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

Abstract

Summary: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 Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM).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. Bone Marrow Transplantation (2001) 27, 531-536. Keywords: thrombotic microangiopathy; lymphoma; chemotherapy The role of high-dose chemotherapy (HDC) with autologous stem cell support in relapsed non-Hodgkin's lymphoma (NHL) has been clearly demonstrated in patients with chemosensitive relapse. 1,2 However, NHL patients who do not achieve a first complete remission or experience early relapse still have a very poor prognosis even when HDC

Posttransplantation Thrombotic Thrombocytopenic Purpura: A Single-Center Experience and a Contemporary Review

“…52 The occurrence of TTP after autologous transplantation is consistent with primarily regimen-related toxicity or possibly infection. 36,37,53 Unlike the situation in idiopathic TTP, responses to PE are suboptimal, and posttransplantation TTP carries a poor prognosis (Table 1). 13,18,20 Most patients treated in our series showed some improvement in clinical and hematologic parameters in response to PE.…”

Influence of Alternative Tubulin Inhibitors on the Potency of Epirubicin-Immunochemotherapeutic Synthesized with an Ultra Violet Light-Activated Intermediate

“…Chemotherapeutic resistance is a particularly important development that hinders successful treatment of breast cancer because approximately 20–30% of all affected cases develop metastatic brain lesions which characteristically display moderate-to-high levels refractoriness to chemotherapeutic intervention (Honig et al, 2005). Despite the advantages of combination chemotherapy regimens, they still suffer from a high frequency of toxic sequelae that can limit the extent and duration of administration (Azad, Posadas et al, 2008; Balayssac et al, 2011; Ceresa & Cavaletti, 2011; Chang et al, 2001; Iarussi, Indolfi, Galderisi, & Bossone, 2000; Raschi et al, 2010; Scully & Lipshultz, 2007; Stavridi & Palmieri, 2008; Vantelon et al, 2001; Wachters, Van Der Graaf, & Groen, 2004). …”

Delayed Development of Hemolytic Anemia with Fragmented Red Blood Cells and Cardiac and Renal Impairments after High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoma

“…On the other hand, the risk of gemcitabine-associated TMA increases when the cumulative gemcitabine dose approaches 20,000 mg/m 2 and the number of doses exceeds 18, and TMA may develop after fewer cumulative doses and a smaller number of doses when the drug is used in combination with other cytotoxic drugs [23]. Taken together with the finding that 3 consecutive courses of HDC/AHSC led to TMA at an incidence of 3 out of 10 [15], it is possible that there is a threshold dose for TMA in each chemotherapeutic agent and this dose may be reduced in combination with multiple agents. …”

“…These patients showed the recovery of hematopoiesis and had no significant infection prior to the diagnosis of TMA. Regarding lymphoma, a pilot study to evaluate 3 sequential courses of HDC with AHSCT for refractory/relapsing aggressive lymphoma was stopped early due to the unexpectedly high occurrence rate (3 out of 10) of TMA [15]. In 1 patient, Coombs-negative HA-FrRBCs developed 5 months after the third HDC/AHSCT.…”

“…Although the safety of HDC/AHSCT has been confirmed in retrospective and prospective studies, TMA may develop after HDC/AHSCT, even though its incidence is markedly lower than that after allogeneic HSCT [14,15,16]. In contrast to allogeneic HSCT-associated TMA, the cause of HDC/AHSCT-associated TMA may be attributed to chemotherapeutic agents included in the HDC regimen.…”