Doxycycline for haematopoietic stem cell transplantation-related thrombotic microangiopathy

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a devastating consequence of allogeneic haematopoietic stem cell transplantation (HSCT) with a mortality rate of 60–90%. None of the interventions used, as used up till now in idiopathic thrombotic thrombocytopaenic purpura (TTP) (fresh frozen plasma transfusion, plasma exchange and steroids), were effective to treat TA-TMA [1,2]. We report a dramatic improvement of TA-TMA in two HSCT patients [conditioning, cyclophosphamide, total body irradiation, graft-versus-host disease (GVHD) prophylaxis] using doxycycline. A 36-year-old woman with Hodgkin's lymphoma received an allogeneic HSCT in December 2002. Twelve months later, she developed a biopsy-proven TMA (proteinuria, 3 g/day, microscopic haematuria, oliguric acute renal failure with creatinine level at 680 µmol/L; haemoglobin Hb, 6.3 g/dL; schistocytes; platelet count, 35 × 109/L; LDH, 1754 IU/L). The serum complement proteins were at normal levels, no mutations of the membrane cofactor protein were found and a plasma ADAMTS13 activity was found at 40%. Steroids, plasma exchange, fresh frozen plasma transfusion, vincristine and haemodialysis were tried with a partial response (haemoglobin, 7.3 g/dL, platelet 70 000/mm3 both after treatment). Doxycycline 200 mg daily was added for a suspected gastrointestinal Bartonella infection. Within two months, haemoglobin and platelet count rose without transfusion to 10.8 g/dL and 234 000/mm3, respectively. Despite improvement of haematological parameters, the patient remained dialysis-dependent. The second patient had a similar haematologic disease and course under doxycycline prescribed for a bartholinitis. Five patients with TTP and Bartonella-like erythrocyte inclusions, successfully treated with doxycycline, experienced recurrence of their TTP following cessation of treatment [3]. TA-TMA has a multi-factorial aetiology of endothelial damage. Doxycycline targeting the adherens junction on endothelial cells prevents vascular hyperpermeability [4]. Doxycycline as a potential treatment of TA-TMA warrants further studies. Conflict of interest statement. None declared.