Trial of recombinant human erythropoietin: three patients with thalassemia intermedia [letter]

Olivieri, NF; Freedman, Mervin B.; Perrine, SP; Dover, GJ; Sheridan, B; Essentine, DL; Nagel, RL

doi:10.1182/blood.v80.12.3258.3258

Cited by 48 publications

(14 citation statements)

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“…Erythropoietin has also been tested for elevating Hb levels, but the results were not satisfactory and further development in this area was not pursued. 37 …”

Section: Nongenetic Factors Influencing the Rate Of Iron Absorption Amentioning

confidence: 99%

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Kontoghiorghe¹,

Kontoghiorghes²

2016

DDDT

131

152

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The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption.

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“…Erythropoietin has also been tested for elevating Hb levels, but the results were not satisfactory and further development in this area was not pursued. 37 …”

Section: Nongenetic Factors Influencing the Rate Of Iron Absorption Amentioning

confidence: 99%

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Kontoghiorghe¹,

Kontoghiorghes²

2016

DDDT

131

152

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“…Thus, in this study, the desired F-reticulocyte response in SS patients was only manifested in those patients receiving supplemented oral iron with the recombinant Epo. However, a recent preliminary trial (Olivieri et al, 1992) in three thalassaemic patients suggests that iron supplementation may not be required to obtain an increase in reticulocytes and Hct. Therefore controlled trials of Epo f o r a l iron in SS and thalassaemic patients will be required to throw more light on this problem (Sher et al, 1994).…”

Section: Endogenous Gene Activation: Modulation Of Existing Globin Gementioning

confidence: 99%

“…The first controlled trial of rHuEpO and HU did show slight improvement both in the quality and quantity of the newly formed RBC compared to the use of each of the treatment modalities alone (Aker et al, 1994;Rachmilewitz et aZ, 1991). In spite of these erythroid cells in culture (Fibach et al, 1993b), in several animal models and in patients with other genetic diseases (Dover et al, 1992). A recent trial with phenylbutyrate in sickle-cell patients has substantiated an effect of this agent in augmenting HbF levels in the haemoglobinopathies .…”

Section: Endogenous Gene Activation: Modulation Of Existing Globin Gementioning

confidence: 99%

Novel Treatment Options in the Severe Β‐globin Disorders

Rodgers¹,

Rachmilewitz²

1995

Br J Haematol

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“…Rachmilewitz thalassaemia. In patients with P-thalassaemia intermedia, two preliminary studies have been carried out (Rachmilewitz et al, 1991;Olivieri et al, 1992). In the first trial, three patients were treated with 500-1000 u/kg of rHuEPO administered intravenously twice a week over a period of 3 months.…”

mentioning

confidence: 99%

Sustained increase in haemoglobin and RBC following long‐term administration of recombinant human erythropoietin to patients with homozygous beta‐thalassaemia

Aker

Perry

et al. 1995

Br J Haematol

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Recombinant human erythropoietin (rHuEPO) was given subcutaneously three times per week in an escalating dose from 500 u/kg to 950 u/kg together with ferrous fumarate 305 mg and folic acid 5 mg/d, to 10 patients from four unrelated Arab families with homozygous beta-thalassaemia. Six splenectomized patients showed a mean (+/- standard error) increase in haemoglobin from 7.1 +/- 0.1 to 9.3 +/- 0.1 g/dl (P = 0.0001), in RBC from 4.0 to 5.0 x 10(12)/l (P = 0.0001) and in nucleated RBC from 32 +/- 7 x 10(10)/l to 82 +/- 6 x 10(10)/l while receiving 750 u/kg three times per week which persisted for 4-11 months. In two patients there was no need for further blood transfusions. In three out of four unsplenectomized patients there were no changes in Hb and RBC despite dose escalation. There were no significant changes in MVC, MCH and reticulocyte count, serum bilirubin, LDH, malonyldialdehyde (MDA) and vitamin E levels. After 13 weeks of rHuEPO there was a mean increase in the percentage of F cells from 31 +/- 10% to 86 +/- 6% (P < 0.003) in three splenectomized patients and in one unsplenectomized patient from 56.4% to 80% without changes in the levels of Hb F. Globin chain synthesis ratios did not change in four responding patients. Mean serum iron and transferrin saturation index did not change, whereas mean serum ferritin increased from 299 +/- 45 micrograms/l to 480 +/- 20 micrograms/l (P < 0.001). In seven responding patients an accelerated linear growth was indicated by positive changes in height standard deviation score for chronological age. Side-effects were minimal throughout the treatment period.

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Trial of recombinant human erythropoietin: three patients with thalassemia intermedia [letter]

Cited by 48 publications

References 0 publications

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Novel Treatment Options in the Severe Β‐globin Disorders

Sustained increase in haemoglobin and RBC following long‐term administration of recombinant human erythropoietin to patients with homozygous beta‐thalassaemia

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