Gemcitabine-Associated Thrombotic Microangiopathy: Response to Complement Inhibition and Reinitiation of Gemcitabine

Turner, Jeffrey L.; Reardon, Joshua; Bekaii‐Saab, Tanios; Cataland, Spero R.; Arango, Matthew

doi:10.1016/j.clcc.2016.09.004

Cited by 20 publications

(22 citation statements)

References 17 publications

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“…After 2 months of treatment with gemcitabine, she did not show any recurrence of TMA. 45 The role of complement activation in the pathophysiology DI-TMA is not clear. Because therapy with eculizumab has only been reported for the treatment of gemcitabine-induced TMA, it is difficult to attribute complement dysregulation to the TMA induced by other drugs.…”

Section: Treatmentmentioning

confidence: 99%

None of the above: thrombotic microangiopathy beyond TTP and HUS

Masias

Vasu

Cataland

2017

Blood

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Acquired thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are appropriately at the top of a clinician’s differential when a patient presents with a clinical picture consistent with an acute thrombotic microangiopathy (TMA). However, there are several additional diagnoses that should be considered in patients presenting with an acute TMA, especially in patients with nondeficient ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity (>10%). An increased awareness of drug-induced TMA is also essential because the key to their diagnosis more often is an appropriately detailed medical history to inquire about potential exposures. Widespread inflammation and endothelial damage are central in the pathogenesis of the TMA, with the treatment directed at the underlying disease if possible. TMA presentations in the critically ill, drug-induced TMA, cancer-associated TMA, and hematopoietic transplant–associated TMA (TA-TMA) and their specific treatment, where applicable, will be discussed in this manuscript. A complete assessment of all the potential etiologies for the TMA findings including acquired TTP will allow for a more accurate diagnosis and prevent prolonged or inappropriate treatment with plasma exchange therapy when it is less likely to be successful.

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Section: Treatmentmentioning

confidence: 99%

None of the above: thrombotic microangiopathy beyond TTP and HUS

Masias

Vasu

Cataland

2017

Blood

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“…In the present cohort, five patients were treated with eculizumab, with one complete remission and three haematological remissions. Previous case series, including one from our group [30] reported good outcomes after eculizumab in the setting of G-TMA, with cases of complete remission [28,29]. Although none of these patients had a documented abnormality of CAP, deposits of C5b9 and C4d were documented on some renal biopsies from Age is expressed as median with interquartile ranges.…”

Section: Discussionmentioning

confidence: 95%

Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

Daviet

Rouby

Poullin

et al. 2018

Brit J Clinical Pharma

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Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine‐associated TMA (G‐TMA). Methods From 1998 to 2015, all cases of G‐TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G‐TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m–2. Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new‐onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G‐TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.

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Section: Drug-induced Tmamentioning

confidence: 99%

“…In some of these cases, eculizumab was stopped after as few as 2 doses, though some were treated for as long as 15 months [28]. As with aHUS, all published cases of dTMA treated with eculizumab found that hematologic recovery occurred rapidly (within weeks), while renal recovery often took months [28]. The criteria for stopping eculizumab in these cases are not consistently listed, but therapy was typically continued until substantial improvement in thrombocytopenia and anemia and diminished signs of hemolysis.…”

Section: Drug-induced Tmamentioning

confidence: 99%

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies

Olson

Sulpizio

et al. 2018

Am J Nephrol

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The terminal complement-inhibitor eculizumab has dramatically changed the management of patients with atypical hemolytic uremic syndrome (aHUS), and has also shown promise for treating certain forms of secondary HUS (sHUS), including that caused by drugs and solid-organ/hematopoietic stem cell transplant. While effective, eculizumab is costly and inconvenient. In this review, we evaluate the literature on eculizumab cessation in these diseases to better inform clinicians who consider stopping therapy. Reported relapse rates in aHUS after stopping eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and that patients who choose to stop should be closely monitored. In sHUS, relapse is rare, justifying short courses of eculizumab.

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Gemcitabine-Associated Thrombotic Microangiopathy: Response to Complement Inhibition and Reinitiation of Gemcitabine

Cited by 20 publications

References 17 publications

None of the above: thrombotic microangiopathy beyond TTP and HUS

None of the above: thrombotic microangiopathy beyond TTP and HUS

Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies

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