1. Bone marrow Transplant in Paediatric Haematology
Rob Wynn
Consultant Paediatric Haematologist
Director Paediatric BMT Programme

2. Understanding BMT Two competing immune systems Recipient wins
Donor vs Recipient
Recipient wins
Rejection
Relapse
Transplant fails
Donor wins
Graft versus host disease
Remission of malignant disease
Transplant is a succes

3. Donor immunity recipient immunity

4. Supporting engraftment
Recipient ablation
Donor bone marrow
Myeloablative chemo-
radiotherapy
Time after BMT

6. 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

7. 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

8. 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,

9. Sources of HSC Sibling Other family members Haplo-identical
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

10. Sources of stem cells Bone marrrow Umbilical cord blood
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

11. 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

12. Complications of transplant (1)
Complications of High Dose chemotherapy
Acute
Mucositis
Liver – VOD – weight gain, jaundice, hepatomegaly
Chronic
Infertility
Growth
Second malignancy

13. 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

16. 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