2 CPGchilden

Acute leukemia Lymphoma
1
2
3
4
5
6
7
8
9
10
..
..
... .
..
..
.
..
..
..
..
1
2
3
4
5
6
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(Thai Pediatric Oncology Group: ThaiPOG) /

20
2546
acute lymphoblastic leukemias 50
20 400-500 acute
lymphoblastic leukemias

3

non-hodgkin lymphoma (NHL) 48.9
NHL prognostic
1 NHL 58.92 (42.97-71.80)
NHL

national protocol 2
8

protocol
CPG ALL lymphoma
ALL & lymphoma
ALL outcome compliance expected
compliance national protocol
protocol CPG

14 2549
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National Protocol for Acute lymphoblastic leukemia (ALL)

(diagnostic investigation)
ALL (Classification)
Low risk ALL
5
6
7
High-risk ALL
10
CNS disease
testicular involvement
12
12
14
National Protocol for Acute non-lymphocytic leukemia (ANLL)

ANLL (Classification):
ANLL
14
14
Appendix
Guideline for Administration of High dose Methotrexate
Modified Toxicity Criteria for Cancer Chemotherapy
34
35
Chemotherapy Modification Guideline for Hepatic Dysfunction

Chemotherapy Modification Guideline for Renal Dysfunction
Anthracyclin Record Sheet
Guideline For Drug Preparation
36
37
38
39
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Thai National protocol for treatment of childhood acute lymphoblastic leukemia (ALL)
National protocol for treatment of childhood ALL
National protocol for treatment of childhood ALL
ALL CPG
ALL
ALL ALL outcome
compliance expected
compliance national protocol
protocol CPG

national protocol
8

2 3 protocol ALL
ThaiPOG . .
Thai national protocol

acute lymphoblastic leukemia
1. ALL (risk-adapted approach)
2. ALL (protocol-driven therapy)
3. ALL

(diagnostic investigation)
acute leukemia
1. Bone marrow aspiration Wright stain bone marrow aspiration bone
marrow biopsy
2. Cytochemistry: (MPO, PAS, Sudan black, acid phosphatase) acute lymphoblastic leukemia
cytochemistry acute myeloid leukemia
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3. ALL PAS positive ALL, MPO & sudan

black positive AML
4. Optional immunophenotypic analysis (flow cytometry) immunophenotype
ALL

ALL (Classification):
Low risk ALL
1-10 (WBC) <50,000 /ul
high-risk ALL
High-risk ALL
>10
WBC >50,000 /ul /

T-cell disease Blast cell acid phosphatase positive
mediastinal mass, 6 cm, spleen
CNS disease* at diagnosis
Testicular involvement** at diagnosis
Exclusion high-risk ALL:
<1
ALL morphology L3
ALL low & high-risk ALL
(low-risk for relapse) (high-risk for relapse)
NCI criteria (WBC)
T-cell disease high-risk ALL cytochemistry (acid phosphatase
positive) immunophenotyping T-cell disease
ALL CNS involvement high-risk ALL

CNS disease testicular involvement
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infant leukemia mature B-cell ALL high-risk ALL highrisk ALL national protocol for high-risk ALL ALL
(exclusion criteria)
Low-risk ALL
ALL low risk intensive relapse
low-risk ALL 80-90% protocol
protocol 5 phases
1) Induction of remission, 2) consolidation/CNS prophylaxis, 3) interim maintenance, 4) re-intensification, 5)
maintenance phases
Induction of remission:
4-drug induction:
Vincristine 1.5 mg/M2 IV weekly x 4 wks (days 1, 8, 15, 22)
Doxorubicin x 25 mg /M2 IV x 2 doses (days 1, 8)
L-asparaginase 6,000-10,000 IU/ M2 IM x 6 doses (days 8, 10, 12, 15, 17, 19)
Prednisolone 40 mg/M2 x 28 days (days 1-28)
Intrathecal methotrexate (dose ) x 2 doses 2 (days 1, 15)
remission 4
Supportive care:
platelet transfusion 20,000 IU
bone marrow aspiration 28 remission
protocol induction of remission 3
vincristine, L-asparaginase, prednisolone 95%
4-drug induction (long-term
remission) Doxorubicin x 6 doses reinduction
doxorubicin x 4 doses neutropenia
doxorubicin 2 doses
4-drug induction doxorubicin x 2 doses
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L-asparaiginase ALL intramuscular

