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A prospective, randomized study of preoperative autologous donation for hip replacement surgery
JOURNAL
CLUB
prior history of intermittent cold hemolytic anemia. She developed a relapse of her disease with a high-titer IgM-k auto red cell antibody. She refused cyclophosphamide therapy and was treated with 4 infusions of 375 mg/m* of rituximab. She went into a prompt remission without side effects. This reportadds to a rapidly growing list of autoimmune illnesses that may’be treatable with rituximab. These include warm and cold autoimmune hemolytic anemia, immune thrombocytopenia, waldenstom’s macroglobulinemia, and cyroglobulinemia. One might wonder whether other devasting B-cell syndromes such as IgM-antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and certain polyneuropathies will prove treatable by this agent. For decades, many of us had seen little other than prednisone and plasmapheresis applied to a whole host of serious illnesses with variable and often marginal effect. Perhaps it is time for these old treatments to stand aside and give this promising new comer a chance. (S.D.) A prospective, randomized study of preoperative autologous donation for hip replacement surgery. D.A. Billofe, S.N. Gbsson, D. Green, eta/. J Bone Joint Surg Am 84:1299-1304, 2002 Although there has been a progressive decline in the use of preoperative autologous blood donation in many circumstances, orthopedic surgery has remained heavily invested in this technique. However, depending on the medical center, the surgeon, the nature of the procedure, and the patient, autologous blood donated preoperatively may often end up discarded. The actual utility of the technique still remains a matter of debate in part because of the lack of diverse randomized controlled trials performed in different practice settings. This study was just such a prospective randomized trial conducted among patients undergoing unilateral primary total hip replacement. Patients scheduled for surgery who had a preoperative hemoglobin > 12 g/dL were randomized either to donate 2 units of autologous blood or not to donate blood. A total of 96 patients completed the study-42 in the autologous arm and 54 in the control arm. The two groups were similar for variables such as age, gender, blood volume, or comorbid features as would be expected by randomization. Estimated surgical blood loss was the same in both groups. The hemoglobin values were similar at baseline. The autologous donors had lower hemoglobin values at admission (12.9 g/dL v 13.8 g/dL) and in the recovery room (10.4 g/dL v 11.5 g/Z). No patient in either group received allogeneic transfusion. Seventy percent of the autologous donors received back their autologous blood. Forty-one percent of the autologous units were discarded unused. The authors concluded that preoperative autologous blood donation provided no benefit for nonanemic patients undergoing primary total hip replacement surgery. To be fair, one might have rephrased their conclusions to say that any benefit (if present) must be so small so as to not be detectable in a study of nearly 100 patients. Thus, any benefit is likely below a 5% mark and importantly 95% of patients are subjected to the inconvenience, cost, and dangers of autologous donation without any benefit. (SD.) Treatment of Epstein-Barr virus positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. T. Haque, GM. Wilkie, C. Taylor, eta/. Lancet360:436-442, 2002.
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Adoptive immunotherapy resulting from transfusion of donor lymphocytes remains very much in its infancy. Nevertheless, steady progress continues to be made and the prospect for therapeutic lymphocyte transfusion continues to look promising. In this report, a team from Scotland and London use donor lymphocytes to treat lymphoproliferative disease caused by Epstein Barr virus (EBV) appearing after o&m transplantation. Because treatment depends on keeping the EBV infection in check and because EBV control depends on T cells, the investigators attempted to reconstitute the patient with T-cell transfusions from partially HLA-matched donors. Although this is not the first time such lymphocyte transfusions have been tried, this study caught my eye because of the unusual nature of the donor material used. Now you must read on. In this phase 1 study, 8 patients with progressive posttransplant lymphoproliferative disease (PTLD) who were not responding to conventional therapy were given from 1 to 6 transfusions of partly HLA-matched allogeneic EBV-specific cytotoxic T cells (CTLs). The CTLs were selected for transfusion from a frozen bank of CTLs derived from healthy blood donors. The frozen bank of donor CTLs was setup at the Scottish national blood transfusion service. The CTLs were grown ex vivo using repeated stimulation with irradiated lymphoblastoid cell lines and recombinant interleukin 2. After expansion, they were tested for the extent of specific activity against EBVbearing target cell lines and then cryopreserved. A frozen bank of expanded CTLs representing common HLA haplotypes found in the United Kingdom developed. Five of the 8 patients completed treatment. Three had a complete remission, and 2 had no response. No graft versus host disease or allospecific antibodies were detected. PTLD tumor response was seen in those with early polyclonal proliferations. EBV load in peripheral blood fell to undetectable levels in all patients who responded to treatment. Although all tumors expressed CD20, only the last 2 of the 8 patients received rituximab. Thus, whether CTL infusions are superior or .-.. inferior to rituximab therapy cannot be addressed by this study. The authors concluded that the response to previously frozen allogeneic CTLs was favorable and that larger studies were needed. They speculated that the widespread development of frozen banks of donor cytotoxic lymphocytes might become a cost-effective form of cellular therapy for patients with EBVmediated PTLD and for patients with other infectious and neoplastic diseases. (SD.)
