Table 1

Clinical studies evaluating hydroxyurea therapy in patients with β-thalassemia

ReferenceSampleAge (y)*HU dose (mg/kg per d)*Duration (mo)Total Hb (g/L)*Fetal Hb*Comments
Karimi et al65  126 TM 22.3 10 96-156 Baseline: 85-100 — TI: NTD or TD [intermittent] 
Final: ≥90 (n = 51 [40%])  TM: 86 [68.3%] TD → NTD, 25 [19.8%] TD → 1 or 2 transfusions 
Final: ≥80 to <90 (n = 44 [35%])  
Final: ≥70 to <80 (n = 16 [13%])  
Final: <70 (n = 15 [12%])  
106 TI 18.1 10 96-156 Δ: +≥20 (n = 12 [11%]) — 
Δ: +10 to <20 (n = 44 [42%]) 
Δ: +<10 (n = 47 [44%]) 
Δ: no change (n = 3 [3%]) 
Amoozgar et al66  33 TI 20 10 12 Baseline: 98.4 Baseline: 79.3 g/L TI: NTD or TD [intermittent] 
Δ: +13.4† Δ: +8.0 g/L‡ 
51 TI 17 None 12 Baseline: 92.8 — 
Δ: +4.7‡   
Ansari et al67  119 TM 2.6-25 16 24 -Baseline: 75 Baseline: 11.2% TI: NTD 
Δ: +1‡ (responders, n = 33 [27.7%]) Δ: +88.4% (responders) Responders: TD → NTD 
-Baseline: 82  Partial responders: >50% ↓ in transfusion need 
Δ: −14† (partial responders, n = 57 [47.9%])  
-Baseline: 79  Nonresponders: <50% ↓ in transfusion need 
Δ: −13† (nonresponders, n = 29 [24.4%])  
27 TI 3-13 16 24 Baseline: 67 Baseline: 98.5%  
Δ: +11† Δ: +1.4%  
Italia et al68  13 Hb E/β-thalassemia 8-34 15-20 17-23 -Baseline: 61 -Baseline: 22.3% Responders: TD → NTD 
(median 20) Δ: +11† (responders, n = 6 [46.2%]) Δ: +16%† (responders) Partial responders: ↓ in transfusion need (30% to 50%) 
-Baseline: 63 F cells: +25.8%† 
Δ: 0‡ (partial responders, n = 4 [30.8%]) -Baseline: 15.2% Nonresponders: no change in transfusion need 
-Baseline: 76 Δ: +16.6%‡ (partial responders) 
Δ: −12‡ (nonresponders, n = 3 [23.1%]) F cells: +18.5%‡ 
-Baseline: 2.9% 
Δ: +5.8%† (nonresponders) 
F cells: +13.3%† 
Karimi et al69  143 TI 21 10.7 18-120 Baseline: 74 — TI: NTD or TD 
   (median 68.4) Δ: +23†   
Rigano et al50  24 TI 37 14.6 12 Baseline: 78 Baseline: 46.5% TI: NTD 
Δ: +15† Δ: +10.7%† 17 patients with ΔHb > 10 g/L followed for >12 mo (mean: 68 mo); 9 maintained response, while 8 had reduction 
Ehsani et al70  16 TI 10.7 20 6 Δ: +16 Δ: +17 g/L TI: NTD 
Italia et al44  41 TM 12-28 15-20 20-24 -Baseline: 81 -Baseline: 5.4% TI: TD [intermittent] or TD 
Δ: −5‡ (partial responders, n = 13 [31.7%]) Δ: +32%† (partial responders) Responders: TD → NTD 
-Baseline: 76 F cells: +40.9%† Partial responders: >50% ↓ in transfusion need 
Δ: −5‡ (nonresponders, n = 28 [68.3%]) -Baseline: 3.7% 
Δ: +8.2%† (nonresponders) Dose increases to 30 mg/kg per day in nonresponders had no benefit 
F cells: +13.8%† 
38 TI 5-40 15-20 20-24 -Baseline: 76 -Baseline: 51.8%  
Δ: +15† (responders, n = 22 [57.9%]) Δ: +35.4%† (responders) 
-Baseline: 79 F cells: +27.4%† 
Δ: −2‡ (partial responders, n = 6 [15.8%]) -Baseline: 6.3% 
-Baseline: 63 Δ: +31.1%† (partial responders) 
Δ: −2‡ (nonresponders, n = 10 [26.3%]) F cells: +33.3%† 
-Baseline: 25.9% 
Δ: +20%† (nonresponders) 
F cells: +32.8%† 
Zamani et al71  49 TM 18.4 10 12 Baseline: 85.2 — Mean number of transfused units ↓ from 22.8 → 6.0† 
Δ: −0.7† 
12 [24.5%] became NTD 
 
