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Leukemia Research 34 (2010) e154–e156

Contents lists available at ScienceDirect

Leukemia Research

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / l e u k r e s

Letter to the Editor

Guillain–Barré syndrome after use of alemtuzumab (Campath)in a patient with T-cell prolymphocytic leukemia: A case reportand review of the literature

1. Introduction

Alemtuzumab (marketed as Campath, MabCampath or

Campath-1H) is a recombinant DNA-derived humanized mono-

clonal antibody that is directed against the 21–28kDa cell surface

glycoprotein, CD52. Binding of alemtuzumab to CD52 initiates

complement activation via the classical pathway [1]. The mem-

brane attack complex that is formed in this way leads to lysis of

lymphocytes. Alemtuzumab is used in the treatment of chronic

lymphocytic leukemia (CLL) and T-cell lymphoma.

A major complication with alemtuzumab therapy is the

increased risk for opportunistic infections. In particular, reactiva-

tion of cytomegalovirus has been frequently reported. Although

alemtuzumab is a potent immunosuppressant, several groups have

described the paradoxical occurrence of autoimmune disease after

its use, including thyroid disorders and cytopenias [2–4]. Although

a direct causational association has not been established, patients

who received alemtuzumab in conditioning regimen for stem cell

transplantation have been reported to develop static peripheral

neuropathy of unknown pathogenesis [1]. GBS is an autoimmune

disorder in which the peripheral nervous system becomes the tar-

get of host-mediatedimmunedestruction.We describea report of a73-year-old man with T-cell prolymphocytic leukemia, who devel-

oped GBS following treatment with alemtuzumab. No antecedent

infective etiology was identified. Although there are numerous

reports of autoimmune disease after treatment with alemtuzumab

and GBS after immunosuppressive treatment, we could find only

one additional report of GBS after the use of alemtuzumab.We will

also discuss the occurrence of autoimmune disease after immuno-

suppressive treatment as a general phenomenon, and in particular

with alemtuzumab, and the possible mechanisms for this autore-

active T-cell dysregulation.

2. Case report

A 73-year-old male was found to have elevated white blood

cell count of 20.6 with differential showing lymphocytosis with

absolute lymphocyte count of 16.5. Other values were Hgb of 12.4

and platelet count of 244,000. Flow cytometry, T-cell receptor

gene rearrangement studies, and bone marrow biopsy established

the diagnosis of T-cell prolymphocytic leukemia (T-PLL). He was

treated with a course of intravenous alemtuzumab (1 dose of 3 mg,

2 doses of 10 mg and 12 doses of 30 mg in 34 days). He responded

well to the treatment and complete remission was achieved. He

came to the ED with 2-day history of falls and one week history

of numbness and tingling, 62 days after the completion of treat-

ment. The patient had also experienced some mild diarrhea after

the chemotherapy which ultimately resolved 5–7 days after his

prophylactic sulfamethoxazole/trimethoprim was stopped. At the

time of admission strength in all the extremities was MRC scale

of 4/5. Cranial nerve examination was normal, no facial asymme-

try was noted. He did complain of some tingling sensation in his

feet and hands. He also described his legs as rubbery. The reflexes

at the time of admission were 2+ in upper extremities and 1+ in

lower extremities. MRI of the brain did not reveal any abnormali-

ties. Based on this clinical picture, a provisional clinical diagnosis

for GBS was made and the patient was admitted to the hospital. At

the time of admissionhis WBC countwas 4.9, Hgb11.6, hematocrit

33.8 and platelets were 199,000. In the next 48 h, he rapidly lostadditional strengthfirst in lower extremities, progressing rapidly to

involve upperextremities by the 4th day of admission. Electromyo-

graphy and nerve conduction studies showed a generalized motor

and sensory polyneuropathy withmixed axonal and demyelinating

features consistent withdiagnosis of GBS.CSF analysisshowedclear

appearance with no color. Differential cell count of CSF showed


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Letter to the Editor / Leukemia Research 34 (2010) e154–e156 e155

cytes, B lymphocytes [5] and monocytes [6]. Alemtuzumab has an

established role in the treatment of CLL and has become the treat-

ment of choice for T-PLL [7]. Alemtuzumab induces rapid profound

lymphopenia that canlast up to 18 months [8]. Alemtuzumab have

also been used as a conditioningagent for non-myeloablative bone

marrow transplantation and in the treatment of acute graft ver-

sus host disease [9,10]. The lymphopenia caused by alemtuzumab

is associated with profound immunosuppression. Opportunistic

infections with agents such as CMV frequently occur and patients

must be monitored for reactivation [11]. In addition to decreasing

effector immune cells, it also results in dysregulation of CD4CD25

regulatory T cells. These cells normally inhibit autoimmune acti-

vated cells and this indiscriminant dysregulation may predispose

to the development of autoimmunity. In addition, CD52 anti-

gens are also expressed on monocyte-derived dendritic cells and

thus antigen presentation in the host is affected following alem-

tuzumab treatment [12,13] Immature peripheral dendritic cells

present antigen to T cells in a tolerogenic manner by silencing

activated T cells, activating and causing expansion of regulatory T

cells, and causing the differentiation of naive CD4 cells into reg-

ulatory T cells [14–16]. The effect of alemtuzumab in depleting

these dendritic cells may also predispose to the development of

autoimmunity.

