A case of Alemtuzumab-induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes

A G Vakrakou,E Gialafos,M E Evangelopoulos,D Tzanetakos,L Stefanis,K Psarra,E Grigoriou,G Koutsis,J Tzartos,C Kilidireas,C Chrysovitsanou,A Dimitrakopoulos,S Valsami,M Anagnostouli,E Andreadou

doi:10.1186/s12883-018-1183-4

A G Vakrakou, E Gialafos + Show 13 more

Open Access

https://doi.org/10.1186/s12883-018-1183-4

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Abstract

BackgroundAlemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in Multiple Sclerosis (MS) patients compared to β-interferon. It acts against CD52, leading primarily to lymphopenia. Recent data have shown that mild neutropenia is observed in 16% of treated MS-patients whereas severe neutropenia occurred in 0.6%.Case presentationHerein, we present the case of a 34-year-old woman with relapsing-remitting MS, with a history of treatment with glatiramer acetate and natalizumab, who subsequently received Alemtuzumab (12 mg / 24 h × 5 days). 70-days after the last Alemtuzumab administration, the patient displayed neutropenia (500 neutrophils/μL) with virtual absence of B-cells (0.6% of total lymphocytes), low values of CD4-T-cells (6.6%) and predominance of CD8-T-cells (48%) and NK-cells (47%); while large granular lymphocytes (LGL) predominated in the blood-smear examination. Due to prolonged neutropenia (5-days) the patient was placed on low-dose corticosteroids leading to sustained remission.ConclusionThis is the first case of a patient with relapsing-remitting MS with neutropenia two months post-Alemtuzumab, with simultaneous presence of LGL cells in the blood and a robust therapeutic response to prednisolone. We recommend testing with a complete blood count every 15 days in the first 3 months after the 1st Alemtuzumab administration and searching for large granular lymphocytes cell expansion on microscopic examination of the peripheral blood if neutropenia develops.

Highlights

Alemtuzumab has been demonstrated to reduce the risks of relapse and accumulation of sustained disability in Multiple Sclerosis (MS) patients compared to β-interferon
This is the first case of a patient with relapsing-remitting MS with neutropenia two months postAlemtuzumab, with simultaneous presence of large granular lymphocytes (LGL) cells in the blood and a robust therapeutic response to prednisolone
Alemtuzumab is a humanized monoclonal antibody directed against CD52, a surface glycoprotein with poorly understood role, that mainly is expressed on lymphocytes (B and T cells) and to a lesser magnitude on monocytes, macrophages and eosinophil granulocytes [1]

Summary

Conclusion

This is the first case of a patient with relapsing-remitting MS with neutropenia two months postAlemtuzumab, with simultaneous presence of LGL cells in the blood and a robust therapeutic response to prednisolone. We recommend testing with a complete blood count every 15 days in the first 3 months after the 1st Alemtuzumab administration and searching for large granular lymphocytes cell expansion on microscopic examination of the peripheral blood if neutropenia develops

Findings

Background

Discussion and conclusions