based therapy. However, their turnaround time makes laboratory-based methods impractical for concurrent management of surgical patients, which has led many investigators to study the role of point-of-care coagulation tests in this setting. Use of point-of-care tests of hemostatic function can optimize the management of excessive bleeding and reduce transfusion. Accordingly, point-of-care tests that assess platelet function may also identify patients at risk for acquired, platelet-related bleeding. The ability to reduce the unnecessary use of blood products and to decrease operative time or reexploration rates has important consequences for blood inventory, blood costs, and overall health care costs.
Blood Coagulation Factors↗
Innovations in allogeneic stem-cell transplantation.
Allogeneic bone marrow transplantation (BMT) is associated with prolonged periods of neutropenia and thrombocytopenia, which can lead to severe infections and bleeding complications. Transplantation-related side effects might be ameliorated by use of cytokine-mobilized peripheral blood progenitor cells (PBPC) Instead of bone marrow. We have studied PBPC mobilization and transplantation in more than 150 patients with high-risk hematologic malignancies. Normal donors can be sufficiently mobilized with granulocyte colony-stimulating factor (G-CSF), with 91% of G-CSF-stimulated normal donors producing more than 2 x 10(6) CD34+ cells/kg by a single apheresis. The combination of G-CSF plus granulocyte-macrophage colony-stimulating factor (GM-CSF) was more effective than mobilization with G-CSF alone. A clear relationship was seen between numbers of resting CD34+ cells premobilization and numbers of PBPC collected by apheresis, indicating that resting CD34+ cells might be used to predict mobilization results and identify donors who could benefit from more effective mobilization regimens. Transplantation of G-CSF-mobilized PBPC was associated with a more rapid engraftment than that observed for BMT. While engraftment was safe and acute graft-versus-host disease (aGvHD) rates were not increased over BMT, chronic GvHD rates were higher after PBPC transplantation. An additional PBPC infusion on day +3 resulted in a further shortening of neutropenia and thrombocytopenia. Incorporation of these innovative approaches with "minimal" conditioning regimens has resulted in near-complete elimination of fever, neutropenia, thrombocytopenia, and the need for antibiotics and RBC and platelet transfusions after allogeneic transplantation.
Animals↗
Does early treatment with high-dose methylprednisolone alter the course of hepatic regimen-related toxicity?
Hepatic regimen-related toxicity (RRT) is a serious complication of stem cell transplantation. Cytokine activation may be involved in the pathogenesis. Corticosteroids are potent inhibitors of cytokine production, and, therefore could play a role in the treatment of hepatic RRT. Between January 1994 and June 1998, 28 of 782 consecutive transplant patients (3.6%) developed hepatic RRT (20 veno-occlusive disease (VOD) and eight liver dysfunction of uncertain etiology (LDUE) as defined by Seattle criteria), and were treated with high-dose methylprednisolone (MP, 500 mg/m2 i.v. every 12 h for six doses), initiated upon increase in serum total bilirubin to > or =4 mg/dl. Other causes of liver dysfunction were excluded. Response to therapy with high-dose MP was defined as reduction in total bilirubin by 50% within 10 days of initiation of MP. Overall, 17 patients (61%) responded to treatment (12 patients with VOD, five patients with LDUE). The bilirubin in responding patients decreased from a mean of 8.6 mg/dl (range, 4-17.9) at the start of MP to 4.1 mg/dl (range, 0.5-17.9) 10 days later. There were no statistically significant differences between responders and non-responders in the day treatment with high-dose MP was initiated (P = 0.38), total serum bilirubin (P = 0.17) and percent weight gain at the time high-dose MP was started (P = 0.10) or the calculated probability of fatal outcome from VOD (18% for responders, 23% for non-responders; P = 0.30). A lower pre-transplant DLCOc was observed among non-responders (P = 0.04). At 100 days post-transplant, hepatic RRT resolved in all 13 survivors who responded to high-dose MP, and in one non-responding patient. No serious toxicities due to high-dose MP were observed. We conclude that resolution of hepatic RRT occurred in the majority of patients treated with high-dose MP in this study; however, randomized controlled trials are required to determine the efficacy of high-dose MP for treatment of hepatic RRT.
Adult↗
Adverse side-effects associated with G-CSF in patients with chronic myeloid leukemia undergoing allogeneic peripheral blood stem cell transplantation.
Administration of the myeloid growth factor G-CSF after allogeneic hematopoietic stem cell transplantation is usually well tolerated, and associated with rapid hematopoietic engraftment. We report a high incidence (50%) of side-effects associated with post-transplant G-CSF in patients with chronic phase chronic myeloid leukemia undergoing allogeneic HLA-identical sibling peripheral blood stem cell transplantation. One or more of the following signs and symptoms were observed shortly after the subcutaneous injection of G-CSF: dyspnea, chest pain, nausea, hypoxemia, diaphoresis, anaphylaxis, syncope and flushing. These reactions led to discontinuation of G-CSF in the majority of patients. Predictive factors could not be identified, and the underlying mechanism leading to these reactions is unknown.
Adult↗
Allogeneic peripheral blood stem cell transplantation following CD34+ enrichment by density gradient separation.