Furthermore, alemtuzumab has been shown to deplete natu-ral killer cells; studies suggest these cells may play a role in both

exacerbating and protecting against autoimmune mechanisms

[12]. After the administration of alemtuzumab, B-cell recovery

tends to precede T-cell recovery, and the number of B cells may

exceed baseline values in somepatients[17]. Autoimmunediseases

observed after the administration of alemtuzumab are predomi-

nantly antibody-mediated, and they respond to B-cell depletion

[18]. Autoreactive B cells can function without T-cell help [19].

Thus, the emergence of autoreactive B cells during the reconstitu-

tion of lymphocytes may also cause autoimmunity after treatment

with alemtuzumab.

In summary,treatment withalemtuzumabinducesa widerange

of perturbations in the various components of the adaptive and

innate immune system, from which recovery and reconstitutionoccur within different time frames and to different extents. These

immune dysregulations may set the stage for the development of

autoimmunity within the concurrent profound immunosuppres-

sive environment created by this agent.

Similar immune dysregulations hasalso beendescribed afterthe

use anothermonoclonalantibody rituximab. Rituximabis antiCD20

monoclonal antibody used in the treatment of many hematologi-

cal malignancies. Various case reports have mentioned about the

correlation of rituximab use leading to GBS [20,21]. The mecha-

nism of action in those cases is not clear but the hypothesis is

that CD20 down regulation during B-cell maturation and loss of

feedback mechanism may be the cause.

Guillain–Barré syndrome (GBS) is a disorder in which the

body’s immune system attacks part of the peripheral nervoussystem by destroying the myelin sheath that surrounds the

axons of many peripheral nerves, or even the axons them-

selves. It is believed to be caused by autoimmune mechanisms

that are predominantly T-cell mediated. It is a rare but rec-

ognized event after autologous and allogeneic bone marrow

transplantation, intensive conditioning regimens, and solid organ

transplantation. GBS is also well documented in conditions where

immune dysfunction is a feature, notably Hodgkin and non-

Hodgkin lymphoma, HIV infection, and numerous autoimmune

disorders such as chronic active hepatitis, hypothyroidism, sar-

coidosis, Wegener’s granulomatosis, and ulcerative colitis. It is

postulated that in these situations GBS may arise as a result of

viral infection/reactivation or as a result of the iatrogenic immune

dysregulation.

Ourpatient hadsymptoms of mild diarrhea precedingthe onset

of GBS. It is possible that an underlying infection might have

elicited an immune response leading to GBS, although investi-

gations failed to detect viral or bacterial infection. Even T-cell

lymphoma in theory can lead to GBS but in our patient his last

bone marrow biopsy showed that he was in remission at that time.

Castelli et al. previously described a similar case of GBS occur-

ring in a patient with CLL who was treated with alemtuzumab

[22]. These two cases collectively suggest that the immunosup-

pressive state induced by alemtuzumab may predispose patients

to GBS. Molecular mimicry is another theory in which the anti-

bodies produced by body’s immune system to alemtuzumab cross

react to a host epitope leading to GBS. We postulate that alem-

tuzumab like other immunosuppressive agents may predispose

patients to develop GBS putatively via an autoimmune mechanism

resulting from indiscriminate dysregulation of regulatory T cells or

via molecular mimicry. Clinicians should be vigilant in monitoring

for the development of GBS in patients treated with alemtuzumab

and similar agents.

Conflict of interest

None.

Acknowledgments

Contributions: K.K.S.A. provided the conception and design of

the case report, along with acquisition of data analysis and inter-

pretation of data. S.M.R. helped in finding articles and references

forthe case report. J.S. helpedin understandingthe pharmacogenic

mechanism of action. S.T. provided the understanding of the basic

cause and effect relation of the drug and disease. T.L. provided

active input and feedback for the case report, who diagnosed and

treated the leukemia helped in the understanding of the initial

presentation of the patient and approved the final version. J.J.D.

helped in drafting the article and revised it critically for important

intellectual content.

References

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Kamal K.S. Abbi ∗

Syed M. Rizvi

Department of Internal Medicine Residency Program,

Penn State Milton S Hershey Medical Center,

500 University Drive, Hershey, PA 17033-0850, USA

Jeffrey Sivik

Department of Pharmacy,


Hershey, PA, USA

Subramanian Thyagarajan

Department of Neurology,


Hershey, PA, USA

Thomas Loughran

Joseph J. Drabick

Division of Hematology and Oncology,


Hershey, PA, USA

∗ Corresponding author. Tel.: +1 717 531 8521;

fax: +1 717 531 2034.

E-mail address: [email protected](K.K.S. Abbi)

20 October 2009

Available online 2 April 2010
mailto:[email protected]:[email protected]

abbi - guillain-barré syndrome after use of alemtuzumab (campath) in a patient with htlv-i with...

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