[en] Objective. To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT). Method. The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from neonatal screening or from diagnosis (first contact) until last follow-up or death. Data included diagnosis, demography, and outcome data. Results. We collected data from 469 patients over a 5,110 patient years (PY) follow-up period. The global mortality rate was low (0.25/100 PY), although 13 patients died (2.8%) and was similar between children, adolescents (10–18 years), and young adults (P¼0.76). Out of the cohort, 185 patients received hydroxyurea at last follow-up (median duration of treatment: 10.3 years), 90 underwent hematopoietic stem cell transplantation (HSCT), 24 were chronically transfused, and 170 had never had any DMT. Hydroxyurea showed significant benefit on patients
outcome as reflected by a lower mortality rate compared to transplanted individuals or people without DMT (0.14, 0.36, and 0.38 per 100 PY, respectively) and by higher Kaplan–Meier estimates of 15 year survival (99.4%) compared to HSCT (93.8%; P¼0.01) or
no DMT groups (95.4%; P¼0.04). Conclusion. SCD mortality in Belgium is low with no increase observed in young adults. Patients treated with hydroxyurea demonstrate a significant benefit in survival when compared to those withoutDMTor transplanted.
Disciplines :
Pediatrics
Author, co-author :
Lê, Phu Quoc
Gulbis, Béatrice
Dedeken, Laurence
Dupont, Sophie
Vanderfaeillie, Anna
Heijmans, Catherine
Huybrechts, Sophie
Devalck, Christine
Efira, André
DRESSE, Marie-Françoise ; Centre Hospitalier Universitaire de Liège - CHU > Service de pédiatrie (CHR)
Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS, Diamond S, Holbrook CT, Gill FM, Ritchey K, Falletta JM, and for the Prophylactic Penicillin Study Group. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. New Engl J Med 1986; 314:1593-1599.
Davies EG, Riddington C, Lottenberg R, Dower N. Pneumococcal vaccines for sickle cell disease. Cochrane Database Syst Rev 2004; 1:CD003885.
Adamkiewicz TV, Silk BJ, Howgate J, Baughman W, Strayhorn G, Sullivan K, Farley MH. Effectiveness of the 7-valent pneumococcal conjugate vaccine in children with sickle cell disease in the first decade of life. Pediatrics 2008; 121:562-569.
Yanni E, Grosse SD, Yang Q, Olney RS. Trends in pediatric sickle cell disease-related mortality in the United States, 1983-2002. J Pediatr 2009; 154:541-545.
Voskaridou E, Christoulas D, Bilalis A, Plata E, Varvagiannis K, Stamatopoulos G, Sinopoulou K, Balassopoulou A, Loukopoulos D, Terpos E. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndrome: Results of a 17-year, single-center trial (LaSHS). Blood 2010; 115:2354-2363.
Hamideh D, Alvarez O. Sickle cell disease related mortality in the United States (1999-2009). Pediatr Blood Cancer 2013; 60:1482-1486.
Lobo CL, Pinto JF, Nascimento EM, Moura PG, Cardoso GP, Hankins JS. The effect of hydroxycarbamide therapy on survival of children with sickle cell disease. Br J Haematol 2013; 161:852-860.
Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B. Newborn screening for sickle cell disease: Effect on mortality. Pediatrics 1988; 81:749-755.
Adams RJ, Nichols FT, Figueroa R, McKie V, Lott T. Transcranial Doppler correlation with cerebral angiography in sickle cell disease. Stroke 1992; 23:1073-1077.
Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, Abboud M, Gallagher D, Kutlar A, Nichols FT, Bonds DR, Brambilla D. Prevention of a first stroke by transfusion in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. New Engl J Med 1998; 339:5-11.