GVHD is a significant cause of morbidity and mortality following allogeneic peripheral blood stem cell transplantation (AlloPBSC). CD34+ cell selection could reduce GVHD by negative selection of T cells. In an attempt to reduce the T cell content of alloPBSC we carried out a trial in which 11 patients with hematologic malignancies received alloPBSC from HLA-matched siblings following density gradient separation using an isotonic colloidal silica solution (BDS 60; Dendreon Corporation). Cyclosporine and methylprednisone were used for GVHD prophylaxis. The mean yield of CD34+ cells was 69 +/- 15.6% with a purity of 2.9 +/- 1.7%. The mean number of CD3+ cells infused was 1.0 +/- 1.2 x 107/kg, representing a 1.3 log depletion. A high risk of acute GVHD was observed: grade II-IV in 7/11 (64%) and grade III-IV GVHD in 5/11 (45%) patients. Nine of the 11 (82%) patients died with a median survival of 68 days. Cytokine expression in PBSC was compared pre and post processing. Interferon-gamma was detected only following density gradient separation while IL-8 expression increased 3- to 6-fold post processing. Therefore, processing with this device may augment production of pro-inflammatory cytokines. Bone Marrow Transplantation (2000) 25, 1223-1228.
Antigens, CD34↗
Outcomes of high-dose chemotherapy and autologous stem cell transplant in isolated locally recurrent breast cancer: a multicenter evaluation.
To determine the outcomes of women with isolated loco-regional recurrence (LRR) of breast cancer treated with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) following conventional therapy, we conducted a retrospective review of 58 patients from five institutions treated between 1990 and 1998. Forty-five patients (78%) had > or = 2 poor prognostic factors (PPF) (defined as disease-free interval preceding LRR < or = 2 years, hormone receptor negative/refractory disease, and incomplete resection). At median follow-up of 14.2 (0.5-72) months, 36 patients (62%) developed progressive disease. Disease progression usually occurred at local (27 patients) vs distant (nine patients) sites. Median time to disease progression following ASCT was 6.1 (1.3-31.4) months. At last follow-up, 23 patients (40%) had expired (all due to disease progression), and 13 (22%) were alive with, and 22 (38%) without progressive disease. By Kaplan-Meier analysis, the estimated median PFS and OS was 20.3 and 29.2 months, respectively. In a multivariate model, complete remission at time of HDCT and estrogen-receptor positive disease were predictive of significantly longer PFS and OS. The survival of this cohort was similar to previous reports of those treated with conventional therapy alone, and to those with distant metastases treated with HDCT. Frequent progression locally, suggests that strategies to improve local disease control are needed.
Adult↗
Resolution of psoriasis after allogeneic bone marrow transplantation for chronic myelogenous leukemia: late complications of therapy.
Treatment of autoimmune disease with bone marrow transplantation (BMT) is under investigation. A few reports of patients undergoing allogeneic BMT for malignant conditions observed the resolution of psoriasis after BMT, with minimal late morbidity. We describe a patient with chronic myelogenous leukemia (CML) whose psoriasis resolved completely after allogeneic BMT. However, the patient's course was complicated by extensive chronic graft-versus-host disease (GVHD), recurrent serious infections, poor performance status and quality of life, and severe disability. The patient died 887 days post transplant due to infectious complications. The potential benefits and risks of treatment of autoimmune diseases with allogeneic BMT are discussed.
Autoimmune Diseases↗
Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, double-blind trial.
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Double-Blind Method↗
A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty.
BACKGROUND: The value of acute normovolemic hemodilution (ANH) as compared to preoperative autologous blood donation (PABD) in orthopedic surgery is unknown. Therefore, a prospective, randomized study was conducted to compare these techniques in patients undergoing primary total hip arthroplasty. STUDY DESIGN AND METHODS: ANH patients underwent phlebotomy for up to 3 units, or to a target Hct level of 28 percent after induction of anesthesia. PABD patients were asked to donate up to 3 units before admission. RESULTS: Mean baseline Hct levels were not different in ANH and PABD patients (39. 7 +/- 4.5 vs. 41.8 +/- 3.8%, p = 0.09). No difference was found in allogeneic blood exposure among ANH and PABD cohorts: 4 (17%) of 23 ANH patients received a total of 9 allogeneic blood units, compared to no allogeneic transfusions in the PABD cohort (p = 0.30). Total blood costs associated with ANH were significantly (p<0.05) lower than blood costs associated with PABD ($151 +/- 154 vs. $680 +/- 253, respectively). CONCLUSION: In patients undergoing total hip arthroplasty, ANH is safe, can be considered equivalent to PABD in effectively reducing exposure to allogeneic RBCs, and is less costly than PABD.
Adult↗
The case against universal WBC reduction (and for the practice of evidence-based medicine).
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Blood Component Removal↗
Blood conservation in patients undergoing non-cardiac surgery.
Concerns about the safety, inventory, and cost of allogeneic blood have led to a renewed interest in blood conservation. Autologous blood collection techniques, including preoperative autologous donation, acute normovolemic hemodilution, and perioperative blood recovery are routinely used as alternatives to allogeneic transfusion. In the future, these techniques may be combined with pharmacological strategies, such as presurgical erythropoietin therapy or red cell substitutes, to reduce further the need for allogeneic blood.
Journal Article↗
Transfusion medicine. Second of two parts--blood conservation.
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Blood Component Transfusion↗
Transfusion medicine. First of two parts--blood transfusion.
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Blood Donors↗
Optimal management of bleeding and transfusion in patients undergoing cardiac surgery.
Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Point-of-care evaluation of platelets, coagulation factors, and fibrinogen can enable physicians to rapidly assess bleeding abnormalities, facilitate the optimal administration of pharmacological and transfusion-based therapy, and also identify patients with surgical bleeding. The ability to reduce the unnecessary use of blood products in this setting has important implications for emerging issues in blood inventory and blood costs. The ability to decrease surgical time, along with exploration rates, has important consequences for health care costs in an increasingly managed health care environment.
Algorithms↗