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Published in Bobby Krishnachetty, Abdul Syed, Harriet Scott, Applied Anatomy for the FRCA, 2020
Bobby Krishnachetty, Abdul Syed, Harriet Scott
Capillary leak syndrome Hypotension, hypothermiaMassive blood transfusion and fluid resuscitationCoagulopathyPancreatitis
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Capillary leak syndrome has been reported after administration of G-CSF or derivatives and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.
Combinatorial Efficacy and Toxicity of an Engineered Toxin Body MT-3724 with Gemcitabine and Oxaliplatin in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Published in Cancer Investigation, 2023
Chenyu Lin, Ahmed Galal, David Rizzieri, Sant Chawla, Seung T. Lee, Angela Georgy, Kristina Dabovic, Thomas Strack, Matthew McKinney
Although six patients had been treated with the 75 µg/kg/dose of MT-3724 without developing capillary leak syndrome (CLS), in the expansion cohort of the phase I monotherapy trial, two of three patients experienced grade 2 CLS events at this dose (25,26). These patients had high body weights resulting in higher absolute doses of MT-3724 than administered previously. Capillary leak syndrome is a rare and potentially fatal inflammatory disorder characterized by weight gain, peripheral edema, hypoalbuminemia, hemoconcentration, and hypotension. The underlying pathophysiology of CLS is not well-understood, and proposed mechanisms include endothelial damage leading to capillary hyperpermeability, release of acute inflammatory cytokines, lymphokine-activated killer cell activation, and alterations in intercellular adhesions (27,28). CLS is often an important dose-limiting toxicity in clinical trials involving immunotoxin therapies, which may elicit an acute diffuse inflammatory response due to the intrinsic immunogenicity of the attached toxin moiety (27,29).
Moxetumomab pasudotox for the treatment of relapsed and/or refractory hairy cell leukemia
Published in Expert Review of Hematology, 2019
Iman Abou Dalle, Farhad Ravandi
The two distinct toxicity syndromes encountered with moxetumomab pasudotox are HUS and CLS. HUS is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia and renal failure [42]. Capillary leak syndrome is characterized by increased vascular permeability and leakage of fluids and proteins to the extravascular space, leading to peripheral edema, body weight gain of 5% or greater, hypoalbuminemia, and in severe cases, pulmonary and cardiovascular failure [43]. Overall, in the combined safety data of all patients treated with moxetumomab pasudotox, HUS was seen in 7% (9/129) of patients (grade 3, n = 4 (3%); and grade 4, n = 1 (0.8%)). CLS was seen in 34% (44/129) of patients (Grade 2, n = 30 (23%); grade 3, n = 2 (1.6%); grade 4, n = 3 (2%)) [44]. The pathogenic mechanism by which moxetumomab pasudotox induces HUS and/or CLS is not well understood. It was initially thought that it is related to targeting CD22, and by increasing the affinity to CD22, an increase in the HUS and CLS incidence was expected. However, during the dose escalation phase of moxetumomab pasudotox, there were no DLTs encountered, thus an alternate mechanism was investigated. The probable initiating factor for both syndromes could be a direct damage to vascular endothelial cells and red blood cells mediated by the Pseudomonas exotoxin [45].
Moxetumomab pasudotox for the treatment of hairy cell leukemia
Published in Expert Opinion on Biological Therapy, 2019
Agnieszka Janus, Tadeusz Robak
Twenty-eight patients aged 40 to 77 years with relapsed/refractory HCL were enrolled to a phase 1 dose-escalation trial: twenty-six of them with the classic form of HCL, and the remaining two with HCL-V (Table 1) [41]. In their previous treatment, all patients received one to seven cycles of purine analogs, 16 received rituximab and seven underwent splenectomy. Moxetumomab pasudotox was administered intravenously at doses of 5–50 µg/kg every other day for a total of three doses; this was repeated every four weeks, for 1–16 cycles. No dose-limited toxicity (DLT) was observed, no maximum tolerated dose (MTD) was established. Two patients experienced mild hemolytic uremic syndrome (HUS), which resolved after hydration and diuretics. Pulmonary embolism and pneumonia occurred in one patient with a history of stroke. One patient required treatment due to hypoxia and bronchospasm. The most common adverse events linked to the therapy were hypoalbuminemia (54% of cycles), elevated aminotransferase levels (38% of cycles), limb edema (25% of cycles), headache (13%) and hypotension (11% of cycles). Mild manifestations of capillary leak syndrome (CLS) were reported in 7% of cycles. No correlation was found between dose and toxicity level. The overall response rate was 86%, including 46% CRs and 39% partial responses (PRs). CRs were seen at the doses as low as 10 ug/kg [41].