Koren et al72  11 TM 18 10.9 5-60 Responders, n = 9 [81.8%] Baseline: 83% TI: NTD or TD [intermittent] 
(median 24) Δ: −1% (1 y) ‡, −5% (2 y) ‡ Responders: TD → NTD (maintaining an Hb of 70 g/L in TM and 60 g/L in TI) 
7 TI 18 10.9 36-96 -Baseline: 67 Baseline: 15%  
(median 60) Δ: +2 (5 TD, responders, n = 5 [100%]) Δ: +13%‡ (1 y), +8% (2 y) ‡ 
-Baseline: 66 
Δ: +18 (2 NTD) 
Mtvarelidze et al73  6 TM 9.8 15 60 Baseline: 94 Baseline: 23% 3 [50%] patients: TD → NTD 
Δ: +1 (12 mo), +3 (60 mo) Δ: +8.3% (12 mo), +20.4 (60 mo) 2 [33.3%] patients: ↓ in transfusion need after 1 y 
Ansari et al74  23 TM 8.7 16 24 Baseline: 86 — 42.8% ↓ in blood volume transfused 
Δ: −14 68.7% ↑ in transfusion interval 
Bradai et al75  45 TM 10 17.4 12 Δ: +15 (good responders, n = 20 [44.4%]) — TI: TD 
Δ: +7 (partial responders, n = 9 [20%]) Good responders: >70% ↓ in transfusion need 
Δ: +2 (nonresponders, n = 16 [35.6%]) 
 Partial responders: 40% to 70% ↓ in transfusion need 
9 TI 12.5 17 12 Δ: +37 (8 good responders [88.9%], 1 nonresponder [11.1%]) — Nonresponders: <40% ↓ in transfusion need 
Mancuso et al76  18 TI 37 14.6 12 Δ: +15† — TI: NTD 
11 patients with ΔHb > 10 g/L were followed for >12 mo (mean: 66 mo); 7 maintained response, while 4 had reduction 
Taher and Sheikh-Taha84  7 TI 24 10-20 6-46 Baseline: 70 — TI: NTD 
(median 12) Δ: +5 
Singer et al85  45 Hb E/β-thalassemia 13 18-20 24 Baseline: 68 Baseline: 29.8% Patients weaned off transfusions before study 
Δ: +6 Δ: +6.7% 
  16 [38%] patients had ΔHb > 10 g/L 
Dixit et al77  37 TM + TI 10 10->20 6 -Baseline: 65 -Baseline: 67% -TI: NTD, TD [intermittent], or TD 
Δ: +26† (major responders, n = 17 [45.9%]) Δ: +9%† (major responders) Major responders: TD → NTD (Hb > 80 g/L), or Hb ↑ >20 g/L 
-Baseline: 63 -Baseline: 70.2% 
Δ: +18† (minor responders, n = 9 [24.3%]) Δ: +8.5‡ (minor responders) Minor responders: TD → NTD (Hb < 80 g/L), >50% ↓ in transfusion need, or Hb ↑ 10 to 20 g/L 
-Baseline: 65 -Baseline: 40.9% 
Δ: +5† (nonresponders, n = 11 [29.7%]) Δ: +1%‡ (nonresponders) 
 
  Nonresponders: <50% ↓ in transfusion need, or Hb ↑ <10 g/L 
Karimi et al78  163 TI 13.5 10 72 Baseline: 86.8 Nonsignificant changes TI: group 1 (n = 120) TD, group 2 (n = 16) TD [intermittent], and group 3 (n = 27) NTD 
Δ: +9.6† (group 2 + 3, 12 mo) 
 
