Bone marrow

tranplantation
Nanis Sacharina

A week-observation in
Centro Trapianti di Midollo Osseo,
Ospedale Microcitemico,
Cagliari, 7-16 Dec 2005
Ospedale Microcitemico
History – team work
Start in 1993
1 BMT unit, outpatient clinic
7 doctors, 10 nurses (+ 2 nurses for clinic)
molecular laboratory:
3 doctors
1 biologist
2 technicians
Every day meeting
Meeting
Indication
Thalassemia (110 patients)
leukemia
solid tumor
SCID
aplastic anemia
Survival rate
Familial donor
43 patients (1-15 yo), 120 months follow-up
• Disease free survival rate: 95%
• 2 deaths
32 patients (16-34 yo), 120 months follow-up
• Disease free survival rate 88%
Non familial donor
17 patients
• Disease free survival rate : 65%
CTMO, Ospedale Microcitemico, Cagliari
Survival rate (Thalassemia)
36 class 1 and 2 thalassemic patients, 72 mo
follow-up
Survival rate 96%
Thalasemia free survival rate 85%
Class 1: 100%, class 2: 75%
35 class 3 patients, 12 years follow-up
thalasemia free survival rate 50%
Risk classes in thalassemic
patients at the time of BMT

Risk factors class I class II class III

Hepatomegaly <2 Ø2
Only one or a
Portal fibrosis No combination of Yes
two risk factors
Iron chelation regular out of three Irregular
Umbilical cord
Graft failure 21%
Long period of aplasia
Thalassemia: 7/33 failed
Sickle cell 1/ 11 failed
Protocol
HLA typing:
Class I: A, B, C
Class II: DQ, DR, DP
Parents/ patients agreement
Informed consent
Several work-up and laboratory test
List serologically-identifiable HLAs
Locus A Locus B Locus C Locus DR Locus DQ
1 5: 51, 52 w1 1: 103 1: 5, 6

2: 203, 210 7 W2 2: 15, 16

3 8 w3,: w9, w10 3: 17, 18 2

9: 23, 24, 2403 12: 44, 45 W4 4 3: 7, 8, 9

13
10: 25, 26, 34, 66 14: 64, 65 W5 5: 11, 13 4
11: 15: 62, 63, 75, 76, W6 6: 13, 14, 1403,
19: 29, 30, 31, 32, 77 W7 1404
33, 74 16: 38, 39 w8 7
28: 68, 69 17: 57, 58 8
36 18 9
43 21: 49, 50, 4005 10
80 22: 54, 55, 56
etc 51
52
53
Compatibility and incompatibility

Full compatibility = full-house/ zero mismatch:

the best!
Donor: A26 A32 B38 B55 DR1 DR4
Receiver: A26 A32 B38 B55 DR1 DR4
Poor compatibility
Donor: A26 A32 B38 B55 DR1 DR4
Receiver: A1 A32 B17 B35 DR9 DR7
Laboratory (donor and recipient)

Mixed lymphocyte culture

DNA extraction
4 ml of serum
fT3-fT4-TSH
Lymphocyte subset
tuberculine test
Ig-C3-C4
Liver and renal function test
VNTR
Laboratory
Anti toxoplasma-CMV Anti platelet antibody
antibody ferritine
anti EBV nasal and pharyngeal
anti herpes simplex culture
and zooster rectal/ preputium/
anti HCV-HCV RNA perineal swab-culture
markers HBV urine culture
anti HIV PT, PTT
VDRL Electrophoresis Hb,
protein
Work-up
ECG-cardiology consultation
echocardiography
Chest X-ray
bone age (> 2 yo)
spirometry (age 7)
Donor preparation
Erythropoetin
Iron
Folic acid
‘Blood predeposit’ prevent random
transfusion
BMT unit
kitchen

1
Nurse station

Doctor’ station
2

bagno

3
Mini lab
4
Patient’s room
cupboard

bathroom

Patient’s room
Parent’s room
BMT unit
Fausto with us
Patient’s room
Patient’s room
BMT Protocol (thalassemia)
Vena central catheter insertion under
general anesthesia (7 days before day -10),
day care
admission to the BMT unit on day -10
suppress the defected marrow and prevent
GvHD
hydration and alkalinitation start 12 hours
before administration of busulfan
Bone marrow suppression
Busulfan 4 days: 14 mg/kg
hydration 3 L/m2 until day -1
alkalinisation: NaHCO3
KCl
Furosemid
carbamazepine
Co-trimoxazole
CPA/ endoxan 4 days: 200 mg/kg
mesna
hydration
Other drugs
Colimicin
neomicin
nistatin
azyclovir
ondansetron
chlorpheniramin
GvHD prevention
Cyclosporin A
Methylprednisolone
ranitidine
Methotrexate if necessary
Monitoring
Every day
CBC
blood gas analysis, electrolyte (during
alkalinisation)
balance diuresis
Bone marrow harvesting &
retransfusion
Under general anesthesia
Operating room
20 ml/ kg recipient, nucleated cells 3.5-4 x
108/ kg
BM retransfusion as soon as possible
depends on ABO compatibility:
plasma removal: minor
red blood cell removal: major
After BMT
Grafted or not?
VNTR: before BMT and > +10 day
Usually take 12-20 ( to 30) days
Complication
Infection: special concern of IgG EBV and
CMV positive à reactivation?
Acute GvHD (familial donor 20%, non familial
60%)
Discharge criteria
Good condition overall
No infection, GvHD
Laboratory normal
Follow-up after discharge
First year: monthly
Afterwards: 2 monthly
Infection
Chronic GvHD
Chronic GvHD