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Clinical Alert: Periodic Transfusions Lower Stroke Risk in Children with Sickle_cell Anemia Clinical Alert: Periodic Transfusions Lower Stroke Risk in Children with Sickle_cell Anemia National Heart, Lung, and Blood Institute (NHLBI) September 18,1997 Abstract The National Heart, Lung, and Blood Institute today announced that periodic red_blood_cell transfusions in children with sickle_cell anemia has_been found to reduce the rate of stroke in those patients. Findings from a clinical trial made up of 130 children, who ranged in age from 2 to 16, showed that red_blood_cell transfusions every three or four weeks significantly cut the rate of stroke. The study--the Stroke Prevention Trial in Sickle_cell Anemia (STOP)--compared stroke rates in 63 children who received periodic transfusions with 67 children who were getting standard supportive care. The study was based_on clinical observations that showed a decreased risk of stroke in children who already suffered one stroke if hemoglobin S levels were_maintained at or less_than 30%.%The children used in the study were_known to be at high risk for stroke because_of elevated cerebral blood flow, which was_measured by using transcranial doppler screening tests. The STOP trial found that after one year, 10 children in the standard care group had_had a stroke, while only one child in the transfusion group suffered a cerebral_infarction. The results represent a 90%relative decline in the stroke rate. The study, which was_supposed to continue through December 1998, has_been_halted so_that the standard care group could begin receiving the periodic transfusion treatment. The STOP study also confirmed that transcranial doppler screening can be_used to identify children with sickle_cell anemia who are at high risk for a first-time stroke. As a result, it is_recommended now that sickle-cell patients between two and 16 receive transcranial doppler screening. Children with normal screens should be_screened re about every six months. An abnormal screen is a velocity of 200 cm/sec or greater, and should be_elevated on two separate readings. Before screening children with sickle_cell anemia for stroke risk, it is_recommended that screening centers evaluate their TCD equipment and compare it with_that used in the STOP trial. NHLBI contact: Dr. Duane Bonds (301) 435-0055 corrected October 9, 1997 Full Text The National Heart, Lung, and Blood Institute (NHLBI) announced today a treatment that reduces the rate of stroke (cerebral_infarction) in children with sickle_cell anemia. Strokes occur in approximately 10%of children with sickle_cell anemia. These events can be very debilitating, leading to physical and neuropsychological impairment which can affect motor skills, school performance, and overall quality_of_life. The treatment, periodic red_blood_cell transfusions to maintain the level of hemoglobin S (Hbs) below 30, %reduced the rate of cerebral_infarction by 90%in children found to be_increased at risk by virtue of having elevated transcranial doppler velocities. The Stroke Prevention Trial in Sickle_cell Anemia (STOP) proposed to reduce first_time stroke in children with sickle_cell anemia by 70%by the administration of prophylactic transfusion therapy. The study design was based_on the clinical observation that if hemoglobin S (Hbs) levels are_maintained at or below 30%in children who have_had a stroke, the incidence of recurrence can be_reduced from 80%to approximately 10%with periodic exchange or simple transfusions. Between February, 1995 and October, 1996, the NHLBI-sponsored trial, headquartered at the Medical College of Georgia (Dr. Robert Adams) and the New_england Research Institutes (Dr. Donald Brambilla ), enrolled 130 subjects, ages 2 to 16, who had_been found to be at high risk for stroke on the basis of elevated cerebral blood flow measured by transcranial doppler screening tests (greater than or equal_to 200 cm/sec time averaged mean velocities). The patients, drawn from 13 U_s. clinical centers and one in Canada (list attached), were_randomized to receive either standard supportive care or periodic blood_transfusions. The primary endpoint was the comparison of stroke rates in the treated and control groups. The primary analysis of data from the STOP Trial compared stroke rates in 63 children randomized to receive repeated exchange or simple transfusions and 67 children who received standard supportive care. A stroke was_defined as clinically significant neurologic impairment and physical findings, supported by an abnormal magnetic_resonance_imaging (MRI) study. The clinical records and MRI's were_analyzed by a panel that was_blinded to the treatment assignment of the study subjects. The patients in the transfusion arm received simple or exchange transfusions every 3-to-4 weeks in an effort to maintain the Hb S level below 30%.