National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell Disease
2008; American College of Physicians; Volume: 148; Issue: 12 Linguagem: Inglês
10.7326/0003-4819-148-12-200806170-00220
ISSN1539-3704
AutoresOtis W. Brawley, Llewellyn J. Cornelius, Linda Edwards, Vanessa Northington Gamble, Bettye L. Green, Charles E. Inturrisi, Allison James, Danielle Laraque, Magda D. Mendez, Carolyn Montoya, Brad H. Pollock, Lawrence R. Robinson, Aaron P. Scholnik, Melissa Schori,
Tópico(s)Iron Metabolism and Disorders
ResumoNIH Conferences17 June 2008National Institutes of Health Consensus Development Conference Statement: Hydroxyurea Treatment for Sickle Cell DiseaseFREEOtis W. Brawley, MD, Llewellyn J. Cornelius, PhD, LCSW, Linda R. Edwards, MD, Vanessa Northington Gamble, MD, PhD, Bettye L. Green, RN, Charles Inturrisi, PhD, Andra H. James, MD, MPH, Danielle Laraque, MD, Magda Mendez, MD, Carolyn J. Montoya, RN, MSN, CPNP, Brad H. Pollock, MPH, PhD, Lawrence Robinson, MD, MPH, Aaron P. Scholnik, MD, and Melissa Schori, MD, MBA*Otis W. Brawley, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Llewellyn J. Cornelius, PhD, LCSWFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Linda R. Edwards, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Vanessa Northington Gamble, MD, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Bettye L. Green, RNFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Charles Inturrisi, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Andra H. James, MD, MPHFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Danielle Laraque, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Magda Mendez, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Carolyn J. Montoya, RN, MSN, CPNPFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Brad H. Pollock, MPH, PhDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Lawrence Robinson, MD, MPHFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, Aaron P. Scholnik, MDFrom Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this author, and Melissa Schori, MD, MBA*From Emory University and the American Cancer Society, Atlanta, Georgia; University of Maryland School of Social Work, Baltimore, Maryland; College of Medicine, University of Florida, Jacksonville, Jacksonville, Florida; The George Washington University, Washington, DC; Saint Joseph Regional Medical Center and African-American Women in Touch, South Bend, Indiana; Weill Medical College of Cornell University and Mount Sinai School of Medicine, New York, and Lincoln Medical and Mental Health Center, Bronx, New York; Women's Hemostasis and Thrombosis Clinic and Duke University Medical Center, Durham, North Carolina; National Association of Pediatric Nurse Practitioners and College of Nursing, University of New Mexico, Albuquerque, New Mexico; School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Philadelphia Department of Public Health, Philadelphia, Pennsylvania; Upper Peninsula Hematology/Oncology Associates and Cancer Research Office, Marquette General Health System, Marquette, Michigan; and Princeton Healthcare System, Princeton, New Jersey.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-12-200806170-00220 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail National Institutes of Health consensus and state-of-the- science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.Sickle cell disease is an inherited blood disorder that affects 50 000 to 100 000 people in the United States. It is estimated that 2000 babies are born with sickle cell disease in the United States each year. Sickle cell disease was the first disease for which a specific molecular defect in a gene was identified, and it is the most common genetic disease identified as part of the Newborn Screening Program in the United States. The condition is chronic and lifelong, and it is associated with a decreased lifespan. Sickle cell disease is most common in people whose families come from Africa, South or Central America, Caribbean islands, Mediterranean countries (such as Turkey, Greece, and Italy), India, and Saudi Arabia.Sickle cell disease occurs when an infant inherits the gene for sickle hemoglobin from both parents (Hb SS, or sickle cell anemia) or the gene for sickle hemoglobin from 1 parent and another abnormal hemoglobin gene from the other parent. In addition, approximately 2 million Americans have the sickle cell trait (in which an infant inherits the gene for sickle hemoglobin from 1 parent and a normal hemoglobin gene from the other parent). Several additional sickle syndromes result from genotypes that include, but are not limited to, SCD-Sβ0, SCD-SC, SCD-SD, SCD-Sβ+, and SCD-SOarab.Erythrocytes (red blood cells) in people with sickle cell disease become deoxygenated (depleted of oxygen), dehydrated, and crescent-shaped or “sickled.” The cells aggregate, or clump together, and stick to blood vessel walls. Aggregation