subcutaneous 3 6000 IU/M2 x 9 10000 IU x 6 dose-intensity
10000 IU x 6 10000 U
8
L-asparaginase hyperglycemia, pancreatitis, pancreatic
cyst, cerebral thrombosis dose 6,000 10,000 IU/dose x 6
doses
bone marrow 14 early response
intensity early response.
Consolidation & CNS prophylaxis
High-dose methotrexate 1.5 g/M2 in 24 hours x 4 doses q 2 weeks + leucovorin 6 doses 6
intrathecal methotrexate.
ALL CNS relapse CNS prophylaxis CNS relapse
(Cranial radiation therapy, CRT) 1800 cGY
secondary brain tumor radiation intrathecal methotrexate (ITM)
low-risk ALL ITM CNS relapse intrathecal therapy
delayed CNS relapse 2-5
High-dose methotrexate (IDM) CRT consolidation
HDM 2 g/M2 MTX leucovorin rescue
MTX
dose escalation MTX 1 g/ M2 1.5 2 g M2 4
HDM 1.5 g M2 2 x 4 consolidation CNS prophylaxis
intrathecal methotrexate 2 HDM radiation
low-risk ALL CNS radiation
triple intrathecal therapy (TIT) ITM TIT
CNS toxicity ITM CNS disease
CNS relapse ( high-risk protocol)
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Delayed-intensification
Vincristine 1.5 mg/M2 IV x 3 weeks (day 1, 8, 15)
Doxorubicin x 25 mg/M2 IV x 1 doses (day 1)
L-asparaginase 6,000-10,000 IU/ M2 IM x 4 doses (days 8, 11, 15, 18)
Dexamethasone 10 mg/M2 x 21 days (days 1-22) then taper
Cyclophosphamide 1 g/M2 (day 22) followed by AraC 75 mg/M2 x 8 days (day23-26, 29-32)
6-mercaptopurine 50 mg/M2 x14 days (days 22-36)
Intrathecal methotrexate (dose ) x 2 doses 2 (during Cyclo-AraC)

delayed intenstification/ reinduction ALL low & highrisk interim maintenance x 3 ( maintenance) delayed
intenstification/ reinduction induction vincristine x 3 ,
doxorubicin 1 , dexamethasone prednisolone cyclophosphamide, AraC 6MP
Maintenance
2
Methotrexate 20 mg/M once weekly PO
2
6-mercaptopurine 50 mg/M /day PO
with pulse vincristine-prednisolone 4
Vincristine 1.5 mg/M2 IV x 1 dose
Prednisolone 40 mg/M2 x 5 days
Intrathecal methotrexate (dose ) 12
maintenance 2 3
maintenance methotrexate-6MP pulse vincristine-prednisolone
ITM 3 ITM 1
3 3
maintenance phase
low-risk ALL maintenance 2 remission 3
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10
induction of remission
relapse
intensification minimal residual disease low-risk ALL
MRD CBC relapse prognosis
national protocol
bone marrow aspiration BMA unexplained cytopenia
relapse
(Follow-up studies)
CBC
1 2
2 3
3 6
3 12
relapse
High-risk ALL
high-risk ALL 50-78%
protocol 4-drug induction, consolidation, cranial
radiation, delayed intensification/ re-induction, maintenance delayed intensification/reinduction
Induction of remission
4-drug induction:
2
Vincristine 1.5 mg/M IV weekly x 5 wks (days 1, 8, 15, 22, 29)
2
Doxorubicin x 25 mg/M IV x 4 doses (days 1, 8, 15, 22)
2
L-asparaginase 6,000-10,000 IU/ M IM x 6 doses (days 8, 10, 12, 15, 17, 19)
2
Prednisolone 40 mg/M x 28 days (days 1-28)
Intrathecal methotrexate (dose ) x 2 doses 2 (days 1, 15)
remission day 35
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11
induction of remission 4-drug delayed recovery of neutrophil 6