%After one year, 10 of the children in the standard care group had_had a cerebral_infarction, compared with one child in the transfusion group, This difference represents a 90%relative decrease in the stroke rate. The protocol required that red_blood_cell transfusions be_matched for ABO, C, D, E, and K antigens, and the children in both study arms were_followed for signs of alloimmunization, exposure to transfusion-transmitted viral diseases, and iron_overload. Although none of the children in the transfusion arm of the study contracted a transfusion-transmitted virus, 9 developed alloimmunization. Patients in the transfusion group who had_received 250 ml/kg of blood began to develop elevated serum ferritin levels greater than 2500 mg/L and were_started on chelation therapy. The STOP Trial was_scheduled to continue until December, 1998. The results found during interim analyses were so compelling that the study's Data and Safety Monitoring Board, composed of independent, outside experts in the fields of pediatric hematology, neurology, radiology, statistics, and ethics, recommended that the study be_terminated early so_that the children who had_been receiving standard supportive care could be_offered an effective treatment to prevent first_time stroke. On September 2, 1997, the study was_halted, and the investigators in the 14 participating centers were_notified of the results and the efficacy of transfusion therapy. During the past 2 weeks the results were_discussed with the patients in both treatment arms and their parents. The STOP Trial confirmed that TCD can identify children with sickle_cell anemia at high risk for first_time stroke . Since the greatest risk of stroke occurs in early_childhood, it is_recommended that children ages 2-16 receive TCD screening. Screening should be_conducted at a site where clinicians have_been_trained to provide TCDS of comparable quality and information content to those used in the STOP Trial and to read them in a manner consistent with what was_done in STOP. To apply the predictive and therapeutic information developed in the STOP Trial, two abnormal STOP-comparable TCDS are_needed to identify patients at high risk of stroke (velocity greater than 200 cm/sec on two separate occasions. During follow-up, some children in the large screening population, who had_had normal or conditional TCD readings originally, were found to have abnormal TCD readings, indicating that children with normal TCDS should be_screened re at an interval which depends_on their age and the prior result of TCD. Although the optimal timing is_known not, re-screening should occur approximately every 6 months. The TCD equipment used in the STOP Trial was_adapted by Dr. Robert Adams for use in children with sickle_cell disease. It is smaller and less expensive than the TCD currently used in most radiology departments. It is also portable. In_addition it will_not overestimate velocity, and its use will ensure that children will_not be_misclassified as abnormal and unnecessarily transfused. It is_recommended that centers that wish to start screening children with sickle_cell anemia for stroke risk do studies to compare their current equipment with STOP Trial TCD equipment. Dr. Adams should be_contacted for further information and to arrange training. The decision to start a child on chronic blood_transfusion therapy is a clinical decision that should be_made only after careful consideration of the risks and benefits. This decision should be_made in consultation with a physician who has knowledge of the STOP Trial protocol and results and who is_experienced in the safe delivery of blood products, the management of transfusion complications, and the care of the child with sickle_cell anemia. For more information on the STOP Trial, contact Dr. Robert Adams at 706-721-4670 or the Sickle_cell Disease Scientific_research Group Office, NHLBI at 301-435-0055. All STOP Trial performance sites will_be available for patient referrals and for screening children with sickle_cell anemia to ascertain stroke risk and to counsel the patient and parents about treatment options. NHLBI contact: Dr. Duane Bonds (301) 435-0055 corrected October 9, 1997. STOP Principal_investigators: Robert Adams, M_d.,Medical College of Georgia,(706) 721-4670 Donald Brambilla, Ph_d.,New_england Research Institutes ,(617) 923-7747 STOP Clinical Site Directors: Miguel Abboud, M_d.,Pediatric Sickle_cell Program, Children's Hospital, Medical University of South_carolina,(803) 792-2957 Brian Berman , M_d.,Rainbow Babies Children's Hospital,(216) 844-3345. Catherine Driscoll, M_d.,Children's National Medical_center,(202) 884-2867 Bea Files, M_d.,Children's Hospital of Eastern North_carolina,(919) 816-4676 Lewis Hsu, M_d.,Dept. Of Pediatrics, Emory University,(404) 616-3559 Anne Jensen-Hurlet, M_d.,Columbia Presbyterian Hospital,(212) 305-7005 Virgil Mckie, M_d.,Medical College of Georgia,(706) 721-3626 Scott Miller, M_d.,State_university of New_york (718) 270-1692 Nancy Olivieri M_d.,The Hospital for Sick Children (416) 813-6823 Charles Pegelow, M_d.,University of Miami Medical_school,(305) 585-6042 Charles Scher, M_d .,Tulane Medical University,(504) 588-5412 Elliot Vichinsky, M_d.,Children's Hospital of Oakland (510) 428-3651 Winfred Wang, M_d.,St . Jude's Children's Research Hospital (901) 495-3497 Gerald Woods, M_d.,The Children's Mercy Hospital (816) 234-3265 U_s. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894 National_institutes_of_health, Department_of_health & Human Services Copyright, Privacy , Accessibility Last updated: 09 October 1997