 Group 1: 83 [69.2%] TD → NTD, 23 [19.2%] TD → 1 or 2 transfusions 
 Group 2: 14 [87.5%] TD → NTD 
Alebouyeh et al79  36 TM 16.3 20 >6 Baseline: 100 — TI: NTD 
Δ: +7 25 [69.4%] TM patients TD → NTD 
9 TI 14.7 20 34-58 Baseline: 93 —  
(median 40) Δ: +11 
Yavarian et al80  133 TM 17.1 10-15 24-60 Good responders: n = 81 [60.9%] — Good responders: TD → NTD (Hb > 95 g/L) 
(median 42) Moderate responders: n = 31 [23.3%] 
  Moderate responders: transfusion interval >6 mo (Hb 75 to 96 g/L) 
  Nonresponders: TD after 12 mo 
Bradai et al81  7 TM + TI 12 18.4 13-21 -Baseline: 45 Baseline: 90.9% TI: TD 
(median 19) Δ: +34 (TM) Δ: +6.8% 5 [71.4%] patients: TD → NTD 
-Baseline: 65 2 [28.6%] TD → 1 or 2 transfusions 
Δ: +40 (TI) 
de Paula et al82  4 TM 18 10->20 6-96 Δ: +30 in 1 patient after 3 mo, no change in 3 patients — TI: TD [intermittent] 
1 TM patient became NTD after 3 mo 
7 TI 35 10->20 6 Baseline: 77 Baseline: 44.9% ΔHb > 10 g/L noted in 3 TI patients at 6 mo, 1 patient showed further response at 12 mo, no additional responses noted after >12 mo 
Δ: +10† Δ: +12.3%† 
Choudhry et al83  15 TM 3-6 50 3 5-d courses Δ: +8‡ 2-fold rise in 8 [53.3%] patients Response continued for 6 mo in 9 [60%] patients 
Fucharoen et al49  13 Hb E/β-thalassemia 34 15 5 Baseline: 65 Baseline: 42% — 
Δ: +7.4† Δ: +32.5%† 
F cells: ↑ by 1/3 
ReferenceSampleAge (y)*HU dose (mg/kg per d)*Duration (mo)Total Hb (g/L)*Fetal Hb*Comments
Karimi et al65  126 TM 22.3 10 96-156 Baseline: 85-100 — TI: NTD or TD [intermittent] 
Final: ≥90 (n = 51 [40%])  TM: 86 [68.3%] TD → NTD, 25 [19.8%] TD → 1 or 2 transfusions 
Final: ≥80 to <90 (n = 44 [35%])  
Final: ≥70 to <80 (n = 16 [13%])  
Final: <70 (n = 15 [12%])  
106 TI 18.1 10 96-156 Δ: +≥20 (n = 12 [11%]) — 
Δ: +10 to <20 (n = 44 [42%]) 
Δ: +<10 (n = 47 [44%]) 
Δ: no change (n = 3 [3%]) 
Amoozgar et al66  33 TI 20 10 12 Baseline: 98.4 Baseline: 79.3 g/L TI: NTD or TD [intermittent] 
Δ: +13.4† Δ: +8.0 g/L‡ 
51 TI 17 None 12 Baseline: 92.8 — 
Δ: +4.7‡   
Ansari et al67  119 TM 2.6-25 16 24 -Baseline: 75 Baseline: 11.2% TI: NTD 
Δ: +1‡ (responders, n = 33 [27.7%]) Δ: +88.4% (responders) Responders: TD → NTD 
-Baseline: 82  Partial responders: >50% ↓ in transfusion need 
Δ: −14† (partial responders, n = 57 [47.9%])  
-Baseline: 79  Nonresponders: <50% ↓ in transfusion need 
Δ: −13† (nonresponders, n = 29 [24.4%])  
27 TI 3-13 16 24 Baseline: 67 Baseline: 98.5%  
Δ: +11† Δ: +1.4%  
Italia et al68  13 Hb E/β-thalassemia 8-34 15-20 17-23 -Baseline: 61 -Baseline: 22.3% Responders: TD → NTD 
(median 20) Δ: +11† (responders, n = 6 [46.2%]) Δ: +16%† (responders) Partial responders: ↓ in transfusion need (30% to 50%) 
-Baseline: 63 F cells: +25.8%† 
Δ: 0‡ (partial responders, n = 4 [30.8%]) -Baseline: 15.2% Nonresponders: no change in transfusion need 
-Baseline: 76 Δ: +16.6%‡ (partial responders) 
Δ: −12‡ (nonresponders, n = 3 [23.1%]) F cells: +18.5%‡ 
-Baseline: 2.9% 
Δ: +5.8%† (nonresponders) 
F cells: +13.3%† 
Karimi et al69  143 TI 21 10.7 18-120 Baseline: 74 — TI: NTD or TD 
   (median 68.4) Δ: +23†   
Rigano et al50  24 TI 37 14.6 12 Baseline: 78 Baseline: 46.5% TI: NTD 
Δ: +15† Δ: +10.7%† 17 patients with ΔHb > 10 g/L followed for >12 mo (mean: 68 mo); 9 maintained response, while 8 had reduction 
Ehsani et al70  16 TI 10.7 20 6 Δ: +16 Δ: +17 g/L TI: NTD 
Italia et al44  41 TM 12-28 15-20 20-24 -Baseline: 81 -Baseline: 5.4% TI: TD [intermittent] or TD 
Δ: −5‡ (partial responders, n = 13 [31.7%]) Δ: +32%† (partial responders) Responders: TD → NTD 
-Baseline: 76 F cells: +40.9%† Partial responders: >50% ↓ in transfusion need 
Δ: −5‡ (nonresponders, n = 28 [68.3%]) -Baseline: 3.7% 
Δ: +8.2%† (nonresponders) Dose increases to 30 mg/kg per day in nonresponders had no benefit 
F cells: +13.8%† 
38 TI 5-40 15-20 20-24 -Baseline: 76 -Baseline: 51.8%  
Δ: +15† (responders, n = 22 [57.9%]) Δ: +35.4%† (responders) 
-Baseline: 79 F cells: +27.4%† 
Δ: −2‡ (partial responders, n = 6 [15.8%]) -Baseline: 6.3% 
-Baseline: 63 Δ: +31.1%† (partial responders) 
Δ: −2‡ (nonresponders, n = 10 [26.3%]) F cells: +33.3%† 
-Baseline: 25.9% 
Δ: +20%† (nonresponders) 
F cells: +32.8%† 
Zamani et al71  49 TM 18.4 10 12 Baseline: 85.2 — Mean number of transfused units ↓ from 22.8 → 6.0† 
Δ: −0.7† 
12 [24.5%] became NTD 
 