blocks blood flow within limbs and organs. This can cause painful episodes and permanent damage to the eyes, brain, heart, lungs, kidneys, liver, bones, and spleen. Infections and lung disease are the leading causes of death in people with sickle cell disease.Patients with sickle cell disease are frequently seen in emergency departments and hospitalized for pain crises. Standard treatments for acute pain crises include painkilling medications, hydration, and oxygen.Hydroxyurea was initially synthesized in Germany in 1869. Nearly 50 years ago, it was developed as an anticancer drug and has been used to treat myeloproliferative syndromes, some types of leukemia, melanoma, and ovarian cancer. It has also been used to treat psoriasis. Hydroxyurea was first tested in sickle cell disease in 1984. Initial studies show that it acts to increase the production of fetal hemoglobin–containing erythrocytes and dilute the number of sickled cells in circulation.In the mid-1990s, investigators of a major study randomly assigned nearly 300 adults with sickle cell disease who had more than 3 severe painful crises or episodes per year to hydroxyurea or placebo. (In the past, the term pain crises has been used; currently, the term severe pain episodes is preferred.) This study was stopped early because it clearly showed that hydroxyurea reduced the number and severity of pain episodes in patients with sickle cell disease compared with placebo. Follow-up with the trial participants, including patients who were originally given placebo and were later prescribed hydroxyurea after the drug was determined to be beneficial, has shown that hydroxyurea reduces the damaging effects of sickle cell disease and improves some aspects of quality of life. The drug also may extend survival. In 1998, the U.S. Food and Drug Administration approved hydroxyurea for prevention of pain crises in adults with sickle cell anemia. Although the efficacy of hydroxyurea has been established in adults, the evidence of its efficacy in children is not as strong; however, the emerging data are supportive.Although hydroxyurea is beneficial to some patients with sickle cell disease, several issues about use of the drug are unresolved. These include patient and health practitioner concerns about the overall safety and effectiveness of hydroxyurea, as well as a lack of providers expert in the treatment of patients with sickle cell disease.To more closely examine this important topic, the National Heart, Lung, and Blood Institute and the Office of Medical Applications of Research of the National Institutes of Health convened a Consensus Development Conference from 25 to 27 February 2008 to assess the available scientific evidence related to the following questions: 1) What is the efficacy (results from clinical studies) of hydroxyurea treatment for patients who have sickle cell disease in 3 groups: infants, preadolescents, and adolescents and adults? 2) What is the effectiveness (in everyday practice) of hydroxyurea treatment for patients who have sickle cell disease? 3) What are the short- and long-term harms of hydroxyurea treatment? 4) What are the barriers to hydroxyurea treatment for patients who have sickle cell disease, and what are the potential solutions? 5) What are the future research needs?At the conference, invited speakers presented information pertinent to these questions, and a systematic literature review prepared under contract with the AHRQ (www.ahrq.gov/clinic/tp/hydscdtp.htm) was summarized. Conference attendees provided both oral and written statements in response to the key questions. The panel members weighed all of this evidence as they addressed the conference questions.This consensus statement is intended to provide researchers, health care providers, patients, and other interested members of the general public with an objective assessment of what is known about hydroxyurea as a treatment for sickle cell disease, and what questions remain.1. What Is the Efficacy (Results from Clinical Studies) of Hydroxyurea Treatment for Patients Who Have Sickle Cell Disease in 3 Groups: Infants, Preadolescents, and Adolescents and Adults?Efficacy is the therapeutic effect of an intervention in a controlled setting, in contrast to effectiveness, which is the therapeutic effect of an intervention in real-world situations. The spectrum of sickle cell disease includes the SCD-SS, SCD-Sβ0, SCD-SC, SCD-SD, SCD-Sβ+, and SCD-SOarab genotypes. Efficacy studies have varied in their inclusion of specific genotypes, but almost all include SCD-SS. In addition, the geographic origin of sickle cell disease is associated with different haplotypes and varying degrees of clinical severity. The 3 most common and phenotypically distinct haplotypes are Senegalese, Benin, and Bantu. Other geographic areas of origin associated with sickle cell disease include Saudi Arabia and the Indian subcontinent. The