Professional Documents
Culture Documents
Dr Josu de la Fuente
Imperial College Healthcare
St. Mary’s Hospital
London
Survival of Patients with β Thalassaemia
Hypertransfusion Ciclosporin
MTX
Busulfan
14 mg/kg Cyclophosphamide
200 mg/kg
Alemtuzumab Stem Cells
0.3 mg/kg 4 – 6 x 108/kg
Imperial College Healthcare
1994 - 2007
69.5%
13%
Total
No patient dropped < 90% donor haemopoiesis beyond D +90
Limitations of SCT
• Lack of donors • Length of Treatment:
– 2 months as an inpatient
– 4 months as outpatient
• Transplant Related Mortality
• Long Term Effects:
– Infertility
– Pubertal failure
– Chronic GvHD
– Organ toxicity
– Secondary malignancy
SCT for β
Thalassaemia Cy = 200 mg/kg
1985 - 2007
•Age ≥ 7 years
•Liver ≥5 cm
•Azathioprine and HU to
reduce haemopoiesis
•Fludarabine 100 mg/m2
•Busulfan 14 mg/kg
•Cyclophosphamide 160 mg/kg
•23 children
•AML
<7 years
≥7 years
•47 patients
•Bu 13 mg/kg and Cy
200 mg/kg
•CSA and MTX
Latest change of 0.48 32 0.18 to 0.66 19 0.27 to 0.2 (0.82)13 -0.24 to .166
HtSDS (0.87) 0.78 (0.87) 1.05 0.65
1991-1999 n = 50
47 surviving
patients:
• 5 recurrent sickle
cell disease
• 4 stable mixed
chimerism
• 38 full donor
haemopoiesis
OS: 93%
All patients DFS: 85%
EFS: 82%
OS: 88%
SCT because of DFS: 80%
morbidity
EFS: 76%
OS: 100%
SCT to return to
DFS: 93%
country of origin
EFS: 93%
Deaths 2 4 0
Rejections/nonengraftment 5 0 2
aGVHD grade 2 or above (%) 5 (19.2) 7 (41) 5 (11)
cGVHD (%) 4 5 2
3
months
12
• Assessed by the presence of Howell-Jolly bodies on
months blood films and (99mTc) splenic uptake.
• After BMT: Howell-Jolly bodies disappeared whereas
99mTc isotopic scan found normal isotope uptake.
Boys
Girls
Girls
Boys
CB Graft Characteristics
• Transplant-related complications:
– OS: 100%
– EFS at 2 years:
• Pesaro class I: 89%
• Pesaro class II: 62%
– No cases of life-threatening infection
– GvHD:
• Acute: 11%
• Chronic: 6%
Locatelli, Blood 2003
Locatelli, Blood 2003
Zhongshan University Experience
• 9 Chinese patients with β -thalassaemia major who underwent sibling CBT.
• Median age at transplant: 5.5 years (range 3.5-10)
• Pesaro risk:
– Class 2: 6/9
– Pesaro 3: 3/9
• HLA matching:
– HLA identical: 6/9
– 1 Ag mismatch: 1/9
– 3 Ag mismatch: 2/9
• Conditioning regimen:
– BU (~14-20 mg/kg) / CY (~160-200 mg/kg) / melphalan (90 mg/m2) / ATG
– escalating doses were adopted with successive patients, due to early findings of graft failure
• GVHD prophylaxis:
– CSA and methylprednisolone: 6/9
– CSA and MTX: 3/9
• Cell dose: 6.6 x 107 TNC/Kg (range 3.4-12.7). Two patients supplemented with
neonatal blood (to increase cell dose by 20-30%).
• Outcome:
– 4/7: primary graft failure with autologous reconstitution (1/4 following
myeloablative conditioning and 3/3 after RIC).
– Of the 3 patients with donor engraftment: 1 died of multiorgan failure and 2
remain alive and well, free of disease and transfusion-independent.
– 1/3 primary graft failure after RIC received a second unrelated CBT (TBI) and is
alive and well, free of disease.
A B C
Age (years) 4 15 13
•Pesaro class I: 4
•Pesaro class II: 11
•Pesaro class III: 17
BU14-TT10-CY120
La Nasa, Blood 2002
RIC for Sickle Cell Disease
n=2