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Published in: BMC Neurology 1/2018

Open Access 01-12-2018 | Case report

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

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

Published in: BMC Neurology | Issue 1/2018

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Abstract

Background

Alemtuzumab 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 presentation

Herein, 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.

Conclusion

This 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.
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Literature
1.
go back to reference Ruck T, Bittner S, Wiendl H, Meuth SG. Alemtuzumab in multiple sclerosis: mechanism of action and beyond. Int J Mol Sci. 2015;16(7):16414–39.CrossRef Ruck T, Bittner S, Wiendl H, Meuth SG. Alemtuzumab in multiple sclerosis: mechanism of action and beyond. Int J Mol Sci. 2015;16(7):16414–39.CrossRef
2.
go back to reference Ambrose LR, Morel AS, Warrens AN. Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab. Blood. 2009;114(14):3052–5.CrossRef Ambrose LR, Morel AS, Warrens AN. Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab. Blood. 2009;114(14):3052–5.CrossRef
3.
go back to reference Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet (London England). 2012;380(9856):1819–28.CrossRef Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet (London England). 2012;380(9856):1819–28.CrossRef
4.
go back to reference Baker D, Giovannoni G, Schmierer K. Marked neutropenia: significant but rare in people with multiple sclerosis after alemtuzumab treatment. Mult Scler Relat Disord. 2017;18:181–3.CrossRef Baker D, Giovannoni G, Schmierer K. Marked neutropenia: significant but rare in people with multiple sclerosis after alemtuzumab treatment. Mult Scler Relat Disord. 2017;18:181–3.CrossRef
5.
go back to reference Gaitan MI, Ysrraelit MC, Correale J. Neutropenia in patients with multiple sclerosis treated with Alemtuzumab. JAMA Neurol. 2017;74(9):1143–4.CrossRef Gaitan MI, Ysrraelit MC, Correale J. Neutropenia in patients with multiple sclerosis treated with Alemtuzumab. JAMA Neurol. 2017;74(9):1143–4.CrossRef
6.
go back to reference Galgani S, Prosperini L, Haggiag S, Tortorella C, Gasperini C. Early transient asymptomatic neutropenia associated with alemtuzumab treatment in multiple sclerosis: a case report. J Neurol. 2018;265(9):2152–3.CrossRef Galgani S, Prosperini L, Haggiag S, Tortorella C, Gasperini C. Early transient asymptomatic neutropenia associated with alemtuzumab treatment in multiple sclerosis: a case report. J Neurol. 2018;265(9):2152–3.CrossRef
8.
go back to reference Sauer EM, Schliep S, Manger B, Lee DH, Linker RA. Microscopic polyangiitis after alemtuzumab treatment in relapsing-remitting MS. Neurol(R) Neuroimmunology Neuroinflammation. 2018;5(5):e488.CrossRef Sauer EM, Schliep S, Manger B, Lee DH, Linker RA. Microscopic polyangiitis after alemtuzumab treatment in relapsing-remitting MS. Neurol(R) Neuroimmunology Neuroinflammation. 2018;5(5):e488.CrossRef
9.
go back to reference Willis MD, Harding KE, Pickersgill TP, Wardle M, Pearson OR, Scolding NJ, Robertson NP. Alemtuzumab for multiple sclerosis: long term follow-up in a multi-Centre cohort. Mult Scler (Houndmills, Basingstoke, England). 2016;22(9):1215–23.CrossRef Willis MD, Harding KE, Pickersgill TP, Wardle M, Pearson OR, Scolding NJ, Robertson NP. Alemtuzumab for multiple sclerosis: long term follow-up in a multi-Centre cohort. Mult Scler (Houndmills, Basingstoke, England). 2016;22(9):1215–23.CrossRef
10.
go back to reference O'Malley DP. T-cell large granular leukemia and related proliferations. Am J Clin Pathol. 2007;127(6):850–9.CrossRef O'Malley DP. T-cell large granular leukemia and related proliferations. Am J Clin Pathol. 2007;127(6):850–9.CrossRef
11.
go back to reference Zambello R, Teramo A, Gattazzo C, Semenzato G. Are T-LGL leukemia and NK-chronic Lymphoproliferative disorder really two distinct diseases? Transl Med @ UniSa. 2014;8:4–11. Zambello R, Teramo A, Gattazzo C, Semenzato G. Are T-LGL leukemia and NK-chronic Lymphoproliferative disorder really two distinct diseases? Transl Med @ UniSa. 2014;8:4–11.
12.
go back to reference Grant C, Wilson WH, Dunleavy K. Neutropenia associated with rituximab therapy. Curr Opin Hematol. 2011;18(1):49–54.CrossRef Grant C, Wilson WH, Dunleavy K. Neutropenia associated with rituximab therapy. Curr Opin Hematol. 2011;18(1):49–54.CrossRef
13.
go back to reference Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine. 2010;89(5):308–18.CrossRef Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine. 2010;89(5):308–18.CrossRef
14.
go back to reference Pontikoglou C, Kalpadakis C, Papadaki HA. Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia. Expert Rev Hematol. 2011;4(3):317–28.CrossRef Pontikoglou C, Kalpadakis C, Papadaki HA. Pathophysiologic mechanisms and management of neutropenia associated with large granular lymphocytic leukemia. Expert Rev Hematol. 2011;4(3):317–28.CrossRef
15.
go back to reference Gross CC, Ahmetspahic D, Ruck T, Schulte-Mecklenbeck A, Schwarte K, Jorgens S, et al. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis. Neurol(R) Neuroimmunology Neuroinflammation. 2016;3(6):e289.CrossRef Gross CC, Ahmetspahic D, Ruck T, Schulte-Mecklenbeck A, Schwarte K, Jorgens S, et al. Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis. Neurol(R) Neuroimmunology Neuroinflammation. 2016;3(6):e289.CrossRef
16.
go back to reference Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39.CrossRef Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39.CrossRef
17.
go back to reference Vakrakou AG, Tzanetakos D, Valsami S, Grigoriou E, Psarra K, Tzartos J, Anagnostouli M, Andreadou E, Evangelopoulos ME, Koutsis G, Chrysovitsanou C, Gialafos E, Dimitrakopoulos A, Stefanis L, Kilidireas C. A case of Alemtuzumab- induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes. BMC Neurology, 2018. Vakrakou AG, Tzanetakos D, Valsami S, Grigoriou E, Psarra K, Tzartos J, Anagnostouli M, Andreadou E, Evangelopoulos ME, Koutsis G, Chrysovitsanou C, Gialafos E, Dimitrakopoulos A, Stefanis L, Kilidireas C. A case of Alemtuzumab- induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes. BMC Neurology, 2018.
Metadata
Title
A case of Alemtuzumab-induced neutropenia in multiple sclerosis in association with the expansion of large granular lymphocytes
Authors
A. G. Vakrakou
D. Tzanetakos
S. Valsami
E. Grigoriou
K. Psarra
J. Tzartos
M. Anagnostouli
E. Andreadou
M. E. Evangelopoulos
G. Koutsis
C. Chrysovitsanou
E. Gialafos
A. Dimitrakopoulos
L. Stefanis
C. Kilidireas
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2018
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-018-1183-4

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