Epidemiologic Notes and Reports Aseptic Meningitis Among
Kidney Transplant Recipients Receiving a Newly Marketed Murine
Monoclonal Antibody Preparation
During July 1986, four patients being treated for kidney
allograft
rejection in two hospitals developed headache, fever, and
photophobia
(three patients) or fever alone (one patient) during administration
of
a recently marketed murine monoclonal antibody preparation,
Orthoclone
OKT3* (Ortho Pharmaceutical Corporation, Raritan, New Jersey). All
patients had onset of symptoms within 72 hours of beginning their
course of treatment with the product. OKT3 had been administered
daily as 5 mg OKT3 mixed with 50 ml normal saline and infused
intravenously over a 1-hour period. Lumbar puncture results on all
four patients suggested aseptic meningitis; they revealed
cerebrospinal fluid (CSF) pleocytosis, elevated CSF protein, and
normal CSF glucose. Initial CSF white blood cell counts ranged
from
18 to 445/mm((3)), with 40%-89% polymorphonuclear neutrophils. All
bacterial cultures of CSF and blood were sterile. Viral cultures
of
throat and stool were done in two patients and CSF in one patient;
all
have remained negative. Symptoms in all four patients resolved
within
5 days with no evidence of neurologic sequelae. Two of the
patients
received neither antibiotic nor antiviral therapy.
Four other patients who were treated for kidney allograft
rejection during July 1986 at the same hospitals but did not
receive
OKT3 had no signs or symptoms suggesting possible aseptic
meningitis.
All eight patients received other drug and therapeutic
interventions
commonly given to treat kidney allograft rejection.
Investigations of the reactions are currently under way by
hospital, state, Food and Drug Administration (FDA), and company
officials.
Reported by R Massanari, MD, M Martin, MD, University of Iowa
Hospitals and Clinics, J Smith, MD, D Nghiem, MD, RJ Corry, MD, M
Flanigan, MD, C Emmons, MD, University of Iowa Hospitals and
Clinics
and Veterans Administration Hospital, Iowa City, LA Wintermeyer,
MD,
State Epidemiologist, Iowa State Dept of Public Health; Div of
Blood
and Blood Products, Div of Epidemiology and Surveillance, Center
for
Drugs and Biologics, Food and Drug Administration; Hospital
Infections
Program, Div of Host Factors, Center for Infectious Diseases, CDC.
Editorial Note
Editorial Note: OKT3 has been reported effective in the treatment
of
acute kidney allograft rejection (1). Commonly reported adverse
reactions have included fever, chills, dyspnea, chest pain and
tightness, wheezing, nausea and vomiting, and tremor (1). In one
study, fever was reported in up to 73% of recipients. Reactions
were
noted 45-60 minutes after the first injection; second injections
were
associated with fewer reactions, and symptoms were uncommon in
subsequent injections (1). The incidence of aseptic meningitis
during
treatment with OKT3 is not known. Sixteen (2%) of 977 patients who
received OKT3 during premarket trials had a lumbar puncture.
Complete
information was available for only seven of the 16 patients. In
six
of the seven patients, CSF cell count, CSF protein, and CSF glucose
were consistent with aseptic meningitis; all bacterial, fungal, and
viral cultures were negative. The extent and nature of meningeal
pathology is unknown. Micrologic evaluation is incomplete for all
patients but suggests an immunologically mediated reaction as one
possible etiology. No clinical sequelae directly attributable to
the
reactions have been identified.
To assess the occurrence of aseptic meningitis and to establish
incidence rates in patients receiving OKT3, the FDA and Ortho
Pharmaceuticals have instituted a postmarket clinical evaluation of
the product. The company has provided additional information about
this evaluation to potential users of their product. Other
physicians
interested in this information should contact Ortho
Pharmaceuticals,
telephone (800) 433-1015; in New Jersey, (201) 218-6410.
Reference
Ortho Multicenter Transplant Study Group. A randomized
clinical
trial of OKT3 monoclonal antibody for acute rejection of
cadaveric
renal transplants. N Engl J Med 1985;313:337-42.
*Use of trade names is for identification only and does not
constitute
endorsement by the Public Health Service, U.S. Department of Health
and Human Services.
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