Benin and Bantu haplotypes are more common among people residing in the Western Hemisphere and are associated with worse clinical outcomes. Response to hydroxyurea therapy may vary by haplotype or genotype. However, few studies of efficacy have appropriately accounted for the heterogeneity of study populations that differed by genotype and phenotype as well as by demographic factors (such as sex and age).Although clinical experience on the use of hydroxyurea for treating sickle cell disease has been amassed over nearly 25 years, the strength of evidence supporting the efficacious use of hydroxyurea is not equivalent across age groups. Hydroxyurea is currently U.S. Food and Drug Administration–approved for use in adults and is the only treatment for sickle cell disease that modifies the disease process. Evidence is strong in adults but more limited in children because the sole randomized clinical trial in the latter population had a weak study design, small sample, and short follow-up. Nonetheless, the evidence in children does not contradict the findings in adults that hydroxyurea improves hematologic variables and decreases hospitalization rates. Published evidence based on weaker, observational study designs, such as cohort studies, before-and-after studies, case series, and case reports, suggests that hydroxyurea is efficacious. Adding to the difficulty in reaching a consensus on the use of hydroxyurea is that published efficacy studies are difficult to interpret because diverse outcome measures have been used, including hematologic end points; reduced incidence of severe pain episodes, the acute chest syndrome, hospitalizations, strokes, and kidney and spleen damage; and need for transfusion therapy. Studies currently under way should provide more information regarding the benefit of hydroxyurea in preventing organ damage and additional sickle cell disease outcomes. Elucidating the mechanism of action of hydroxyurea should prove useful in developing new agents.Adolescents and AdultsStrong evidence supports the efficacy of hydroxyurea use in adults. The published clinical trials included adolescents; however, they were not analyzed or reported as a separate group. Outcomes were diverse and included blood markers as measures of treatment effect (for example, hemoglobin level, hemoglobin F cell count, percentage of hemoglobin F, mean corpuscular volume, leukocyte count, and platelet count). Studies used a variety of clinical outcome measures (severe pain episodes, hospitalizations, the acute chest syndrome, blood transfusion therapy, mortality, priapism [unwanted, prolonged, painful erection], strokes, and leg ulcers) and examined the effects of hydroxyurea on the spleen, kidneys, and blood flow to the brain (Table 1).Table 1. Study Outcomes for Adults Receiving Hydroxyurea for Sickle Cell DiseaseAlthough a reduction in mortality with hydroxyurea therapy has been reported, the published trial was not specifically designed to assess this end point. It is therefore difficult to draw definitive conclusions about the effect of hydroxyurea on mortality.PreadolescentsThe evidence varies on whether the use of hydroxyurea improves short-term end points, especially hematologic measures, in preadolescent populations beyond infancy (Table 2).Table 2. Study Outcomes for Preadolescent Children beyond Infancy Receiving Hydroxyurea for Sickle Cell DiseaseEvidence is strong for an improvement in blood markers and reduced hospitalizations and moderate for a reduction in the incidence of pain crises. Ongoing investigations in this age group will determine the efficacy of hydroxyurea treatment for children with SCD-SS, a history of stroke, and too much iron (iron overload).InfantsNo published, well-designed clinical trials have evaluated the efficacy of hydroxyurea treatment for infants. Ongoing prospective trials and observational studies are attempting to address this gap. The end points of these studies include prevention of damage to the kidney and spleen and improvements in blood markers that predict long-term clinical outcomes.In summary, the efficacy of hydroxyurea treatment for adults with SCD-SS is established. Although the evidence for efficacy of hydroxyurea treatment for children is not as strong, the emerging data are supportive. Future directions include evaluation of efficacy in preadolescent children and infants and further development of other therapeutic techniques, including stem-cell transplantation and gene therapy. Stem-cell transplantation can cure sickle cell anemia.2. What Is the Effectiveness (in Everyday Practice) of Hydroxyurea Treatment for Patients Who Have Sickle Cell Disease?Effectiveness is the therapeutic effect of an intervention as demonstrated or observed in patients in their usual care setting. The efficacy of hydroxyurea in treating adults with sickle ce
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