Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab

Saarela, Mika; Senthil, Keerthi; Jones, Joanne L.; Tienari, Pentti J.; Soilu‐Hänninen, Merja; Airas, Laura; Coles, Alasdair; Saarinen, Jukka T.

doi:10.1212/wnl.0000000000005420

Cited by 34 publications

(24 citation statements)

References 6 publications

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“…41 Haemophagocytic lymphohistiocytosis was reported in two patients with MS treated with alemtuzumab. 42 Other rare adverse effects are haemolytic anaemia 43 and alopecia. 44…”

Section: Alemtuzumabmentioning

confidence: 99%

Pulsed immune reconstitution therapy in multiple sclerosis

Sørensen

Sellebjerg

2019

Ther Adv Neurol Disord

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Whereas drugs used for maintenance/escalation therapy do not maintain their beneficial effect after cessation of therapy, some new highly effective therapies can show prolonged treatment effects after a short treatment course. Such therapies have been named pulsed immune reconstitution therapies or pulsed immunosuppressive therapies, and typical representatives are alemtuzumab and cladribine. Autologous haematopoietic stem cell transplantation could be considered as the strongest immune reconstitution therapy. Both alemtuzumab and cladribine induce depletion of lymphocytes, and a common mechanism of action is preferential depletion of class-switched and unswitched memory B-cells. Whereas CD-19+ B-lymphocytes repopulate within 6 months, CD4+ T-cells repopulate at a slower rate, taking 1–2 years to reach the lower level of normal. In general, the depletion of lymphocytes is more profound and the repletion of T-cells is slower after alemtuzumab than after cladribine treatment. Both drugs have a strong effect on relapses and magnetic resonance imaging (MRI) activity, and reduce disability worsening. The therapeutic effect is maintained beyond the period of active treatment in a large proportion of patients, which is best documented for alemtuzumab. Adverse effects include reactivation of latent infections such as tuberculosis and risk of herpes zoster. The main disadvantage in alemtuzumab-treated patients is the risk of secondary immune-mediated disorders. Pulsed immune reconstitution therapy is an option as initial therapy in relapsing-remitting multiple sclerosis patients with high disease activity and in patients on treatment with another disease-modifying therapy with significant relapse and/or MRI activity.

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“…41 Haemophagocytic lymphohistiocytosis was reported in two patients with MS treated with alemtuzumab. 42 Other rare adverse effects are haemolytic anaemia 43 and alopecia. 44…”

Section: Alemtuzumabmentioning

confidence: 99%

Pulsed immune reconstitution therapy in multiple sclerosis

Sørensen

Sellebjerg

2019

Ther Adv Neurol Disord

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“…In addition to this restriction, EMA’s safety committee (PRAC) has recommended an update of the product information in relation to cases of 5 (a) immune-mediated conditions, including autoimmune hepatitis and hemophagocytic lymphohistiocytosis; 6 (b) cardiovascular problems occurring within 1–3 days of receiving the medicine, including bleeding in the lungs, heart attack, stroke, and cervicocephalic arterial dissection; 7 and (c) severe neutropenia. 8,9…”

mentioning

confidence: 99%

Emerging safety issues in alemtuzumab-treated MS patients

Killestein

Oosten

2019

Mult Scler

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“…In the monthly Al monitoring program (blood tests), the determination of C-reactive protein (CRP) in the differential diagnosis may be helpful. In the presence of anemia, thrombocytopenia, pancytopenia and elevated CRP, a rare secondary hemophagocytic lymphohistiocytosis may be the cause that has been previously reported in two cases 32. This hyperinflammatory syndrome has occurred among others in autoimmune disease and this syndrome is characterized mainly by fever, pancytopenia, hyperferritinemia, pathological liver counts, raised soluble IL-2 receptor (CD 25), lymphadenopathy, and hemophagocytosis.…”

Section: Quick Recognition Of Unexpected Adverse Effects As Preventiomentioning

confidence: 89%

<p>Vitamin D supplementation for the prevention or depletion of side effects of therapy with alemtuzumab in multiple sclerosis</p>

Goischke¹

2019

TCRM

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Purpose of review: Not only the multiple sclerosis specialist but also the general neurologist and primary care practitioner are increasingly aware of possible adverse events (AEs) by treatment with alemtuzumab (over 47% risk of secondary autoimmune-mediated diseases). Vitamin D supplementation's effect (VDS) to reduce these autoimmune AEs is poorly performed in routine practice. This article seeks to justify why this simple, inexpensive, patient-friendly therapy should be seriously discussed. Recent findings: Patients who have developed autoimmunity also show a high basal level of IL-21, a cytokine which increases the growth of auto-reactive T-cells. For side effects such as thyroid dysfunction, autoimmune thrombocytopenia, autoimmune hemolytic anemia, autoimmune hepatitis, diabetes mellitus type 1, and alopecia areata/alopecia totalis, VDS may have an impact on the immunological mechanism, in particular lowering levels of IL-17 and IL-21. Summary: The potential role of vitamin D in influencing autoimmune diseases is evident. If a life-threatening side-effect can be prevented by high-dose VDS, it is ethical to initiate this add-on therapy despite contradictory results in studies on the effectiveness of VDS.

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Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab

Cited by 34 publications

References 6 publications

Pulsed immune reconstitution therapy in multiple sclerosis

Pulsed immune reconstitution therapy in multiple sclerosis

Emerging safety issues in alemtuzumab-treated MS patients

<p>Vitamin D supplementation for the prevention or depletion of side effects of therapy with alemtuzumab in multiple sclerosis</p>

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