Increased rate of infection associated with transfusion of old blood after severe injury. P.J. Offner, E.E. Moore, W.L. Biff/, et al. Arch Surg 137:711- 717, 2002. This study adds some fuel to the fire of transfusion-related immune suppression. The authors present evidence suggesting that the age of blood (not the presence of leukocytes) is the culprit leading to increased infections among transfused patients. The study was a prospective cohort study conducted in trauma patients. Sixty-one patients with a high injury score who all received transfusion were studied. The patients received 6 to 20 units of red cells in the first 12 hours of treatment. Major infections were observed in 32 patients (52%). The underlying age and injury severity score was not different among the patients with infection compared with those without
CLUB
prior history of intermittent cold hemolytic anemia. She developed a relapse of her disease with a high-titer IgM-k auto red cell antibody. She refused cyclophosphamide therapy and was treated with 4 infusions of 375 mg/m* of rituximab. She went into a prompt remission without side effects. This reportadds to a rapidly growing list of autoimmune illnesses that may’be treatable with rituximab. These include warm and cold autoimmune hemolytic anemia, immune thrombocytopenia, waldenstom’s macroglobulinemia, and cyroglobulinemia. One might wonder whether other devasting B-cell syndromes such as IgM-antiphospholipid syndrome, thrombotic thrombocytopenic purpura, and certain polyneuropathies will prove treatable by this agent. For decades, many of us had seen little other than prednisone and plasmapheresis applied to a whole host of serious illnesses with variable and often marginal effect. Perhaps it is time for these old treatments to stand aside and give this promising new comer a chance. (S.D.) A prospective, randomized study of preoperative autologous donation for hip replacement surgery. D.A. Billofe, S.N. Gbsson, D. Green, eta/. J Bone Joint Surg Am 84:1299-1304, 2002 Although there has been a progressive decline in the use of preoperative autologous blood donation in many circumstances, orthopedic surgery has remained heavily invested in this technique. However, depending on the medical center, the surgeon, the nature of the procedure, and the patient, autologous blood donated preoperatively may often end up discarded. The actual utility of the technique still remains a matter of debate in part because of the lack of diverse randomized controlled trials performed in different practice settings. This study was just such a prospective randomized trial conducted among patients undergoing unilateral primary total hip replacement. Patients scheduled for surgery who had a preoperative hemoglobin > 12 g/dL were randomized either to donate 2 units of autologous blood or not to donate blood. A total of 96 patients completed the study-42 in the autologous arm and 54 in the control arm. The two groups were similar for variables such as age, gender, blood volume, or comorbid features as would be expected by randomization. Estimated surgical blood loss was the same in both groups. The hemoglobin values were similar at baseline. The autologous donors had lower hemoglobin values at admission (12.9 g/dL v 13.8 g/dL) and in the recovery room (10.4 g/dL v 11.5 g/Z). No patient in either group received allogeneic transfusion. Seventy percent of the autologous donors received back their autologous blood. Forty-one percent of the autologous units were discarded unused. The authors concluded that preoperative autologous blood donation provided no benefit for nonanemic patients undergoing primary total hip replacement surgery. To be fair, one might have rephrased their conclusions to say that any benefit (if present) must be so small so as to not be detectable in a study of nearly 100 patients. Thus, any benefit is likely below a 5% mark and importantly 95% of patients are subjected to the inconvenience, cost, and dangers of autologous donation without any benefit. (SD.) Treatment of Epstein-Barr virus positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. T. Haque, GM. Wilkie, C. Taylor, eta/. Lancet360:436-442, 2002.
167
Adoptive immunotherapy resulting from transfusion of donor lymphocytes remains very much in its infancy. Nevertheless, steady progress continues to be made and the prospect for therapeutic lymphocyte transfusion continues to look promising. In this report, a team from Scotland and London use donor lymphocytes to treat lymphoproliferative disease caused by Epstein Barr virus (EBV) appearing after o&m transplantation. Because treatment depends on keeping the EBV infection in check and because EBV control depends on T cells, the investigators attempted to reconstitute the patient with T-cell transfusions from partially HLA-matched donors. Although this is not the first time such lymphocyte transfusions have been tried, this study caught my eye because of the unusual nature of the donor material used. Now you must read on. In this phase 1 study, 8 patients with progressive posttransplant lymphoproliferative disease (PTLD) who were not responding to conventional therapy were given from 1 to 6 transfusions of partly HLA-matched allogeneic EBV-specific cytotoxic T cells (CTLs). The CTLs were selected for transfusion from a frozen bank of CTLs derived from healthy blood donors. The frozen bank of donor CTLs was setup at the Scottish national blood transfusion service. The CTLs were grown ex vivo using repeated stimulation with irradiated lymphoblastoid cell lines and recombinant interleukin 2. After expansion, they were tested for the extent of specific activity against EBVbearing target cell lines and then cryopreserved. A frozen bank of expanded CTLs representing common HLA haplotypes found in the United Kingdom developed. Five of the 8 patients completed treatment. Three had a complete remission, and 2 had no response. No graft versus host disease or allospecific antibodies were detected. PTLD tumor response was seen in those with early polyclonal proliferations. EBV load in peripheral blood fell to undetectable levels in all patients who responded to treatment. Although all tumors expressed CD20, only the last 2 of the 8 patients received rituximab. Thus, whether CTL infusions are superior or .-.. inferior to rituximab therapy cannot be addressed by this study. The authors concluded that the response to previously frozen allogeneic CTLs was favorable and that larger studies were needed. They speculated that the widespread development of frozen banks of donor cytotoxic lymphocytes might become a cost-effective form of cellular therapy for patients with EBVmediated PTLD and for patients with other infectious and neoplastic diseases. (SD.)
Increased rate of infection associated with transfusion of old blood after severe injury. P.J. Offner, E.E. Moore, W.L. Biff/, et al. Arch Surg 137:711- 717, 2002. This study adds some fuel to the fire of transfusion-related immune suppression. The authors present evidence suggesting that the age of blood (not the presence of leukocytes) is the culprit leading to increased infections among transfused patients. The study was a prospective cohort study conducted in trauma patients. Sixty-one patients with a high injury score who all received transfusion were studied. The patients received 6 to 20 units of red cells in the first 12 hours of treatment. Major infections were observed in 32 patients (52%). The underlying age and injury severity score was not different among the patients with infection compared with those without