Long-term hydroxyurea treatment in young sickle cell patients

Current Opinion in Hematology

Volumn 6, Issue 2, 1999, Pages 115-120

  Maier Redelsperger, Micheline ^a   Labie, Dominique ^a   Elion, Jacques ^a  

^a HÔPITAL TENON   (France)

Author keywords

[No Author keywords available]

Indexed keywords

HEMOGLOBIN; HYDROXYUREA;

ADOLESCENT; ADULT; BLOOD TRANSFUSION; CHILD; CLINICAL TRIAL; DISEASE COURSE; HUMAN; LONG TERM CARE; MAJOR CLINICAL STUDY; META ANALYSIS; PRIORITY JOURNAL; REVIEW; SICKLE CELL ANEMIA; THORAX DISEASE; TREATMENT OUTCOME;

ADOLESCENT; ADULT; ANEMIA, SICKLE CELL; ANTISICKLING AGENTS; CHILD; CHILD, PRESCHOOL; DOUBLE-BLIND METHOD; HUMANS; HYDROXYUREA; LONGITUDINAL STUDIES; RANDOMIZED CONTROLLED TRIALS; TREATMENT OUTCOME;

EID: 0032805842     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/00062752-199903000-00010     Document Type: Review

References (50)

1. Bunn HF: Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997, 337:762-769. This is an up-to-date review on the multiple aspects of the molecular pathogenesis of sickle cell disease and the ensuing approaches to therapy.
2. Swank RA, Stamatoyannopoulos G: Fetal gene reactivation. Curr Opin Genet Dev 1998, 8:366-370. This is a concise up-to-date review on the present understanding of the molecular control of the developmental switch of β-globin genes expression. Cellular and molecular bases of the pharmacologic reinduction of HbF and the various therapeutic approaches in patients with β-chain hemoglobinopathies are reported.
3. Stamatoyannopoulos G, Nienhuis AW: Hemoglobin switching. In The molecular basis of blood diseases. Edited by Stammatoyannopoulos G, Nienhuis AW, Majerus P, Varmus H. Philadelphia: WB Saunders; 1994:107-156.
4. Rodgers GP: Pharmacological modulation of fetal hemoglobin. In Sickle Cell Disease: Basic Principles and Clinical Practice. Edited by Embury SH, Hebbel RP, Mohandas N, Steinberg MH. Philadelphia: Lippincott-Raven; 1994:829-843.
5. Elion J, Labie D: Bases physiologiques moléculaires et cellulaires du traitement de la drépanocytose. Hématologie 1996, 2:499-510.
6. Olivieri NF, Weatherall DJ: The therapeutic reactivation of fetal haemoglobin. Hum Mol Genet 1998, 7:1655-1658.
7. Watson J, Stahman AW, Bilello FP: The significance of the paucity of sickle cells in newborn Negro infants. Am J Med Sci 1948, 215:419.
8. Pembrey ME, Wood WC, Weatherall DJ, Perrine RP: Fetal hemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia. Br J Haematol 1978, 49:415-429.
9. Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR: Pain in sickle cell disease: rates and risk factors. N Engl J Med 1991, 325:11-16.
10. DeSimone J, Heller P, Hall L, Zwiers D: 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc Natl Acad Sci U S A 1982, 79:4428-4431.
11. Charache S, Dover GJ, Smith K, Talbot CC, Moyer M, Boyer SH: Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the γ - β globin gene complex. Proc Natl Acad Sci U S A 1983, 80:4842-4846.
12. Ley TJ, DeSimone J, Noguchi CT, Turner PH, Schechter AN, Heller P, Nienhuis AW: Azacytidine increases gamma-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia. Blood 1983, 62:370-380.
13. Galanello R, Stammatoyannopoulos G, Papayannopoulou T: Mechanism of HbF stimulation by S-stage compounds: in vitro studies with bone-marrow cells exposed to 5-azacytidine, Ara-C, or hydroxyurea. J Clin Invest 1988, 81:1209-1216.
14. Platt OS, Orkin SH, Dover GJ, Beardsley GP, Miller B, Nathan DG: Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest 1984, 74:652-656.
15. Charache SC, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al., and the Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia: Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995, 332:1317-1322.
