Bone marrow Transplant in Paediatric Haematology

Rob Wynn

Consultant Paediatric Haematologist

Director Paediatric BMT Programme

Understanding BMT

• Two competing immune systems– Donor vs Recipient

• Recipient wins– Rejection– Relapse– Transplant fails

• Donor wins– Graft versus host disease– Remission of malignant disease– Transplant is a succes

Donor immunity recipient immunity

Supporting engraftment

• Recipient ablation

Donor bone marrow

Myeloablative chemo-radiotherapy

Time after BMT

Indications for HSCT

• Malignant diseases– Chronic leukaemias– Acute leukaemias – Myelodysplasia– Myeloma– Lymphoma

• Mode of Action of SCT in Malignant Disease– Graft versus Leukaemia– Intensity of Conditioning Therapy

Non malignant indications for BMT

• Haematological Indications– Disorders of HSC number – aplastic

anaemia, Fanconi anaemia– Red cell disorders – thalassaemia, sickle cell

anaemia, Diamond Blackfan Anaemia– White cell disorders – congenital

neutropenia, Schwachman Diamond– Lymphocyte disorders – immunodeficiency

(SCID), Haemophagocytic syndromes– Platelet disorders – Glanzmann’s

Non malignant indications for BMT

• Non haematological indications for HSCT

– Enzyme deficiency• Mucopolysaccharide disorders (MPS)• Adrenoleucodystrophy

– Disorders of Osteoclast function• Malignant Infantile Osteopetrosis (MIOP)

– Others (experimental)• Osteogenesis imperfecta (delivering MSC)

– Autoimmune disorders (delivering IS, resetting IS)• Systemic sclerosis,

Sources of HSC• Sibling

– 1:4 chance of matching where same parents• Other family members

– Only where consanguinity• Haplo-identical

– Parent, when desperate and need it quickly• Matched Unrelated Donor

– From donor registry– Largely caucasian donors– Unrelated UCB donor pools reflect ethnic mix of population better

• Autologous– Use and freeze patients own cells– +/- purging

Sources of stem cells

• Bone marrrow– Perhaps 1% of marrow MNC are CD34+

• Umbilical cord blood – Perhaps 1% of CB MNC are CD34+

• Mobilised peripheral blood– Can mobilise vast quantities of CD34+ cells– G-CSF to recipient– Leukapheresis of MNC fraction

Outcomes

• This is a risk balance question• Risk of disease

– Natural history etc• Risk of Transplant

– How well is the patient?– How well matched is the donor?

• Consent will include risk of death or serious morbidity balance against risk of no transplant

• Process and consent in transplant is more surgical than medical in type

Complications of transplant (1)

• Complications of High Dose chemotherapy– Acute

• Mucositis• Liver – VOD – weight gain, jaundice,

hepatomegaly

– Chronic• Infertility• Growth • Second malignancy

Complications of Transplant (2)

• Infection– Early – Neutropenic

• Bacterial – prophylaxis and treatment• Fungal – prophylaxis and treatment

– Late • Viral• Usually fatal infection is preceded by period of

asymptomatic viraemia• Screening – PCR – of blood urine stool weekly so as to

intervene with antivirals in this window period• Adenovirus, CMV, EBV

Complications of Transplant (3)

• Graft versus Host Disease• With HLA mismatch• Donor T cells against recipient tissue antigens

– Acute• SKIN, GUT, LIVER• Grade 0 - IV

– Chronic• ALL ORGANS (except brain)

• Will include Graft Versus Tumour• Prophylaxis with match and ciclosporin• Treat with steroids and other immune suppression