Fucharoen S, Siritanaratkul N, Winichagoon P, Chowthaworn J, Siriboon W, Muangsup W, Chaicharoen S, Poolsup N, Chindavijak B, Pootrakul P, Piankijagum A, Schechter A N, Rodgers G P
Department of Medicine, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand.
Blood. 1996 Feb 1;87(3):887-92.
Hydroxyurea (HU) is one of several agents that have been shown to enhance hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful as a therapy for beta-globinopathies. However, limited information exists on the effects of HU in patients with thalassemia. Accordingly, we examined the hematologic effects of orally administered HU in 13 patients with beta-thalassemia/Hb E, including four patients who had been splenectomized. These patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5 months and were observed in the outpatient hematology clinic every 2 to 4 weeks. Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, G gamma:A gamma and alpha:non-alpha globin biosynthetic ratios were evaluated before and during treatment. Almost all patients responded with an average increase of 33% in Hb F levels, from a mean (+/- SD) of 42% +/- 11% to 56% +/- 8% (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9% to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/- SD) of 18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but statistically significant increase in hemoglobin levels and an improved balance in alpha:non-alpha globin chains ratios. The side effects were minimal in most patients, although these patients tended to tolerate a lower dose of HU before significant myelosuppression than has been our previous experience in sickle cell disease. One splenectomized patient died of sepsis during the trial. We conclude that increased Hb F production in beta-thalassemia/Hb E patients, with an improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness of erythropoiesis, can be achieved using HU. Longer trials of HU in this population, including at other doses and in combination with other agents, appear warranted.
羟基脲（HU）是已被证明可提高镰状细胞病患者血红蛋白（Hb）F水平的几种药物之一，可能对β地中海贫血有治疗作用。然而，关于HU对地中海贫血患者影响的信息有限。因此，我们研究了口服HU对13例β地中海贫血/Hb E患者的血液学影响，其中包括4例已行脾切除术的患者。这些患者接受递增剂量（最终范围为10至20mg/kg/d）治疗5个月，每2至4周在门诊血液科进行观察。在治疗前和治疗期间评估全血细胞计数，包括网织红细胞计数、Hb E和Hb F含量、Gγ:Aγ和α:非α珠蛋白生物合成比率。几乎所有患者均有反应，Hb F水平平均升高33%，从平均（±标准差）42%±11%升至56%±8%（P<.0001），Hb E百分比相应从59%±9%降至49%±8%（P<.001）。网织红细胞增多从平均（±标准差）18.0%±15.6%降至11.7%±9.1%（P<.05）；血红蛋白水平也有轻微（10%）但具有统计学意义的升高，α:非α珠蛋白链比率得到改善。大多数患者的副作用极小，尽管与我们之前在镰状细胞病中的经验相比，这些患者在出现明显骨髓抑制之前往往只能耐受较低剂量的HU。1例脾切除患者在试验期间死于败血症。我们得出结论，使用HU可使β地中海贫血/Hb E患者的Hb F生成增加，α:非α珠蛋白比率得到改善，红细胞生成的有效性可能也会提高。对该人群进行更长时间的HU试验，包括使用其他剂量以及与其他药物联合使用，似乎是有必要的。
