Clinical and hematological effects of hydroxyurea therapy in sickle cell patients
a single-center experience in Brazil
Keywords:
Anemia, sickle cell, Hydroxyurea, Fetal hemoglobin, Acute chest syndrome, Erythrocyte indicesAbstract
CONTEXT AND OBJECTIVES: Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING: Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS: We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS: There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION: The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies.
Downloads
References
Eaton JW, Hebbel RP. Pathogenesis of sickle cell disease. Pathobiol Annu. 1981;11:31-52.
Hebbel RP, Eaton JW, Steinberg MH, White JG. Erythrocyte/endothelial interactions and the vasocclusive severity of sickle cell disease. Prog Clin Biol Res. 1981;55:145-62.
Davies SC, Gilmore A. The role of hydroxyurea in the management of sickle cell disease. Blood Rev. 2003;17(2):99-109.
Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003;289(13):1645-51.
Voskaridou E, Christoulas D, Bilalis A, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115(12):2354-63.
Steinberg MH, Lu ZH, Barton FB, et al. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea. Blood. 1997;89(3):1078-88.
Olivieri NF, Weatherall DJ. The therapeutic reactivation of fetal haemoglobin. Hum Mol Genet. 1998;7(10):1655-8.
Ho JA, Pickens CV, Gamcsik MP, Colvin OM, Ware RE. In vitro induction of fetal hemoglobin in human erythroid progenitor cells. Exp Hematol. 2003;31(7):586-91.
Fathallah H, Atweh GF. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2006;58-62.
Maier-Redelsperger M, de Montalembert M, Flahault A, et al. Fetal hemoglobin and F-cell responses to long-term hydroxyurea treatment in young sickle cell patients. The French Study Group on Sickle Cell Disease. Blood. 1998;91(12):4472-9.
Steinberg MH. Determinants of fetal hemoglobin response to hydroxyurea. Semin Hematol. 1997;34(3 Suppl 3):8-14.
Borba R, Lima CS, Grotto HZ. Reticulocyte parameters and hemoglobin F production in sickle cell disease patients undergoing hydroxyurea therapy. J Clin Lab Anal. 2003;17(2):66-72.
Styles LA, Lubin B, Vichinsky E, et al. Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood. 1997;89(7):2554-9.
Covas DT, de Lucena Angulo I, Vianna Bonini Palma P, Zago MA. Effects of hydroxyurea on the membrane of erythrocytes and platelets in sickle cell anemia. Haematologica. 2004;89(3):273-80.
Brugnara C. Therapeutic strategies for prevention of sickle cell dehydration. Blood Cells Mol Dis. 2001;27(1):71-80.
Bookchin RM, Lew VL. Sickle red cell dehydration: mechanisms and interventions. Curr Opin Hematol. 2002;9(2):107-10.
Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995;332(20):1317-22.
Ware RE, Eggleston B, Redding-Lallinger R, et al. Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood. 2002;99(1):10-4.
Ferster A, Tahriri P, Vermylen C, et al. Five years of experience with hydroxyurea in children and young adults with sickle cell disease. Blood. 2001;97(11):3628-32.
Kinney TR, Helms RW, O’Branski EE, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94(5):1550-4.
Zimmerman SA, Schultz WH, Davis JS, et al. Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease. Blood. 2004;103(6):2039-45.
Charache S, Dover GJ, Moore RD, et al. Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia. Blood. 1992;79(10):2555-65.
Ma Q, Wyszynski DF, Farrell JJ, et al. Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea. Pharmacogenomics J. 2007;7(6):386-94.
Lobo C, Hankins JS, Moura P, Pinto JC. Hydroxyurea therapy reduces mortality among children with sickle cell disease. Blood (ASH Annual
Meeting Abstracts). 2010;116(21):abstract 843. Available from: http:// abstracts.hematologylibrary.org/cgi/content/abstract/116/21/843? maxtoshow=&hits=10&RESULTFORMAT=&fulltext=Hydroxyurea+th erapy+reduces+mortality+among+children+with+sickle+cell+dise ase&searchid=1&FIRSTINDEX=0&volume=116&issue=21&resourcety pe=HWCIT. Accessed in 2012 (Sep 12).
Ballas SK, Barton FB, Waclawiw MA, et al. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes. 2006;4:59.
Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115(17):3447-52.
Thompson BW, Miller ST, Rogers ZR, et al. The pediatric hydroxyurea phase III clinical trial (BABY HUG): challenges of study design. Pediatr Blood Cancer. 2010;54(2):250-5.
Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood. 2010;115(26):5300-11.
McGann PT, Ware RE. Hydroxyurea for sickle cell anemia: what have we learned and what questions still remain? Curr Opin Hematol. 2011;18(3):158-65.
Steinberg MH, McCarthy WF, Castro O, et al. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow- up. Am J Hematol. 2010;85(6):403-8.
