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-dos e sequential chemotherapy regimen with peripheral blood stem cell (PBSC) su pport. Five treatment phases were scheduled: phase I (cyclophosphamide + et oposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cis platinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC i nfusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim), Ten, nin e, eight, six and four of the 10 patients received one, two, three, four an d five of the five scheduled phases of treatment, respectively. Four patien ts were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who complet ed all treatment phases, an additional case of TM was seen. In all three pa tients with TM, laboratory studies showed evidence of Coombs negative hemol ytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac fa ilure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.