Bone Marrow Transplantation in

Hurler syndrome
 Transplanted tissue
• Bone Marrow
Immature cells - stem cells
– White blood cells
– Red blood cells
– Platelets
• Peripheral blood stem cells
• Umbilical cord stem cells
 Tissue typing or matching
• Human leukocyte-associated antigens
(HLA)
• 25% chance of sibling match
• 30-40% chance HLA matched sib or parent
• Unrelated donors - 6 HLA and minor
antigens
 Bone Marrow Harvest
• Under anaesthesia
• Large needle into pelvis > sternum
• Blood and bone removed from sample
• Cryopreservation
• Donor side effects
– Local tenderness
– few days to 3-4 wks full recovery
 Peripheral Stem Cell Harvest
• Stem cells stimulated by Granulocyte
colony stimulating factor, G-CSF
• Blood removed via large vein
• Machine separates the stem cells
• Blood minus stem cells is returned via a
second canula
• Cryopreservation
 Cord Blood Collection
• Usually compatability known from prenatal
testing
• Blood collected from cord after cord cut.
• Stem cells separated in laboratory
• Cryopreservation
• (3/16 chance sib matching & unaffected;
1/16 matching and not affected or carrier)
Daria and her donor, Caleb
 The transplant
• Conditioning: patient’s own marrow
obliterated with chemotherapy
• Marrow or Stem cell Infusion: donor cells
infused via vein
• Engraftment - donor cells enter marrow and
start dividing ; 10-21 days
• Close medical supervision: 3 months
• Long term follow-up
Jack after insertion of portocath
Infusion of Marrow
 Complications of BMT

• Death
• Side effects of chemotherapeutic drugs
(Nausea, vomiting, fatigue, loss of appetite,
mouth ulcers, hair loss and skin reaction)
• Infections (viral, bacterial and fungal)
• Bleeding
Jack during Conditioning
 Complications of BMT
• Graft rejection
• Acute graft versus host disease, GVHD
(Skin rash; liver disease; gastrointestinal
disturbance; fever; oedema)
• Chronic GVHD: (skin, liver, eyes, mouth,
lungs, gastrointestinal system, nervous
system
Hair like my Dad
 Complications of BMT
• Veno-occlusive disease: blocking veins
draining liver
• Lung complications: infection, GVHD,
drugs, fluid
• Mucositis: ulceration mouth and gut
• Transfusions: red cells and platelets
(donor’s blood group).
Jack’s Isolation Room
 Complications of BMT
• Seizures / convulsions: haemorrhage, clot,
high blood pressure, infection, drugs
• Haemorrhagic cystitis: drugs or infection
• Hypertension: drugs
• Dental problems: infection, loss of enamel
Jack and his support team
 Late Complications of BMT
• Endocrine of hormone dysfunction -
growth, puberty, energy
• Infertility
• Lung complications: fibrosis
• Eye disease: cataract & dry eyes
• Kidney dysfunction
• Secondary malignancy
 Benefits of BMT for MPS 1H

• Maintenance of IQ
• Correction of hydrocephalus
• Improved hearing
• Normalised heart function
• Normalisation size of liver and spleen
• Survival
Jaime post BMT
 Persisting problems after BMT
for MPS 1H

• Skeletal changes
• Only partial correction corneal clouding
• Progression of retinal disease
• Heart valve changes
• Carpal tunnel syndrome
Jaime 11yrs post BMT
 BMT - Mechanisms
• Bone marrow cells produce the microglial
cells of the CNS
• Enzyme transfer between cells (spleen,
liver, lung, skin )
• Release of enzyme into plasma - then taken
up by host cell (won’t cross BBB)
• Concentration gradient storage product
 Determinants of Survival &
GVHD

• Matched sibling>matched related> matched

unrelated donor
• Regime of irradiation and chemotherapy
used
 Determinants of
Neuropsychological Outcome

• Age < 24 months

• IQ > 70
• Donor not a carrier > donor a carrier
• ? Severity of GVHD
 Psychosocial Aspects
• Limited time to decide whether or not to
have BMT
• Decision period while still coming to terms
with diagnosis
• High risk of losing child in their best years
• Disruption to family
• Outcome data lags changes in regimes
Daria pre BMT
 The Future

• BMT + ERT
• Continually improving regimes
Jaime 11 yrs post BMT
 Animal studies - BMT
MPS-IH (Hurler)
• Dog, cat and mouse
• enzyme activity CSF 7-15% donor
• Histol normal liver, kidney, brain glial cells,
no peripheral cell vacuolation
• variable decrease neuronal vacuolation
• marked vacuolation chondrocytes