16. Charache S, Dover GJ, Moyer MA, Moore JW: Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia. Blood 1987, 69:109-116.
17. Triadou P, Maier-Redelsperger M, Krishnamoorthy R, Deschamps A, Casadevall N, Dunda O, et al.: Fetal haemoglobin variations following hydroxyurea treatment in patients with cyanotic congenital heart disease. Nouv Rev Fr Hematol 1994, 36:367-372.
18. Dover GJ, Humphries RK, Moore JG, Ley TJ, Young NS, Charache S, Nienhuis AW: Hydroxyurea induction of hemoglobin F production in sickle cell disease: relationship between cytoxicity and F cell production. Blood 1986, 67:735-738.
19. Ohene-Frempong K, Horiuchi K, Stoeckert C, Tournier B, Mameniskis H, Schursky H, et al.: Sustained effect of hydroxyurea on HbF production in children with sickle cell disease. 20th Annual Meeting of the National Sickle Cell Disease Program, Boston, MA, March 1995.
20. Scott JP, Hillery CA, Brown ER, Misiewicz V, Labotka RJ: Hydroxyurea therapy in children severely affected with sickle cell disease. J Pediatr 1996, 128:820-828.
21. Ferster A, Vermylen C, Cornu G, Buyse M, Corazza F, Devalck C, et al.: Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood 1996, 88:1960-1964.
22. Jayabose S, Tugal O, Sandoval C, Patel P, Puder D, Lin T, Visintainer P: Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia. J Pediatr 1996, 129:559-565.
23. de Montalembert M, Belloy M, Bernaudin F, Gouraud F, Capdeville R, Mardini R, et al.: Three-years follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. J Pediatr Hematol Oncol 1997, 19:313-318.
24. Maier-Redelsperger M, de Montalembert M, Flahault A, Neonato MG, Ducrocq R, Masson MP, et al.: Fetal hemoglobin and F-cell responses to long-term hydroxyurea treatment in young sickle cell patients. Blood 1998, 91: 4472-4479. This is a detailed study of the long-term molecular and cellular responses in a subset of the largest pediatric trial [23]. This study best illustrates the high interindividual variability of the biologic response. Making three groups of patients according to the maximal HbF achieved shows that the best responders are those with the highest initial HbF.
25. Rogers ZR: Hydroxyurea therapy for diverse pediatric populations with sickle cell disease. Semin Hematol 1997, 34:42-47.
26. Olivieri NF, Vichinsky EP: Hydroxyurea in children with sickle cell disease: impact on splenic function and compliance with therapy. J Pediatr Hematol Oncol 1998, 20:26-31.
27. Ohene-Frempong K, Smith-Whitley K: Use of hydroxyurea in children with sickle cell disease: what comes next? Semin Hematol 1997, 34:30-41. Despite the many well-organized clinical trials of HU that have now provided definite proof of its efficacy, mainly in adult SCD patients, no large-scale effort has been devoted to develop and disseminate treatment protocols. Thus, many questions arise and have to be resolved before the widespread correct use of HU. Guidelines have to be established to support clinicians, especially pediatricians, in the use of this drug. The authors review these unanswered questions, more specifically, those relevant to the use of HU in children, and offer statements regarding patient selection criteria, goals of therapy, dosing schedules, and monitoring.
28. Weinfeld A, Swolin B, Westin J: Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: prospective study of efficacy and leukaemogenicity with therapeutic implications. Eur J Haematol 1994, 52:134-139.
29. Sterkers Y, Preudhomme C, Lai JL, Demory JL, Caulier MT, Wattel E, et al.: Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion. Blood 1998, 91:616-622.
30. Steinberg MH, Lu Z-H, Barton FB, Terrin ML, Charache S, Dover GJ, and the Multicenter Study of Hydroxyurea: Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Blood 1997, 89:1078-1088. Looking for predicting factors of the HbF response in MSH patients, the authors hypothesize that the ability to respond to HU could be related to bone marrow reserve reflected by baseline reticulocyte and neutrophil counts.
