Cyclophosphamide therapy in pediatric
N. Makhani, MD
M.P. Gorman, MD
H.M. Branson, MD
L. Stazzone, NP
B.L. Banwell, MD
T. Chitnis, MD
Objective: To review our multicenter experience with cyclophosphamide in the treatment of chil-
dren with multiple sclerosis (MS).
Methods: Retrospective chart review of children with MS treated with cyclophosphamide. Demo-
graphic, clinical, treatment, and MRI parameters were collected.
Results: We identified 17 children with MS treated with cyclophosphamide. All but one had wors-
ening of Expanded Disability Status Scale scores or multiple relapses prior to treatment initiation.
Children were treated with one of three regimens: 1) induction therapy alone; 2) induction therapy
with pulse maintenance therapy; or 3) pulse maintenance therapy alone. Treatment resulted in a
reduction in relapse rate and stabilization of disability scores assessed 1 year after treatment
initiation in the majority of patients. Longer follow-up was available for most cases. Cyclophosph-
amide was well tolerated in most patients. However, side effects included vomiting, transient
alopecia, osteoporosis, and amenorrhea. One patient developed bladder carcinoma that was suc-
Conclusions: Cyclophosphamide is an option for the treatment of children with aggressive multi-
ple sclerosis refractory to first-line therapies. Recommendations regarding patient selection,
treatment administration, and monitoring are discussed. Neurology®2009;72:2076–2082
ARR ? annualized relapse rates; EDSS ? Expanded Disability Status Scale; IVIg ? IV immunoglobulin; MS ? multiple sclerosis;
PLEX ? plasmapheresis; RRMS ? relapsing remitting multiple sclerosis; SPMS ? secondary progressive multiple sclerosis.
Intravenous cyclophosphamide (Cytoxan™; BMS Oncology, Princeton, NJ) is an alkylating
agent that is used mainly as a second-line treatment in multiple sclerosis (MS). It is
generally administered as monthly maintenance therapy, in some cases preceded by an
induction course. Cyclophosphamide has been shown to be effective in relapse rate reduc-
tion1,2and in control of MRI lesion accrual1,3; however, effects in delaying disease progres-
sion have been variable.4-7Several studies have suggested that cyclophosphamide treatment
may be most beneficial in younger adult patients,7-9and in patients with early secondary
MS onset before the age of 18 years is estimated at 2.7%–10.5%11-13of all patients. Children
experience more frequent relapses than adults, suggesting a highly inflammatory disease.14
Several studies have demonstrated that on average, patients with pediatric-onset MS have a
longer disease duration from first attack prior to the onset of progressive disability, although
the age at which this outcome is achieved is younger than is seen in adult-onset MS.11,13,15A
Editorial, page 2064
Address correspondence and
reprint requests to Dr. Tanuja
Chitnis, Partners Pediatric
Multiple Sclerosis Center,
Massachusetts General Hospital,
ACC-708, 55 Fruit Street,
Boston, MA 02114
e-Pub ahead of print on May 13, 2009, at www.neurology.org.
From The Hospital for Sick Children (N.M., H.M.B., B.L.B.), University of Toronto, Canada; Partners Pediatric Multiple Sclerosis Center (M.P.G.,
T.C.), Massachusetts General Hospital for Children, Boston; Children’s Hospital (M.P.G.), Boston; and Partners Multiple Sclerosis Center (L.S.,
T.C.), Brigham and Women’s Hospital, Boston, MA.
Supported by the Pediatric Multiple Sclerosis Centers of Excellence Grant from the National Multiple Sclerosis Society, USA (T.C.), and by the
Multiple Sclerosis Scientific Research Foundation of Canada (B.L.B.). M.P.G. is supported by a National Multiple Sclerosis Society (Central New
England Chapter) Clinical Fellowship.
Disclosure: The authors report no disclosures.
Medications: Cyclophosphamide (Cytoxan™; BMS Oncology, Princeton, NJ).
Copyright © 2009 by AAN Enterprises, Inc.
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