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      Atypical Evolution of Secondary Hemolytic Uremic Syndrome Defined as Paraneoplastic Syndrome under Eculizumab and Palbociclib Therapies

      case-report

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          Abstract

          Thrombotic microangiopathy (TMA) is most of the time caused by thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. A 60-year-old female was diagnosed in 2014 with mammary breast adenocarcinoma treated by several-line therapy: mastectomy, docetaxel, cyclophosphamide, radiotherapy, doxorubicine, and capecitabine. By mid-November, the patient was admitted to the hospital with regenerative, mechanical, and hemolytic anemia, schistocytes at 3%, and thrombopenia (99 G/L), associated with high blood transfusion requirement. After 9 sessions of plasmapheresis, there was no significant improvement in the biological parameters, nor after 2 cycles of paclitaxel. The patient was then treated with eculizumab during 4 weeks, with a slight reduction in blood requirement, and simultaneously with palbociclib. Since being treated with palpociclib, she had a great reduction in blood requirement and a good clinical condition. To conclude, we reported an initial moderate improvement of paraneoplasm-related TMA syndrome under eculizumab therapy with a slight reduction in red blood cell requirement; however, palbociclib therapy achieved a very good response with a dramatic reduction in red blood cell requirement.

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          Most cited references13

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          An international consensus approach to the management of atypical hemolytic uremic syndrome in children.

          Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.
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            Thrombotic microangiopathy, cancer, and cancer drugs.

            Thrombotic microangiopathy (TMA) is a complication that can develop directly from certain malignancies, but more often results from anticancer therapy. Currently, the incidence of cancer drug-induced TMA during the last few decades is >15%, primarily due to the introduction of anti-vascular endothelial growth factor (VEGF) agents. It is important for clinicians to understand the potential causes of cancer drug-induced TMA to facilitate successful diagnosis and treatment. In general, cancer drug-induced TMA can be classified into 2 types. Type I cancer drug-induced TMA includes chemotherapy regimens (ie, mitomycin C) that can potentially promote long-term kidney injury, as well as increased morbidity and mortality. Type II cancer drug-induced TMA includes anti-VEGF agents that are not typically associated with cumulative dose-dependent cell damage. In addition, functional recovery of kidney function often occurs after drug interruption, assuming a type I agent was not given prior to or during therapy. There are no randomized controlled trials to provide physician guidance in the management of TMA. However, previously accumulated information and research suggest that endothelial cell damage has an underlying immunologic basis. Based on this, the emerging trend includes the use of immunosuppressive agents if a refractory or relapsing clinical course that does not respond to plasmapheresis and steroids is observed.
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              Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors

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                Author and article information

                Journal
                CRO
                CRO
                10.1159/issn.1662-6575
                Case Reports in Oncology
                S. Karger AG
                1662-6575
                2021
                January - April 2021
                12 April 2021
                : 14
                : 1
                : 676-680
                Affiliations
                [_a] aDepartment of Clinical Pharmacy, Grenoble Alpes University Hospital, Grenoble, France
                [_b] bNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, Grenoble Alpes University Hospital, Grenoble, France
                [_c] cMedical Intensive Care Unit, Rouen University Hospital, Rouen, France
                [_d] dCentre de référence des microangiopathies thrombotiques (CNR-MAT), AP-HP, Paris, France
                [_e] eGrenoble Alpes University, Grenoble, France
                [_f] fGrenoble Alpes University, CNRS TIMC-IMAG, UMR 5525, Grenoble, France
                Article
                514982 Case Rep Oncol 2021;14:676–680
                10.1159/000514982
                8077600
                4d42332b-0e06-481f-bb52-317919a31fd4
                © 2021 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 01 February 2021
                : 02 February 2021
                Page count
                Figures: 2, Pages: 5
                Categories
                Case Report

                Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Atypical hemolytic uremic syndrome,Palbociclib,Breast cancer,Complement,Eculizumab,Thrombotic microangiopathy,Metastases

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