Autoimmune thyroid disease following alemtuzumab therapy and hematopoietic cell transplantation in pediatric patients with sickle cell disease

Williams, Kristen M.; Dietzen, Danielle; Hassoun, Abeer; Fennoy, Ilene; Bhatia, Monica

doi:10.1002/pbc.25102

Cited by 14 publications

(12 citation statements)

References 21 publications

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“…Alemtuzumab‐induced lymphopenia, with decreased CD4 + CD25 + regulatory T cells, may predispose to the development of autoimmunity. Autoimmune disease has been described after alemtuzumab administration for MS, rheumatic diseases, and post‐HCT . Many of the published cases have been in the MS population involving autoimmune thyroiditis and immune thrombocytopenic purpura .…”

Section: Safety and Toxicitiesmentioning

confidence: 99%

Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review

Guilcher

Shah

Shenoy

2018

Pediatric Transplantation

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Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non-malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non-malignant disease, allowing for expanded access to curative HCT therapy.

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Section: Safety and Toxicitiesmentioning

confidence: 99%

Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review

Guilcher

Shah

Shenoy

2018

Pediatric Transplantation

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“…The mechanisms behind it are still uncertain, but it seems that thyroid dysfunction occurring after alemtuzumab therapy is an example of acquired autoimmunity . The study of Cox et al.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms behind it are still uncertain, but it seems that thyroid dysfunction occurring after alemtuzumab therapy is an example of acquired autoimmunity [6,12]. The study of Cox et al showed that after an initial depletion of lymphocytes, the B lymphocytes recovered earlier than T lymphocytes [14], making the patients more susceptible to autoimmunity [4,9].…”

Section: Discussionmentioning

confidence: 99%

Graves’ orbitopathy after allogeneic bone marrow transplantation in a patient with Fanconi anemia – side effect of alemtuzumab therapy?

Cima

Lambrescu

Stejereanu

et al. 2018

Clinical Case Reports

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“…Alemtuzumab treatment is associated with an increased risk for the development of autoimmune diseases, for this reason a regular monitoring is indicated to allow for an early recognition and thereby early treatment of these diseases [10,17,19,[54][55][56][57]. Most of the autoimmune phenomena have a beneficial prognosis if they are identified early and anti-inflammatory treatment is started early.…”

Section: Post-infusion Monitoringmentioning

confidence: 99%

Hands on Alemtuzumab-experience from clinical practice: whom and how to treat

Hassoun

Eisele

Thomas

et al. 2016

Mult Scler Demyelinating Disord

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Alemtuzumab is a monoclonal antibody, which was recently approved for the treatment of active relapsing remitting multiple sclerosis. Its main mechanism of action is based on targeting CD52, an antigen of unknown function which is found on B and T lymphocytes, leading to depletion followed by repopulation of these cells. The high efficacy of Alemtuzumab in controlling relapsing remitting MS has been shown in several clinical trials. This new therapy approach is associated with a specific side effects profile requiring regular longterm monitoring. The most important side effects are infusion-associated reactions, a slight increase of infections as well as autoimmune events in almost one third of treated patients. Based on two years of clinical experience in Germany, this review covers the first steps with the careful patient selection to be treated with Alemtuzumab over the preparation steps and the infusion courses up to the longterm monitoring after Alemtuzumab treatment.

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Autoimmune thyroid disease following alemtuzumab therapy and hematopoietic cell transplantation in pediatric patients with sickle cell disease

Cited by 14 publications

References 21 publications

Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review

Principles of alemtuzumab immunoablation in hematopoietic cell transplantation for non‐malignant diseases in children: A review

Graves’ orbitopathy after allogeneic bone marrow transplantation in a patient with Fanconi anemia – side effect of alemtuzumab therapy?

Hands on Alemtuzumab-experience from clinical practice: whom and how to treat

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