Bernaudin F, Verlhac S, Arnaud C, Kamdem A, Chevret S, Hau I, Coïc L, Leveillé E, Lemarchand E, Lesprit E, Abadie I, Medejel N, Madhi F, Lemerle S, Biscardi S, Bardakdjian J, Galactéros F, Torres M, Kuentz M, Ferry C, Socié G, Reinert P, Delacourt C. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood 2011; 117:1130-1140.
Thomas C, Lemerle S, Bernaudin F, Feingold J, Guillou-Bataille M, Reinert P. Sickle cell anemia: Study of the pediatric mortality in Ile de France from 1985 to 1992. Arch Pédiatr 1996; 3:445-451.
Neonato MG, Guilloud-Bataille M, Beauvais P, Bégué P, Belloy M, Benkerrou M, Ducrocq R, Maier-Redeisperger M, de Montalembert M, Quinet B, Elion J, Feingold J, Girot R. Acute clinical events in 299 homozygous sickle cell patients living in France. Eur J Haematol 2000; 65:55-164.
Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood 2004; 103:4023-4027.
Telfer P, Coen P, Chakravorty S, Wilkey O, Evans J, Newell H, Smalling B, Amos R, Stephens A, Rogers D, Kirkham F. Clinical outcomes in children with sickle cell disease living in England: A neonatal cohort in East England. Haematologica 2007; 92:905-912.
Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood 2010; 115:3447-3452.
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. New Engl J Med 1994; 330:1639-1644.
Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, Nickerson O, Orringer E, McKie V, Bellevue R, Daeschner C, Manci EA. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. New Engl J Med 2000; 342:1855-1865.
Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: A 4-decade observational study of 1056 patients. Medicine 2005; 84:363-376.
Fitzhugh CD, Lauder N, Jonassaint JC, Telen MJ, Zhao X, Wright EC, Gilliam FR, De Castro LM. Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am J Hematol 2010; 85:36-40.
Gardner K, Bell C, Bartram JL, Allman M, Awogbade M, Rees DC, Ervine M, Thein SL. Outcome of adults with sickle cell disease admitted to critical care-Experience of a single institution in the UK. Br J Haematol 2010; 150:610-613.
Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crisis in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. New Engl J Med 1995; 332:1317-1322.
Ferster A, Vermylen C, Cornu G, Buyse M, Corazza F, Devalck C, Fondu P, Toppet M, Sariban E. Hydroxyurea for treatment of severe sickle cell anemia: A pediatric clinical trial. Blood 1996; 88:1960-1964.
Gulbis B, Haberman D, Dufour D, Christophe C, Vermylen C, Kagambega F, Corraza F, Devalck C, Dresse MF, Hunnick K, Klein A, Le PQ, Loop M, Maes P, Philippet P, Sariban E, Van Geet C, Ferster A. Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: The Belgian experience. Blood 2005; 105:2685-2690.
Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood 2010; 115:5300-5311.
Vermylen C, Cornu G, Ferster A, Brichard B, Ninane J, Ferrant A, Zenebergh A, Maes P, Dhooge C, Benoit Y, Beguin Y, Dresse MF, Sariban E. Haematopoietic stem cell transplantation for sickle cell anemia: The first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22:1-6.
Walters MC, Patience M, Leisenring W, Eckman JR, Scott JP, Mentzer WC, Davies SC, Ohene-Frempong K, Bernaudin F, Matthiews DS, Storb R, Sullivan KM. Bone marrow transplantation for sickle cell disease. New Engl J Med 1996; 335:369-376.
Panepinto JA, Walters MC, Carreras J, Marsh J, Bredeson CN, Gale RP, Hale GA, Horan J, Hows JM, Klein JP, Pasquini R, Roberts I, Sullivan K, Eapen M, Ferster A. Non-malignant marrow disorders working committee, center for international blood and marrow transplant research. matched-related donor transplantation for sickle cell disease: Report from the center for international blood and transplant research. Br J Haematol 2007; 137:479-485.
Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y, Vannier JP, Yakouben K, Thuret I, Bordigoni P, Fischer A, Lutz P, Stephan JL, Dhedin N, Plouvier E, Margueritte G, Bories D, Verlhac S, Esperou H, Coic L, Vernant JP. Gluckman E; SFGM-TC. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood 2007; 110:2749-2756.
Dedeken L, Lê P-Q, Azzi N, Brachet C, Heijmans C, Huybrechts S, Devalck C, Rozen L, Ngalula M, Ferster A. Hematopoietic stem cell transplantation for severe sickle cell disease in childhood: A single centre experience of 50 patients. Br J Haematol 2014; 165:402-408.
Rees DC, Olujohungbe AD, Parker NE, Stephens AD, Telfer P, Wright J. British committee for standards in haematology general haematology task force by the sickle cell working party. Guidelines for the management of the acute pain crisis in sickle cell disease. Br J Haematol 2003; 120:744-752.
de Montalembert M, Brousse V, Elie C, Bernaudin F, Shi J, Landais P. French study group on sickle cell disease. Long term hydroxyurea treatment in children with sickle cell disease: Tolerance and clinical outcomes. Haematologica 2006; 91:125-128.
de Montalembert M, Ferster A, Colombatti R, Rees DC, Gulbis B. European network for rare and congenital anaemias. ENERCA clinical recommendations for disease management and prevention of complications of sickle cell disease in children. Am J Hematol 2011; 86:72-75.
Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sicke cell disease: Summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033-1048.
Gill FM, Sleeper LA, Weiner SI, Brown AK, Bellevue R, Grover R, Pegelow CH, Vichinsky E. Clinical events in the first decade in a cohort of infants with sickle cell disease. Coopperative study of sikle cell disease. Blood 1995; 86:776-783.
Lanzkron S, Carroll CP, Haywood C, Jr. Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep 2013; 128:110-116.
Strousse JJ, Lanzkron S, Beach MC, Haywood C, Park H, Witkop C, Wilson RF, Bass EB, Segal JB. Hydroxyurea for sickle cell disease: A systematic review for efficacy and toxicity in children. Pediatrics 2008; 122:1332-1342.
Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW, BABYHUG investigators. Hydroxycarbamide in very young children with sickle-cell anemia: A multicentre, randomised, controlled trial (BABY HUG). Lancet 2011; 377:1663-1672.
Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC, BABYHUG Investigators. Impact of hydroxyurea on clinical events in the BABYHUG trial. Blood 2012; 120:4304-4310.
Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment. JAMA 2003; 289:1645-1651.
Steinberg MH, McCarthy WF, Castro O, Ballas SK, Armstrong FD, Smith W, Ataga K, Swerdlow P, Kutlar A, DeCastro L, Waclawiw MA. Investigators of the multicenter study of hydroxyurea in sikle cell anemia and MSH patients' follow-up. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up. Am J Hematol 2010; 85:403-408.
Gulbis B, Ferster A, Vermylen C, Dresse MF, Vanderfaeillie A, Delannoy A, Labarque V, Philippet P, Kentos A, Sztern B, Deprijck B, Vertongen F. Red blood cell disorders subcommittee of the Belgian Haematological Society. An estimation of the incidence and demographic picture of the major hemoglobinopathies in Belgium (from a confidential inquiry). Hemoglobin 2008; 32:279-285.
Miller AC, Gladwin MT. Pulmonary complications of sickle cell disease. Am J Respir Crit Care Med 2012; 185:54-65.
Gladwin MT, Barst RJ, Gibbs JS, Hildesheim M, Sachdev V, Nouraie M, Hassell KL, Little JA, Schraufnagel DE, Krishnamurti L, Novelli E, Girgis RE, Morris CR, Berman Rosenzweig, Lanzkron DB, Castro S, . Taylor JG 6th, Goldsmith JC, Kato GJ, Gordeuk VR, Machado RF, walk-PHaSST investigators and Patients. Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom. PLoS One 2014; 9:e99489. doi:10.1371/journal.pone.0099489.
