Maria Eva Mingot-Castellano
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Dana Diaz-Canales
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Fernando Fernandez-Fuertes
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Maria Perera-Alvarez
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Isabel Caparros-Miranda
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...
Rationale and Objectives
Thrombopoietin analogues (TPOa) are an effective alternative of treatment in patients with refractary primary immune thrombocytopenia (ITP) or chronic ITP patients with esplenectomy contraindication. Although this is their ITP indication, there are other clinical situations in day by day ITP patients clinical management in where these drugs are being used off label. We describe the treatment profile, efficacy and safety of TPOa in ITP patients in ours centers.
Material and Methods
ITP patients diagnosed and treated with TPOa between March 2009 and May 2013 in five centers. The study variables were: age, sex, ITP status and bleeding profile, treatment lines before TPOa, reason to use them, baseline platelet and hemoglobin, response rate, time to response, treatment duration, bleeding and adverse events.
Results
We analyze 62 patients (35 women), median age 51.5 years-old (10-88 years old). 32.5% of patients present refractory chronic ITP, 51% non splenectomized chronic ITP, 10% persistent and 7.5% recently diagnosed ITP. 50% receive 3 or more treatment lines before TPOa. 8 patients receive treatment because of surgery, chemotherapy or radiotherapy (1 newly diagnosed, 1 persistent and 6 chronic non splenectomized ITP). The rest are treated because of bleeding and/or thrombocytopenia severity. Reasons to non splenectomize patients are comorbidities (52.8%), patient refusal (24.5%) or non chronic ITP criteria.
Median follow-up of TPOa treatment is 75 weeks (range 3-215 weeks), 91%. response rate. Median time to reach platelet count higher than 30x10e9/L is 2 weeks (1-22 weeks). Mean stable dose: eltrombopag 48.5+/-17mg/day and Romiplostin 3.4 +/-2.64mcg/kg/week with no difference between splenectomized and non splenectomized patients. 67% of chronic ITP patients present an stable response. 37% of patients require resque treatment during the follow-up. 6 (12%) patients with chronic ITP have discontinued TPOa after 6 to 24 months and they stay in response. 24 patients received only romiplostin, 22 only eltrombopag and 16 patients have been treated with the two available TPOa. One patient did not respond to any of them, another responded to romiplostin and not to eltrombopag, two to eltrombopag and not to romiplostin and the remaining 12 respond to both.
82% of patients present no bleeding event during TPOa treatment. 6 patients receive secondary prophylaxis with anticoagulants drugs and other 6 ones with antiplatelet during TPOa treatment with no haemorragic problems. In the 40 romiplostin treatments, the most common side effect was headache. We find only one case of transient elevation of transaminases among the 38 eltrombopag treatments. In 57 patients bone marrow aspirate was performed before TPOa indication, only 26 bone marrow biopsy were done. In two of these patients are described reticulin fibrosis grade 1 before treatment. No information on subsequent tests. We describe three thromboembolic events. One pulmonary embolism (PE) in a woman with vascular risk factors and history of lung cancer. The other two events were lower limbs venous thrombosis in young subjects with no risk factors or abnormally high platelet counts. Diagnosis of 1 aplastic anemia and 1 myeloma during treatment with TPOa. Four exitus, 2 intracranial bleedings, 1 PE and 1 of unknown cause. 24% of patients treated with romiplostin are on out-hospital treatmen, in most cases for reasons not related to patient autoself-treatment capacity.
Conclusions
New thrombopoietic agents are indicated in refractory chronic ITP or chronic ITP patients with splenectomy contraindications. There are other situations in ITP evolution where they could be useful. These off label situations can become even more prevalent than so far established indication. In our experience, these drugs are effective and safe in these others conditions but treatment should be individualized based on patient needs and comorbidities. Lack of response to one TPOa agent does not mean the other one inefficiency.
Disclosures:
No relevant conflicts of interest to declare.
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