PB1867 USE OF THERAPY WITH COMPLEMENT INHIBITOR AND THROMBOPOIETIN RECEPTOR AGONISTS IN TREATMENT OF PATIENT WITH SAA/PNH. CLINICAL CASE.
Authors: Shilova E. , Glazanova T. , Chubukina Z. , Zenina M. , Romanenko N. , Khorsheva I. , Voloshin S. 
Published: June 2019

Background:

Aplastic anemia (AA) is severe blood system disease, in which more than half of patients may have PNH clone, and there may occur associated variants AA with PNH (AA/PNH). The most frequently observed is the development of classical hemolytic PNH at AA remission, but possibly a combination of the two diseases. For such cases, there is a positive experience of AA combined treatment with immunosupressive therapy (IST) and targeted therapy using complement activation inhibitors. With resistant AA a therapeutic optionis possible using thrombopoietin receptor agonists.

Aims:

To treat of patient with SAA/PNH in absence of possibility of full use of IST

Methods:

A clinical observation of a 53‐year‐old female with AA/PNH in the course of the disease is presented. Since 1994 patient, aged 53 yrs, has been under our supervision. The diagnosis was established according to a comprehensive examination, with severity determination in accordance to international criteria. The examination used morphological, histological, immunological (including highly sensitive flow cytometry), biochemical methods. No compatible donor for bone marrow transplantation was found. Anti‐lymphocyte globulin (ALG), cyclosporin‐A (CyA), Eculizumab and thrombopoietin receptor agonists were used in treatment.

Results:

ALG and cyclosporine treatment gave only a temporary effect – an improvement in hemogram parameters and a reduction in transfusion dependence. CyA doses were reduced (about 3 mg per day) due to adverse effects. The possibilities of active IST were also limited by comorbidities, including chronic hepatitis B. Since 1999, signs of chronic intravascular hemolysis and hemolytic crises have been observed. Flow cytometry have detected PNH clone. Subsequently, according to ICNN protocol testing data, from 2011 to the present, the clone size was determined 96‐99% with a predominance of type III erythrocytes. According to repeated bone marrow assessments, severe aplasia with pancytopenia in the peripheral blood was maintained. Anemia persisted up to 65 g/dL with transfusion dependence (up to 12‐16 doses of red blood cells per year), leukopenia within 0.9‐1.5 x109/l and thrombocytopenia 5‐15 x109/l with cutaneous hemorrhagic syndrome. On 2013, after vaccination with meningococcal vaccine, Eculizumab treatment was started according to the standard scheme with achievement of an adequate control of hemolysis. Clinical manifestations of hemolysis are absent; the level of LDH does not exceed 1.5 ULN. Therapy continues to the present. Until 2015, CyA therapy was periodically resumed due to the persistence of SAA criteria. In 2013‐2015 the patient additionally received thrombopoetin agonist therapy: Romiplostimum (4‐6 ug/kg once a week) with breaks every 3‐4 months. Two months after the start of therapy, a clinical effect was obtained – a decrease in hemorrhagic syndrome. After 3 months, there was a trend towards an increase in platelet levels. At present, severe leukopenia (1.0 – 2.2 x109/l) and neutropenia (0.5‐0.7x109/l) persist. At the same time, the platelet level is 30‐70 x109/l without spontaneous hemorrhages, since January 2018 the patient does not receive blood transfusions and hemoglobin stays at 10.2‐11.0 g/dL. Also there has been a significant improvement in the quality of life.

Summary/Conclusion:

This case demonstrates the possibility of a significant improvement in the course of sAA/PNH (including quality of life) in the absence of a sufficient effect of IST, but adequate target control of hemolysis and the use of thrombopoietin receptor agonists.