Systematic Review: Hydroxyurea for the Treatment of Adults with Sickle Cell Disease

Lanzkron, Sophie; Strouse, John J.; Wilson, Renée F; Beach, Mary Catherine; Haywood, Carlton; Park, HaeSong; Witkop, Catherine; Bass, Eric B.; Segal, Jodi B

doi:10.7326/0003-4819-148-12-200806170-00221

Cited by 238 publications

(182 citation statements)

References 77 publications

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“…[72][73][74][75] In addition, several retrospective studies did not find an increased risk of AL in PV and ET treated with HU alone, [76][77][78] and similar conclusions were drawn from a recent meta-analysis of HU therapy in sickle cell anemia. 79 Still, very long-term results of prospective studies in HU-treated MPN patients with more than 10 years of follow-up showed a cumulative incidence of AL/MDS of more than 10% beyond 12 years of follow-up, suggesting that the risk of leukemic evolution could be higher than reported earlier in studies with shorter follow-up. 80 The relative contribution of HU and of a natural, very long-term evolution of the disease in the pathogenesis of those late AL/MDS remains unclear.…”

Section: Ifn-a and Leukemic Evolutionmentioning

confidence: 54%

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

2008

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Interferon (IFN) was the first cytokine discovered 50 years ago, with a wide range of biological properties, including immunomodulatory, proapoptotic and antiangiogenic activities, that rapidly raised interest in its therapeutic use in malignancies. IFN-receptor characterization was also pivotal in the discovery of the JAK/STAT signaling pathway. Among the large IFN family, mainly one of the type I IFN, IFN-a2, is used in therapy. Many clinical trials have shown remarkable efficacy of IFN-a in bcr-abl-negative myeloproliferative neoplasms (MPNs), especially polycythemia vera (PV), and essential thrombocythemia (ET). IFN-a induces about 80% of hematological responses in those diseases and is able to reduce splenomegaly, as well as relieve pruritus and other constitutional symptoms. Yet its use was limited by toxicity, leading to early treatment discontinuation in about 20% of the patients. However, its lack of leukemogenic potential and its possible use during pregnancy have already made IFN-a the drug of choice for younger MPN patients. In addition, several studies have shown a probably selective effect of IFN-a on PV and ET clones, as shown by cytogenetic remissions, reversions to polyclonal hematopoiesis, and more recently by induction of JAK2V617F complete molecular remissions in PV which may widen the indications of IFN-a in JAK2-mutated MPN.

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Section: Ifn-a and Leukemic Evolutionmentioning

confidence: 54%

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

2008

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“…Among chemotherapy agents, Hydroxyurea (HU) is commonly used as an anti-cancer agent [4]. For instance, HU is an effective reagent which was widely applied for treatment of acute angina, breast cancer, several hematological malignancies including chronic myelogenous leukemia (CML), sickle cell anemia, myeloproliferative disorders, and other known cancers previously [5][6][7][8][9]. In addition to its beneficial properties several disadvantages and side effects such as skin disorders were reported to be associated HU in consumers [10,11].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of the Efficacy of Liposomal and Pegylated Liposomal Hydroxyurea

et al. 2013

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Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this study a mixture of phosphatidylcholine and cholesterol was made up and HU was added to the resultant mixture, was then pegylated using Polyethylene Glycol 2000 to increase resistance, applicability and solubility. The mean diameters of nanoliposomal and pegylated nanoliposomal HU were measured by Zeta sizer device and obtained about 402.5 and 338.2 nm. The efficiency of non-pegylated and pegylated liposomal HU was 70.8 and 64.2, respectively. Releasing HU in both formulations was estimated about 25.8 and 21.7 %. Also, this study investigated the cytotoxicity effect of nanoliposomal and pegylated nanoliposomal HU using MTT assay. Results of this investigation showed that the cytotoxic properties of pegylated HU was 3.6 % more than those non-pegylated form, while was 38.93 % more than ordinary from of HU. This study showed that the stability, releasing pattern and cytotoxicity of the pegylated nanoliposomal HU is better than that of nanoliposomal HU.

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“…Several clinical trials and observational studies have documented the efficacy of HU among adults and children with SCD [11][12][13][14][15][16][17][18][19]. Use of HU among children, which is off-label, has been shown to reduce episodes of vaso-occlusive pain, acute chest syndrome, and the need for blood transfusions [15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea

Tripathi¹,

Jerrell²,

Stallworth³

2010

Pediatric Blood & Cancer

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BackgroundMore evidence of the safety and effectiveness of hydroxyurea (HU) in community‐based cohorts of pediatric patients with sickle cell disease (SCD) are needed. The association of HU with organ‐specific clinical complications and adverse events is examined herein.MethodsMedicaid medical and pharmacy claims for the calendar years January 1996 through December 2006 were used to identify a cohort of children and adolescent patients (ages 17 and under) with a diagnosis of SCD (homozygous) who were treated with HU and developed disparate complications or adverse side effects. Of the 2,194 pediatric SCD patients identified, 175 (8%) were treated with HU. Incidence density matching (1 case: 2 controls) was used to select the control group on age, gender, ethnicity, time in the Medicaid data set, and baseline severity resulting in a total study cohort of 523 cases.ResultsOrgan‐specific complications were more likely in the HU‐treated group compared to non‐HU‐treated group: cardiovascular complications (odds ratio [OR] = 3.15; confidence interval [CI] = 1.97–5.03); hepatic complications (OR 5.41; CI = 3.54–8.27); renal complications (OR 5.09; CI 3.37–7.67); and pulmonary complications (OR 4.07; CI 1.88–8.79). Many of these conditions began developing before HU was prescribed. Developing three or more complications was also more likely in the HU group (27.4% vs. 7.0%, P < 0.0001).ConclusionsExtending previous findings to routine practice settings, HU is being administered to the most severely ill children with SCD, many of whom had already started to develop organ‐specific complications, but it is not associated with development of serious adverse events. Pediatr Blood Cancer. 2010;56:90–94. © 2010 Wiley‐Liss, Inc.

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Systematic Review: Hydroxyurea for the Treatment of Adults with Sickle Cell Disease

Abstract: Hydroxyurea has demonstrated efficacy in adults with sickle cell disease. The paucity of long-term studies limits conclusions about toxicity.

Cited by 238 publications

References 77 publications

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

Interferon-α therapy in bcr-abl-negative myeloproliferative neoplasms

In Vitro Evaluation of the Efficacy of Liposomal and Pegylated Liposomal Hydroxyurea

Clinical complications in severe pediatric sickle cell disease and the impact of hydroxyurea

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