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

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

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 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

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

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