MYOCARDITIS CAUSED BY GRANULOCYTE COLONY STIMULATING FACTOR ADMINISTRATION IN A HEALTHY HEMATOPOIETIC STEM CELLS DONOR: A CASE REPORT

Abstract Background Human granulocyte colony stimulating factor (G–CSF) is a glycoprotein promoting neutrophilic bone marrow production. Its recombinant form is used to decrease chemotherapy related infection incidence or for hematopoietic stem cells (HSCs) mobilization in allogenic transplantation. Its most common adverse reactions are musculoskeletal pain and cephalea, whereas the most severe ones are splenic rupture, anaphylaxis and acute respiratory distress syndrome; few aortitis cases have been reported either spontaneously resolved or faced with steroid therapy. One case of myocarditis secondary to G–CSF use has been reported, causing cardiogenic shock and requiring cardiopulmonary support. So, monitoring G–CSF therapy and its potential adverse events is pivotal in the clinical practice. Clinical Case A young 21–year–old man was selected as HSCs donor for allogenic transplantation. After laboratory and imaging exams, as transthoracic echocardiography (TTE) showing normal left ventricular (LV) systolic function, a bicuspid aortic valve with mild regurgitation and no pericardial effusion, the donor underwent human recombinant G–CSF stimulation at 10 ug/kg/die for five days with adequate collection of HSCs. After the apheresis, the donor got to the Emergency Room due to oppressive chest pain, denying any past gastrointestinal or respiratory infections. ECGs were negative and blood tests displayed increased Troponin values up to 54,5 ng/L and C–reactive protein up to 7,38 mg/L. TTE showed mild LV dilation (88ml/m2) with normal ejection fraction (EF 54%), no kinetic abnormalities or pericardial effusion. Coronary Angio–CT was negative, while Cardiac Magnetic Resonance revealed mild LV dilation (123ml/m2) with mild EF decrease (46%), diffuse hypokinesia and negative tissue characterization. After a multidisciplinary discussion with haematology department colleagues, a case of immune–mediated myocarditis provoked by G–CSF was hypothesised and the patient was discharged on the 7th day of hospitalization with negative blood tests and ECGs, with no drug therapy undertaken. Cardioimmunology follow–up visit implied TTE with evidence of preserved LVEF, mild LV dilation (80 ml/m2) and normal kinesis. Holter–ECG presented no arrhythmias and the anti–heart autoantibodies screening yielded negative results. Diagnosis of clinically suspected myocarditis was confirmed and intense physical exercise restriction was recommended untill next follow up visit.