Importance of escalation of hydroxyurea to maximum tolerated dose to achieve a sustained HbF response
. | No. patients . | . | Hb response . | . | . | MCV response . | . | . | Percentage HbF response . | . | . | ANC response . | . | . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Year . | Duke . | Belgian . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | |||||||||
| 0 | 114 | 93 | 8.0 ± 1.0 | 8.2 ± 1.1 | NS | 85 ± 9 | 83 ± 8.9 | NS | 8.0 ± 5.5 | 7.3 ± 6.8 | NS | 6.4 ± 2.9 | 6.0 ± 2.6 | NS | |||||||||
| 1 | 114 | 83 | 9.4 ± 1.1 | 8.8 ± 1.2 | < .001 | 105 ± 13 | 93.5 ± 11 | < .001 | 21.2 ± 7.8 | 16.7 ± 10.6 | < .001 | 3.7 ± 1.9 | 3.9 ± 1.8 | NS | |||||||||
| 2 | 90 | 61 | 9.5 ± 1.2 | 9.0 ± 1.5 | .025 | 105 ± 12 | 93.4 ± 11 | < .001 | 20.8 ± 7.3 | 16.1 ± 9.7 | < .001 | 3.6 ± 2.0 | 4.5 ± 2.5 | .015 | |||||||||
| 3 | 64 | 44 | 9.6 ± 1.2 | 8.7 ± 1.2 | < .001 | 106 ± 12 | 94.6 ± 12 | < .001 | 20.6 ± 8.0 | 15.6 ± 8.7 | .003 | 3.5 ± 2.2 | 4.2 ± 2.5 | NS | |||||||||
| 4 | 44 | 33 | 9.8 ± 1.2 | 8.2 ± 1.4 | < .001 | 106 ± 13 | 95.8 ± 12 | < .001 | 20.2 ± 8.2 | 15.3 ± 8.0 | .011 | 3.6 ± 2.2 | 4.2 ± 2.0 | NS | |||||||||
| 5 | 34 | 22 | 9.8 ± 1.5 | 8.7 ± 1.3 | .007 | 109 ± 13 | 96.9 ± 15 | .002 | 21.0 ± 8.8 | 12.9 ± 6.7 | < .001 | 3.0 ± 1.4 | 4.0 ± 2.3 | .048 | |||||||||
. | No. patients . | . | Hb response . | . | . | MCV response . | . | . | Percentage HbF response . | . | . | ANC response . | . | . | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Year . | Duke . | Belgian . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | Duke . | Belgian . | P . | |||||||||
| 0 | 114 | 93 | 8.0 ± 1.0 | 8.2 ± 1.1 | NS | 85 ± 9 | 83 ± 8.9 | NS | 8.0 ± 5.5 | 7.3 ± 6.8 | NS | 6.4 ± 2.9 | 6.0 ± 2.6 | NS | |||||||||
| 1 | 114 | 83 | 9.4 ± 1.1 | 8.8 ± 1.2 | < .001 | 105 ± 13 | 93.5 ± 11 | < .001 | 21.2 ± 7.8 | 16.7 ± 10.6 | < .001 | 3.7 ± 1.9 | 3.9 ± 1.8 | NS | |||||||||
| 2 | 90 | 61 | 9.5 ± 1.2 | 9.0 ± 1.5 | .025 | 105 ± 12 | 93.4 ± 11 | < .001 | 20.8 ± 7.3 | 16.1 ± 9.7 | < .001 | 3.6 ± 2.0 | 4.5 ± 2.5 | .015 | |||||||||
| 3 | 64 | 44 | 9.6 ± 1.2 | 8.7 ± 1.2 | < .001 | 106 ± 12 | 94.6 ± 12 | < .001 | 20.6 ± 8.0 | 15.6 ± 8.7 | .003 | 3.5 ± 2.2 | 4.2 ± 2.5 | NS | |||||||||
| 4 | 44 | 33 | 9.8 ± 1.2 | 8.2 ± 1.4 | < .001 | 106 ± 13 | 95.8 ± 12 | < .001 | 20.2 ± 8.2 | 15.3 ± 8.0 | .011 | 3.6 ± 2.2 | 4.2 ± 2.0 | NS | |||||||||
| 5 | 34 | 22 | 9.8 ± 1.5 | 8.7 ± 1.3 | .007 | 109 ± 13 | 96.9 ± 15 | .002 | 21.0 ± 8.8 | 12.9 ± 6.7 | < .001 | 3.0 ± 1.4 | 4.0 ± 2.3 | .048 | |||||||||
Comparison is between 114 Duke patients with severe sickle genotypes, including HbSS, HbS/β0, and HbS/OArab, who received hydroxyurea at MTD and 93 patients who participated in the Belgian registry as reported by Ferster et al. 12 Hydroxyurea doses of the Duke patients were increased to MTD, with an average dose of 25.4 mg/kg per day. In the Belgian study, 12 most of the 93 patients were maintained on hydroxyurea doses lower than 20 to 25 mg/kg per day, and only 5% of those patients received 25 to 30 mg/kg per day. Values represent mean ± 1 SD.
NS indicates not significant.