Bone Marrow Tranplantation

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    Bone marrowtranplantation

    Nanis Sacharina

    A week-observation in

    Centro Trapianti di Midollo Osseo,Ospedale Microcitemico,

    Cagliari, 7-16 Dec 2005

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    Ospedale Microcitemico

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    History team workStart 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

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    Meeting

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    IndicationThalassemia (110 patients)

    leukemia

    solid tumor

    SCID

    aplastic anemia

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    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 donor17 patients

    Disease free survival rate : 65%

    CTMO, Ospedale Microcitemico, Cagliari

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    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-upthalasemia free survival rate 50%

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    Risk classes in thalassemic

    patients at the time of BMT

    Risk factors class I class II class IIIHepatomegaly < 2

    Only one or a

    combination of

    two risk factors

    out of three

    2

    Portal fibrosis No Yes

    Iron chelation regular Irregular

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    Umbilical cordGraft failure 21%

    Long period of aplasia

    Thalassemia: 7/33 failed

    Sickle cell 1/ 11 failed

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    ProtocolHLA typing:

    Class I: A, B, C

    Class II: DQ, DR, DP

    Parents/ patients agreement

    Informed consent

    Several work-up and laboratory test

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    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

    13

    W4 4 3: 7, 8, 9

    10: 25, 26, 34, 66

    11:

    19: 29, 30, 31, 32,

    33, 74

    28: 68, 69

    36

    43

    80

    14: 64, 65

    15: 62, 63, 75, 76,

    77

    16: 38, 39

    17: 57, 58

    18

    21: 49, 50, 4005

    22: 54, 55, 56

    etc

    W5

    W6

    W7

    w8

    5: 11, 13

    6: 13, 14, 1403,

    1404

    7

    8

    9

    10

    51

    52

    53

    4

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    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

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    Laboratory (donor and recipient)

    Mixed lymphocyte culture

    DNA extraction

    4 ml of serumfT3-fT4-TSH

    Lymphocyte subset

    tuberculine test

    Ig-C3-C4Liver and renal function test

    VNTR

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    LaboratoryAnti toxoplasma-CMV

    antibody

    anti EBV

    anti herpes simplex

    and zooster

    anti HCV-HCV RNA

    markers HBV

    anti HIV

    VDRL

    Anti platelet antibody

    ferritine

    nasal and pharyngeal

    culture

    rectal/ preputium/

    perineal swab-culture

    urine culture

    PT, PTTElectrophoresis Hb,

    protein

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    Work-upECG-cardiology consultation

    echocardiography

    Chest X-ray

    bone age (> 2 yo)

    spirometry (age 7)

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    Donor preparationErythropoetin

    Iron

    Folic acid

    Blood predeposit prevent random

    transfusion

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    BMT unit

    2

    1

    3

    4

    kitchen

    Nurse station

    Doctor station

    bagno

    Mini lab

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    Patients room

    bathroom

    Parents room Patients room

    cupboard

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    Fausto with us

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    Patients room

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    Patients room

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    BMT Protocol (thalassemia)Vena central catheter insertion undergeneral anesthesia (7 days before day -10),

    day careadmission to the BMT unit on day -10

    suppress the defected marrow and preventGvHD

    hydration and alkalinitation start 12 hoursbefore administration of busulfan

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    Bone marrow suppressionBusulfan 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/kgmesna

    hydration

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    Other drugsColimicin

    neomicin

    nistatin

    azyclovir

    ondansetron

    chlorpheniramin

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    GvHD preventionCyclosporin A

    Methylprednisolone

    ranitidine

    Methotrexate if necessary

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    MonitoringEvery day

    CBC

    blood gas analysis, electrolyte (duringalkalinisation)

    balance diuresis

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    Bone marrow harvesting &

    retransfusionUnder general anesthesia

    Operating room

    20 ml/ kg recipient, nucleated cells 3.5-4 x108/ kg

    BM retransfusion as soon as possible

    depends on ABO compatibility:plasma removal: minor

    red blood cell removal: major

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    After BMTGrafted 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 reactivation?

    Acute GvHD (familial donor 20%, non familial

    60%)

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    Discharge criteriaGood condition overall

    No infection, GvHD

    Laboratory normal

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    Follow-up after dischargeFirst year: monthly

    Afterwards: 2 monthly

    Infection

    Chronic GvHD

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    Chronic GvHD