Koren et al72  11 TM 18 10.9 5-60 Responders, n = 9 [81.8%] Baseline: 83% TI: NTD or TD [intermittent] 
(median 24) Δ: −1% (1 y) ‡, −5% (2 y) ‡ Responders: TD → NTD (maintaining an Hb of 70 g/L in TM and 60 g/L in TI) 
7 TI 18 10.9 36-96 -Baseline: 67 Baseline: 15%  
(median 60) Δ: +2 (5 TD, responders, n = 5 [100%]) Δ: +13%‡ (1 y), +8% (2 y) ‡ 
-Baseline: 66 
Δ: +18 (2 NTD) 
Mtvarelidze et al73  6 TM 9.8 15 60 Baseline: 94 Baseline: 23% 3 [50%] patients: TD → NTD 
Δ: +1 (12 mo), +3 (60 mo) Δ: +8.3% (12 mo), +20.4 (60 mo) 2 [33.3%] patients: ↓ in transfusion need after 1 y 
Ansari et al74  23 TM 8.7 16 24 Baseline: 86 — 42.8% ↓ in blood volume transfused 
Δ: −14 68.7% ↑ in transfusion interval 
Bradai et al75  45 TM 10 17.4 12 Δ: +15 (good responders, n = 20 [44.4%]) — TI: TD 
Δ: +7 (partial responders, n = 9 [20%]) Good responders: >70% ↓ in transfusion need 
Δ: +2 (nonresponders, n = 16 [35.6%]) 
 Partial responders: 40% to 70% ↓ in transfusion need 
9 TI 12.5 17 12 Δ: +37 (8 good responders [88.9%], 1 nonresponder [11.1%]) — Nonresponders: <40% ↓ in transfusion need 
Mancuso et al76  18 TI 37 14.6 12 Δ: +15† — TI: NTD 
11 patients with ΔHb > 10 g/L were followed for >12 mo (mean: 66 mo); 7 maintained response, while 4 had reduction 
Taher and Sheikh-Taha84  7 TI 24 10-20 6-46 Baseline: 70 — TI: NTD 
(median 12) Δ: +5 
Singer et al85  45 Hb E/β-thalassemia 13 18-20 24 Baseline: 68 Baseline: 29.8% Patients weaned off transfusions before study 
Δ: +6 Δ: +6.7% 
  16 [38%] patients had ΔHb > 10 g/L 
Dixit et al77  37 TM + TI 10 10->20 6 -Baseline: 65 -Baseline: 67% -TI: NTD, TD [intermittent], or TD 
Δ: +26† (major responders, n = 17 [45.9%]) Δ: +9%† (major responders) Major responders: TD → NTD (Hb > 80 g/L), or Hb ↑ >20 g/L 
-Baseline: 63 -Baseline: 70.2% 
Δ: +18† (minor responders, n = 9 [24.3%]) Δ: +8.5‡ (minor responders) Minor responders: TD → NTD (Hb < 80 g/L), >50% ↓ in transfusion need, or Hb ↑ 10 to 20 g/L 
-Baseline: 65 -Baseline: 40.9% 
Δ: +5† (nonresponders, n = 11 [29.7%]) Δ: +1%‡ (nonresponders) 
 
