For Immediate Release
Contact:
Jami Bitter, Pall Corporation
(516) 484-3600
East Hills, New York -- The results of a study funded by the National Institutes of Health (National Heart, Lung and Blood Institute) which examined three procedures to avoid resistance or rejection to platelet transfusion (alloimmune-mediated platelet refractoriness) found that leukocyte (white blood cell) reduction of platelet components by filtration significantly reduced the incidence of refractoriness. The outcomes of the prospective, multicenter, randomized Trial to Reduce Alloimmunization to Platelets (TRAP), conducted in 530 evaluable patients with acute myeloid leukemia undergoing induction chemotherapy, were published in The New England Journal of Medicine (December 25, 1997).
Reducing exposure to leukocytes resulted in a significantly lower incidence of alloimmune-mediated platelet refractoriness in three groups in which platelets were treated (filtered pooled platelet concentrates [filtered group] 3 percent, Ultraviolet B-irradiated pooled platelet concentrates [UVB-irradiated group] 5 percent and filtered apheresis platelets [filtered apheresis group] 4 percent), compared to the control group (13 percent). The rates of alloimmunization (the detection of lymphocytotoxic antibodies), which are associated with refractoriness, were also significantly lower for the treated groups (filtered group 18 percent, UVB-irradiated group 21 percent and filtered apheresis group 17 percent), compared to the control group (45 percent).
"Alloimmunization and platelet refractoriness are one of the most serious and difficult transfusion therapy hazards to manage," stated Dr. Charles Schiffer, Professor of Medicine and Oncology and Chief of the Division of Hematology/Oncology at the Karmanos Cancer Institute of the Wayne State University of Medicine in Detroit, Michigan, and co-investigator of the TRAP study. "The study has demonstrated that the rate of alloimmunization can be reduced by removing donor leukocytes by filtration, resulting in a higher incidence of acceptance of the transfusion by the patient."
"It was anticipated that our study would demonstrate that filtered apheresis platelets might further reduce the incidence of alloimmunization because of exposure to fewer donors," said Dr. Schiffer. "However, there was no evidence of any added benefit as compared with either filtered or UV B-irradiated (an experimental technique that is not commercially available) pooled platelet concentrates." "Therefore, we now need to question the role of the more expensive platelet products prepared by apheresis in preventing alloimmunization and refractoriness to platelet transfusions."
Alloimmunization and platelet refractoriness
Patients who require repeated platelet transfusions, such as those with acute myeloid leukemia, can become refractory, or reject the transfusion, thereby hindering potentially curative therapy for their condition. Refractoriness occurs when the patients platelet count does not improve after a transfusion. A frequent cause of refractoriness is alloimmunization, where antibodies are formed which, in turn, destroy donor platelets. These antibodies usually result from exposure to "foreign" (non-self) antigens after repeated blood transfusions or from fetal blood that mixes with maternal blood during pregnancy.
Once a patient becomes alloimmunized (has antibodies present), approaches to blunt the antibody response and boost platelet counts, have been both expensive and, in many cases, unsuccessful.
Filtration effective in patients with previous pregnancy and prior transfusions
In women who had a previous pregnancy, the incidence of alloimmune-mediated platelet refractoriness in the treated groups was significantly lower (F-PC group 10 percent, UVB-PC group 17 percent, F-AP group 16 percent ), than in the control group (32 percent). Similarly, the rate of alloimmunization (production of lymphocytotoxic antibodies) was significantly lower in the treated groups (F-PC group 32 percent, UVB-PC group 33 percent, F-AP group 34 percent), than in the control group (62 percent).
"The appreciable reduction in the incidence of alloimmune platelet refractoriness by leukocyte reduction in this study, in both previously pregnant and non-pregnant women and men, represents a significant therapeutic advance," stated Dr. Schiffer.
TRAP study design
The prospective, multicenter, randomized, blinded study, conducted in 530 patients over a 4 year period, was designed to determine whether the use of platelets from which leukocytes had been removed by a filter or had been treated with ultraviolet B irradiation would prevent the formation of antiplatelet antibodies and refractoriness to platelet transfusions.
The study comprised three groups in which platelets were treated and a control group: (1). Leukocyte Filtered Group -- received filtered, pooled random donor platelets (Pall blood filters were used to remove leukocytes); (2). UltraViolet B-Irradiated Group -- received ultraviolet B-irradiated pooled random donor platelets. This is an experimental technology which is not commercially available; (3). Filtered Apheresis Group -- received filtered platelets from individual random donors which reduces patient exposure to antigens of a single donor; (4). Control Group -- received unmodified, pooled random donor platelets. All patients in the study who required concurrent red cell transfusions received leukocyte reduced blood products to limit any further variables in the study.
The primary study endpoint measured was refractoriness to platelet transfusion due to alloimmunization. The study also measured the total incidence of refractoriness to platelet transfusions and positive tests for the presence of two types of antibodies -- lymphocytotoxic antibodies and antibodies against platelet glycoproteins.
Benefits of blood filters
In the study, the TRAP investigators used filters developed by Pall Corporation. Pall leukocyte reduction filters are the products of choice worldwide for most physicians who prescribe leukocyte reduced blood products.
Every year, approximately 500,000 patients receive platelet transfusions. "This study clearly positions filtered platelet concentrate pools as clinically effective and the most cost-effective product of choice in the prevention of alloimmunization and refractoriness to platelet transfusions," said Dr. Barry Wenz, Medical Director of Pall Corporation. He added that, "for patients who receive platelet transfusions, leukocyte reduction by filtration has additional benefits. It can reduce the incidence of febrile transfusion reactions and decrease the risk of infection from viruses harbored by leukocytes, such as cytomegalovirus (CMV)." CMV infection can result in serious infections in patients with impaired immune systems, for example, acute myeloid leukemia, bone marrow transplant and AIDS patients.
Pall Corporation, with annual sales approaching $1 billion, is headquartered in East Hills, New York. The company has the broadest based filtration and separation capabilities in the world. Since 1946, Pall Corporation has demonstrated technological leadership and innovative solutions to complex fluid clarification and purification problems in each of its three major markets - Health Care, Aeropower and Fluid Processing. The company employs 8,500 people at offices throughout the world, with manufacturing facilities in the U.S., Puerto Rico, England and Japan. The company shares are listed on the New York Stock Exchange (PLL), and the London Stock Exchange (0668260).
# # #
Key findings from the TRAP Study (n = 530)
Patient Leukocyte Ultraviolet B Filtered Apheresis
Group Filtered Irradiated (n = 132)
Control (n = 137) (n = 130)
(n = 131)% patients who produced alloantibodies and became refractory to platelet transfusion
13% 3% (P=0.004)* 5% (P=0.03)* 4% (P=0.01)*
% patients refractory to platelet transfusion
16% 7% (P=0.03)* 10% (P=0.17) 8% (P=0.06)
% patients who produced alloantibodies (lymphocytotoxic antibodies)
45% 18% (P<0.001)* 21% (P<0.001)* 17% (P<0.001)*
% patients (women with previous pregnancy) refractory to platelet transfusion
32% 10% (P=0.009)* 17% (P=0.10) 16% (P=0.09)
% patients (women who had been previously pregnant) who produced alloantibodies (lymphocytotoxic antibodies)
62% 32% (P=0.01)* 33% (P=0.02)* 34% (P=0.02)*
% patients who produced antibodies against platelet glycoproteins
11% 6% NS 7% NS 7% NSAdapted from data from the TRAP Study Group. N Engl J Med 1997;37:1861-9.
* Statistically significant compared to the control group
RSS