Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy

Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non-Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support. Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and four of the 10 patients received one, two, three, four and five of the five scheduled phases of treatment, respectively. Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who completed all treatment phases, an additional case of TM was seen. In all three patients with TM, laboratory studies showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac failure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.