Purpose: Cyclophosphamide in monthly intravenous bolus is used to treat severe forms of systemic sclerosis with pulmonary involvement. Since 1996, cyclophosphamide therapeutic intensification with autologous haematopoietic stem cells transplantation allowed significant improvement in skin and functional scores in severe systemic sclerosis. Cyclophosphamide potential cardiotoxicity in this setting has been questioned.
Methods: To analyse cyclophosphamide potential cardiopulmonary toxicity (as graded with WHO classification), we retrospectively studied all severe systemic sclerosis patients treated with cyclophosphamide either during autologous haematopoietic stem cells transplantation procedure (group A) or intravenous cyclophosphamide (group B) recruited in 7 French centers volunteers for the study. Parameters to evaluate heart and lung functions at inclusion, then at last follow-up between 6 and 12 months after start of treatment, were compared using the Mann-Whitney test.
Results: (Mean+/-standard deviation): Groups A (N=14) and B (N=13) were similar at the beginning of the study in terms of skin, renal, heart and lung involvement. Cyclophosphamide total dose (/m(2)) received in group A was superior (P=0.02) to the one in group B. After respective follow-up of 10+/-2.8 (group A) and 9.9+/-2.7 (group B) months, cyclophosphamide cardio toxicity (group A: N=3; group B: N=2), evolution of the left ventricular ejection fraction and arterial and pulmonary pressures did not differ in the two groups.
Conclusion: In spite of higher cyclophosphamide doses during autologous haematopoietic stem cells transplantation than bolus treatment, cardiopulmonary toxicity appeared not increased. The ongoing European ASTIS trial will compare the respective benefits of these 2 cyclophosphamide regimens in severe Systemic sclerosis.