31. Charache S: Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol 1997, 34:15-21.
32. s-haplotypes on HbF response to hydroxyurea in sickle cell disease. Blood 1995, 86:139a.
33. Vichinsky EP: Hydroxyurea in children: present and future. Semin Hematol 1997, 34:22-29.
34. Claster S, Vichinsky E: First report of reversal of organ dysfunction in sickle cell anemia by the use of hydroxyurea: splenic regeneration. Blood 1996, 88:1951-1953.
35. Perrine SP, Rudolph A, Faller DV, Roman C, Cohen RA, Chen SJ, Kan YW: Butyrate infusions in the ovine fetus delay the biologic clock for globin gene switching. Proc Natl Acad Sci U S A 1988, 85:8540-8542.
36. Fritz H, Hess R: Effects of hydroxyurea on postnatal growth and behaviour of rats. Agents Actions 1980, 10:389-393.
37. Milner P, Kutlar A, Pantazis C, Nagel R: HbF response in sickle cell anemia to a constant daily dose of hydroxyurea without escalation to maximal tolerated dose. 19th Annual Meeting of the National Sickle Cell Disease Program, New York City, March 1994.
38. Rodgers GP, Dover GJ, Uyesaka N, Noguchi CT, Schechter AN, Nienhuis AW: Augmentation by erythropoietin of the fetal-hemoglobin response to hydroxyurea in sickle cell disease. N Engl J Med 1993, 328:73-80.
39. Faller DV, Perrine SP: Butyrate in the treatment of sickle cell disease and beta-thalassemia. Curr Opin Hematol 1995, 2:109-117.
40. Brugnara C, Gee B, Armsby CC, Kurth S, Sakamoto M, Rifai N, et al.: Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease. J Clin Invest 1996, 97:1227-1234.
41. de Franceschi L, Bachir D, Galacteros F, Tchernia G, Cynober T, Alper S, et al.: Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease. J Clin Invest 1997, 100:1847-1852.
42. Adams-Graves P, Kedar A, Koshy M, Steinberg M, Veith R, Ward D, et al.: RheothRx (Poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study. Blood 1997, 90:2041-2046.
43. Bridges KR, Barabino GD, Brugnara C, Cho MR, Christoph GW, Dover G, et al.: A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy. Blood 1996, 88:4701-4710.
44. Mohandas N, Ballas SK: Erythrocyte density and heterogeneity. In Sickle cell disease: basic principles and clinical practice. Edited by Embury SH, Hebbel RP, Mohandas N, Steinberg MH. Philadelphia: Lippincott-Raven; 1994:195-203.
45. Styles LA, Lubin B, Vichinski E, Lawrence S, Hua M, Test S, Kuypers F: Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea. Blood 1997, 89:2554-2559. Expression of the VLA 4 and CD36 adhesion receptors decreases on reticulocytes of SCD patients treated by HU, before a substantial HbF increase is observed. This might be the first link between an HU-induced biologic alteration and the early beneficial effect observed clinically.
46. Kinney TR, HUG-KIDS Study Group: Phase I/II multicenter pediatric trial of hydroxyurea (HUG-KIDS). Blood 1997, 90:445a.
47. de Montalembert M, Belloy M, Bernaudin F, Thuret I, Lacoste C, Migeon F: Short and middle-term tolerances of hydroxyurea in sickle cell children. Blood 1997, 90:445a.
48. Ferster A: Pharmacological stimulation of fetal hemoglobin in SCD: creation of the Belgian Registry on Hydroxyurea in severe sickle cell disease and other hemoglobinopathies. IInd International symposium on the red blood cell, Brussels, Belgium, September 1998.
49. Davies SC, Roberts-Harwood M: European register of patients with sickle cell disease treated with hydroxyurea is being set up. BMJ 1998, 317:541a.
50. Deconinck N, Tinsley J, De Backer F, Fisher R, Kahn D, Phelps S, et al.: Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice. Nat Med 1997, 3:1216-1221.