Cyclophosphamide/Fludarabine/TBI Reduced Intensity Conditioning for HLA-Haploidentical Related Transplant

Department of Clinical Haematology
Oxford BMT Programme
Cyclophosphamide/Fludarabine/TBI
Reduced Intensity Conditioning for HLA-Haploidentical Related Transplant
INDICATIONS
Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Myelodysplastic syndrome
Myeloma
Hodgkin’s disease
Non-Hodgkin’s lymphoma
Chronic lymphatic leukaemia
Graft failure of previous transplant
PRE-ASSESSMENT
•
•
•
•
•
•
•
•
•
•
Ensure pre-transplant investigations are carried out as per ‘work-up’ investigations form (B3.10b).
Ensure patient has triple lumen Hickman line in-situ and working (unless a working double lumen
line already in situ).
Ensure the results of pre-transplant investigations are checked by a Haematology SpR and recorded
in the patient’s records.
Ensure patient’s consent has been obtained.
Haematology SpR to complete electronic BMT front sheet and email to secretary to distribute and
file in patient records.
Prescribe chemotherapy and supportive treatment 10 days before admission
Send NHSBT Request form 2J to NHSBT for processing of bone marrow/stem cells at least 7
working days before the planned collection date and ensure a copy is placed in the medical notes.
Ensure donor clearance is obtained, reviewed and documented in recipient’s notes prior to
admission
Ensure that patient receives irradiated blood products from the start of conditioning and
indefinitely thereafter (see protocol on irradiated blood products).
Ensure pregnancy test is carried out on day -7 on all women of child-bearing potential unless they
have been sterilized or have undergone a hysterectomy.
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RIC CyFluTBI Haplo sib
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Oxford BMT Programme
SUMMARY
DAY
DRUG
Admission
Cyclophosphamide
Mesna
Fludarabine
TBI
Bone marrow/PBSCs
Pentamidine
-7
-6
-5
*
*
*
*
*
*
-4
-3
-2
*
*
*
-1
0
+1
+2
+3
+4
*
*
*
*
*
*
*
*
Cyclophosphamide
Mesna
Mycophenolate mofetil
(MMF)
Tacrolimus
***
Continue
**
Continue
*
Continue
Filgrastim (GCSF)
Guide to first line antiemetics
5HT=5HT3 antagonist
D=Dexamethasone
M=Metoclopramide
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+5
5HT 5HT
D
D
M
M
5HT 5HT
D
M
M
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5HT 5HT
D
D
M
M
May 2013
RIC CyFluTBI Haplo sib
Department of Clinical Haematology
Oxford BMT Programme
CHEMOTHERAPY AND FLUIDS
Encourage 3L oral fluids daily, give iv if oral intake insufficient
Day -6 and -5
00.00
1000mls sodium chloride 0.9% over 8 hours
08:00
500mls glucose 5% over 2 hours
10:00 (T=0)
Furosemide 20mg IV, then PRN to maintain urine
output >100mls/hr
T = 0, 3, 6 & 9
hours
Cyclophosphamide
14.5mg/kg IV od(AIBW if ABW > 125%IBW)
In 500mls sodium chloride 0.9% over 1 hour
Mesna
5.8mg/kg
(400mg vials round dose up to nearest vial)
In 100mls sodium chloride 0.9% over 15 mins
11:00 (T=1)
1000mls sodium chloride 0.9% over 6 hours
17:00 (T=7)
Days -6 to -2
11:00
Fludarabine
1000mls sodium chloride 0.9% over 6 hours
30mg/m2 IV od
In 100ml sodium chloride 0.9% over 30 mins
Day -1
TBI 2GY
1 fraction
Day 0
06.00
1000mls sodium chloride 0.9% over 6 hours
Marrow/stem cell
infusion (minimum 48
hours post Day -5
Cyclophosphamide)
•
•
•
Give hydrocortisone 100mg iv and chlorphenamine
10mg iv 15 minutes before cell infusion
Actual body weight (ABW)
Ideal body weight (IBW)
Adjusted ideal body weight (AIBW) = IBW + [(0.25) x (actual body weight – IBW)]
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RIC CyFluTBI Haplo sib
Department of Clinical Haematology
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Day +1
Pentamidine
4mg/kg/day iv (Maximum 300mg) in 100ml
sodium chloride 0.9% over 1 hour (unless
Pentamidine given within last 28 days)
Day+3 and +4
00.00
1000mls sodium chloride 0.9% over 8 hours
08:00
500mls glucose 5% over 2 hours
10:00 (T=0)
(day +3 dose to be
given between 60
and 72 hours
Cyclophosphamide
after marrow /
stem cell infusion)
Furosemide 20mg IV, then PRN to maintain urine
output >100mls/hr
T = 0, 3, 6 & 9
hours
20mg/kg
(400mg vials round dose up to nearest vial)
In 100mls sodium chloride 0.9% over 15 mins
Mesna
50mg/kg IV od (IBW) IV
In 500mls sodium chloride 0.9% over 1 hour
11:00 (T=1)
1000mls sodium chloride 0.9% over 6 hours
17:00 (T=7)
1000mls sodium chloride 0.9% over 6 hours
Day +5
•
•
•
Filgrastim
(biosimilar)
5 microgram/kg/day sc od
Until absolute neutrophil count ≥1.0x109/l for three
consecutive days
Actual body weight (ABW)
Ideal body weight (IBW)
Adjusted ideal body weight (AIBW) = IBW + [(0.25) x (actual body weight – IBW)]
DOSE MODIFICATIONS
Discuss dose reduction for fludarabine with consultant if renal function impaired.
Day -6 and -5 Cyclophosphamide: Dose is calculated using AIBW if actual body weight is > 125%
IBW.
