ETHICS for LUNCH: Parental
Request for Experimental
Therapy for a Child
J.M. Lorenz, MD
February 16, 2006
THE CASE
Timmy is a 6 month old infant who was
well until ~ 3 mo of age when parents
noted loss of tone and movement in
his lower extremities. A diagnosis of
Spinal Muscular Atrophy-Type 1 (SMA)
was made by a pediatric neurologist.
Subsequently, the diagnosis was
genetically confirmed.
Spinal Muscular Atophy–Type I
(aka Werdnig-Hoffamann disease)
• Progressive neurodegenerative disorder
affecting anterior horn cells
• No known specific therapy
• All children with SMA become quadriplegic
• Mental status remains completely normal
• In the past, average life span was two
years; more recently with more aggressive
care at least some children with the
disease are now surviving to school age.
THE CASE
Condition at presentation to
MSCHONY:
• Severely hypotonia with little
movement of the upper extremities
and absent deep tendon reflexes
• Cranial nerves function intact
• Breathing is diaphragmatic, but
without respiratory distress
• Able to breast feed.
QUESTION
The bone marrow transplantation
specialists (Dr. K) requested an
ethics consultation regarding
whether it ethical to offer a stem
cell transplant, a highly
experimental therapy, to a baby
with SMA-type 1.
RELEVANT ISSUES ?
RELEVANT ETHICAL
PRINCIPLES
• Beneficence
• Best interest standard
• Parental autonomy
• Distributive Justice
Stem cell transplant for
SMA: BENEFIT ?
• Stem cell transplantation as a therapy for SMA is
based on the theory that pleuripotential cells can
replace the damaged anterior motor neurons
• There are no in vitro, animal, or human data
regarding stem cell transplantation for SMA
• Stem cell transplantation has been successful
and resulted in clinical benefit in several
neurologic diseases
• This demonstrates the possibility of stem cell
reaching the central nervous system, but the
defective cells in these diseases are not anterior
horn cells as in SMA
Stem cell transplant for
SMA: BENEFIT ?
• The closest analogous condition in adults is
amyotrophic lateral sclerosis (ALS)
• Results of stem cell transplants in animal
models of ALS have been mixed
• At a recent conference, investigators who had
performed stem cells transplants in human
adults with ALS were criticized for doing so
with insufficient preclinical research
• The scientists with expertise in SMA, whom the
parents have contacted, are evenly spilt as to
whether this procedure should be performed.
Stem cell transplant for SMA:
BENEFIT IN THIS CASE ?
• The benefit is “indefinable”
• The availability of cord blood with a perfect HLA
match in this case makes the likelihood of
engraftment high
• It is unknown whether the transplant will alter
the course of the disease; at best, however, Dr.
K believes that it may slow or halt the
progression of the disease, but not result in
recovery of lost function
• Were the transplant to be performed
– extensive pre and post neurological and
pulmonary function testing will be performed
– If and when the child expires, autopsy permission
will be sought to confirm CNS engraftment.
Stem cell transplant for
SMA: RISKS
• Timmy is eligible for the lowest risk IRB
approved immunosuppression protocol for
nonmalignant diseases
• Experience with this protocol has shown little
serious toxicity from the immunosuppression
drugs
• The perfect HLA match in this case
considerably reduces risk of graft versus host
disease: the risk of lethal graft versus host
disease is no greater than 10%.
The Family
• Timmy’s parents proactive, well informed, and
medically sophisticated
• Stored cord blood is available from a previous child,
who is a perfect HLA match with Timmy
• The have consulted neurologists, geneticists, stem
cell biologists, the SMA Foundation, numerous
internet sites, and parents of children with SMA
•
• They have had extensive counseling regarding
prognosis and care required for children with SMA,
as well as the risk and experimental nature of stem
cell transplantation for SMA
•
• After careful consideration, the parents are united in
their desire for the stem cell transplant
SUMMARY: RELEVANT ISSUES
1. The child’s prognosis without treatment is
very guarded, but survival for some period
of years is possible.
2. Judgment of quality of that survival is very
subjective and, therefore, the purview of
the parents
3. The basis for performing stem cell
transplantation is purely theoretical,
without any in vitro, animal or human data.
4. The procedure carries a risk of death that
may be as high as 10% with the lowest risk
immunosupression protocol
SUMMARY: RELEVANT ISSUES
5. Engraftment is likely, but the likelihood of
any clinical benefit to the child is
unquantifiable.
6. The basis of the decision should first and
foremost be Timmy’s best interest.
7. The family seems to be well informed and
have Timmy’s best interest of at heart.
8. The results of this stem cell transplant may
provide important information that could
benefit patients in the future.
COMMITTEE OPINION
• Stem cell transplantation, with the informed
parental consent, is an ethically acceptable
option in this case
• Consideration of Timmy’s best interest and
parental understanding of the disease, its
prognosis, the care the child will require, the
real risk of death, and the unknown benefits of
and the experimental nature of stem cell
transplantation are absolutely essential to this
decision
• Given the experimental nature of the
procedure, care should be taken to learn as
much as possible from this experience if it is
undertaken.
RESOLUTION
At a subsequent meeting with the
parents very shortly after the
initial consultation, the Director
of the Bone Marrow Transplant
Center related the issues and
concerns that had been raised
by the Ethics Committee. At that
time the parent decided against
stem cell transplantation.