  Nonresponders: <50% ↓ in transfusion need, or Hb ↑ <10 g/L 
Karimi et al78  163 TI 13.5 10 72 Baseline: 86.8 Nonsignificant changes TI: group 1 (n = 120) TD, group 2 (n = 16) TD [intermittent], and group 3 (n = 27) NTD 
Δ: +9.6† (group 2 + 3, 12 mo) 
 
 Group 1: 83 [69.2%] TD → NTD, 23 [19.2%] TD → 1 or 2 transfusions 
 Group 2: 14 [87.5%] TD → NTD 
Alebouyeh et al79  36 TM 16.3 20 >6 Baseline: 100 — TI: NTD 
Δ: +7 25 [69.4%] TM patients TD → NTD 
9 TI 14.7 20 34-58 Baseline: 93 —  
(median 40) Δ: +11 
Yavarian et al80  133 TM 17.1 10-15 24-60 Good responders: n = 81 [60.9%] — Good responders: TD → NTD (Hb > 95 g/L) 
(median 42) Moderate responders: n = 31 [23.3%] 
  Moderate responders: transfusion interval >6 mo (Hb 75 to 96 g/L) 
  Nonresponders: TD after 12 mo 
Bradai et al81  7 TM + TI 12 18.4 13-21 -Baseline: 45 Baseline: 90.9% TI: TD 
(median 19) Δ: +34 (TM) Δ: +6.8% 5 [71.4%] patients: TD → NTD 
-Baseline: 65 2 [28.6%] TD → 1 or 2 transfusions 
Δ: +40 (TI) 
de Paula et al82  4 TM 18 10->20 6-96 Δ: +30 in 1 patient after 3 mo, no change in 3 patients — TI: TD [intermittent] 
1 TM patient became NTD after 3 mo 
7 TI 35 10->20 6 Baseline: 77 Baseline: 44.9% ΔHb > 10 g/L noted in 3 TI patients at 6 mo, 1 patient showed further response at 12 mo, no additional responses noted after >12 mo 
Δ: +10† Δ: +12.3%† 
Choudhry et al83  15 TM 3-6 50 3 5-d courses Δ: +8‡ 2-fold rise in 8 [53.3%] patients Response continued for 6 mo in 9 [60%] patients 
Fucharoen et al49  13 Hb E/β-thalassemia 34 15 5 Baseline: 65 Baseline: 42% — 
Δ: +7.4† Δ: +32.5%† 
F cells: ↑ by 1/3 

Hb, hemoglobin; HU, hydroxyurea; NTD, nontransfusion dependent; TD, transfusion dependent; TI, β-thalassemia intermedia; TM, β-thalassemia major.

*

All values represent the central tendency (mean or median) unless otherwise indicated. For HU dose, the fixed or actual mean/median maximal tolerated dose is indicated when reported; otherwise, the dosing scheme is described.

†

Statistically significant (P < .05).

‡

Statistically insignificant (P > .05).

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