Day +3 and +4 Cyclophosphamide: Dose is calculated using IBW
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RIC CyFluTBI Haplo sib
Department of Clinical Haematology
Oxford BMT Programme
NURSING CARE PLANS
Administration of Chemotherapy: Refer to nursing care plan N.91
Stem cell/Bone marrow infusion: Refer to nursing care plan N51 or N18
ANTI-EMETICS
Day -6 , -5, -1, +3, +4
5HT3 antagonist PO/IV od
Dexamethasone 8mg PO/IV od
Metoclopramide 20mg PO/IV qd
Day 0
5HT3 antagonist PO/IV od
Metoclopramide 20mg IV pre-cell infusion
CONCURRENT MEDICATION
Allopurinol
300mg od po for 7 days – only in patients with acute leukaemia who are
not in remission
Norethisterone
5-10mg po TDS from day 0 until platelets >50x109/l
(menstruating women only)
Fluconazole
50mg OD po from day 0 until neutrophils >1.0x109/l
(or longer if on steroids)
Pentamidine
4mg/kg/day (max 300mg) iv on day+1 and day +30
(unless started on to co-trimoxazole)
Aciclovir
For CMV Prophylaxis
If either donor or recipient or both are CMV + then:
2
500mg /m TDS iv or 800mg po QDS day -7 to day +30 then
800mg po QDS for 3 months, then 200mg TDS for further 3 months if
VZV positive
If both donor and recipient are CMV negative then consider
HSV/VZV Prophylaxis
Aciclovir dose is 250mg iv TDS or 200mg po TDS
Duration of treatment depends on HSV and VZV status of recipient:
HSV neg and VZV neg - no aciclovir needed
HSV pos and VZV neg treat for 3 months
HSV pos and VZV pos treat for 6 months
HSV neg and VZV pos treat for 6 months
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RIC CyFluTBI Haplo sib
Department of Clinical Haematology
Oxford BMT Programme
Mycophenolate Mofetil
(MMF)
Begin day +5.
15mg/kg po 8 hourly by suspension or adjusted to tablet size; IV route
can be used if PO not tolerated (same dosing as PO, given over 2 hours in
5% dextrose at a concentration of 6mg/ml). Maximum total daily dose not
to exceed 3g. If renal failure do not exceed dose of 1gm bd. No dose
adjustment for liver disease. MMF dosing should be monitored and
altered as clinically appropriate.
Stop MMF at day +35 unless active GvHD present (discuss with
consultant).
Tacrolimus (Prograf)
Begin day +5.
0.05 – 0.1mg/kg bd PO and adjust according to levels aiming for trough
level of 5-10ng/ml. IV route can be used if PO not tolerated (Intravenous
dose: third of oral dose). Aim to discontinue day +180 after
transplantation
Levels to be taken as per protocol B.5.0
Omeprazole
20mg OD from start of conditioning until platelet count >50x109/l
Filgrastim (biosimilar)
Begin day +5.
5microgram/kg/day sc od continued until absolute neutrophil count
≥1.0x109/l for three consecutive days.
INVESTIGATIONS
Daily
Alternate days
Mon/Thurs
Mon/Fri
Weekly
Monday
Other
FBC, creatinine, urea & electrolytes, weight, urinalysis
Liver function tests
Clotting, calcium, magnesium, phosphate
Group and save
Zinc, urate
Tacrolimus levels - trough level. See protocol B5.0
CMV PCR from Day+14 if either patient or donor is CMV positive
Other specimens for virology as clinically indicated.
Chest X-ray on admission then weekly and as clinically indicated
MEDICATION ON DISCHARGE (TTO’s)
Norethisterone
Fluconazole
Co-trimoxazole
Aciclovir
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Stop when platelets >50 x 10 /l
9
Stop when neutrophils >1x 10 /l (may be longer if patient on steroids)
960mg daily Mon, Wed, Fri: start when neutrophils >1x109/l and continue
until one month after immunosuppressive therapy stopped. If allergic to cotrimoxazole, pentamidine 4mg/kg (max 300mg) iv monthly
Depends on CMV/ HSV/ VZV status. Refer to page 5 of this protocol
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RIC CyFluTBI Haplo sib
Department of Clinical Haematology
Oxford BMT Programme
Omeprazole
Mycophenolate
Mofetil (MMF)
Tacrolimus
Penicillin V
Stop unless clinically indicated
15mg/kg po tds. Maximum total daily dose not to exceed 3g. If renal failure
do not exceed dose of 1gm bd. Stop on day +35.
On discharge the patient should be prescribed an oral dose to maintain trough
levels between 5-10ng/ml. Check dose with registrar or consultant. Aim to
discontinue by day +180 after transplantation in the absence of GvHD
250mg BD for life
REFERENCES
Brunstein C, Fuchs E, Carter S, Karanes C, Costa L, Wu J, Devine S, Wingard J, Aljitawi O, Cutler C,
Jagasia M, Ballen K, Eapen M, O'Donnell P; Blood and Marrow Transplant Clinical Trials Network.
Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials
using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts.
Blood. (2011) 118(2):282-8.
Summary of Product Characteristcs via www.medicines.org.uk for:
Filgrastim (Zarzio®) Last updated: 18/02/2013
Tacrolimus (Prograf®) Last updated: 18/09/2012
www.medicinescomplete.com Mesna Uses and Administration
Author(s)
Dr Robert Danby, Bone Marrow Transplant Fellow
Prof. Vanderson Rocha, Consultant Haematologist
Julia Wong, Pharmacist.
Circulation
TSSG website, patient notes.
Review
Name
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Revision
New document
Date
Version
May 2013 1.0
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Review date
May 2015
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RIC CyFluTBI Haplo sib