vincristine remission 6
Consolidation & CNS prophylaxis
2
2
Cyclophosphamide 1 g/M (day 1) followed by AraC 75 mg/M x 8 days (day2-5, 8-11)
2
6-mercaptopurine 50 mg/ M x14 days (days 1-15)
2
ANC>1,000 /ul, platelet count > 100,000/ul high-dose methotrexate 1.5 g/M in 24 hours x 4 doses q 2
weeks (day 28, 42, 56, 70) + leucovorin 6 doses 6 intrathecal methotrexate
Cranial radiation 1800 cGy in 10-12 fractions
ANC>1,000 /ul, platelet count > 100,000/ul Consolidation cyclophosphamide, AraC
6MP low-risk ALL high-dose MTX 4 CNS radiation 1800 cGy HDM
CNS relapse low-risk ALL high-dose MTX
5 g/M2 national protocol MTX
Delayed-intensification x 2 interim maintenance 3
2
Vincristine 1.5 mg/M IV x 3 weeks (day 1, 8, 15)
2
Doxorubicin x 25 mg/M IV x 1 doses (day 1)
2
L-asparaginase 6,000-10,000 IU/ M IM x 4 doses (days 8, 11, 15, 18)
2
Dexamethasone 10 mg/M x 21 days (days 1-22) then taper
2
2
Cyclophosphamide 1 g/M (day 22) followed by AraC 75 mg/M x 8 days (day23-26, 29-32)
2
6-mercaptopurine 50 mg/M x14 days (days 22-36)
high-risk ALL intensification/ re-induction 2 interim maintenance 3
cyclophosphamide, AraC 6MP 3 low-risk ALL
total doxorubicin 6 2 low-risk ALL protocol
protocol 6A Tokyo protocol long-term survival 78%
3 8 maintenance methotrexate 300 mg/M2 IV 2
intensification/ re-induction 2
national protocol for high-risk ALL
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12
Maintenance
2
Methotrexate 20 mg/M once weekly PO
2
6-mercaptopurine 50 mg/M /day PO
with pulse vincristine-prednisolone 4
2
Vincristine 1.5 mg/M IV x 1 dose
2
Prednisolone 40 mg/M x 5 days
Intrathecal methotrexate (dose ) 12 maintenance 3
low- high-risk ALL

rotating chemotherapy cyclo-AraC protocol

national protocol.
CNS disease
blast CSF
Triple Intrathecal therapy (dose ) x 1 induction 2
TIT 4 8
2
consolidation High-dose methotrexate 1.5 g/M x 4 doses q 2 weeks + leucovorin 6 doses 6
intrathecal methotrexate
Cranial radiation 1800 cGy in 10-12 fractions
dose cranial radiation 1800-2400 cGy spinal radiation 1,200
cGy triple intrathecal therapy HDM
1800 cGy high-risk ALL
testicular involvement
testicular enlargement at diagnosis ( 2 SD orchidometry) local testicular
radiation 1800 cGy induction therapy
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13
national protocol for ALL

National protocol

low-risk protocol
registry high-risk ALL protocol 5
high-risk ALL protocol (institutional protocol)
randomized controlled trial national
protocol long-term event-free survival low-risk ALL 80% high-risk ALL
60%
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14
Thai National protocol for treatment of childhood acute non-lymphocytic leukemia (ANLL)
Acute non-lymphocytic leukemia Thai pediatric oncology group
120 acute lymphoblastic leukemia
ANLL (Classification):
ANLL World Health organization 2000
histochemistry
ANLL
Acute promyelocytic leukemia with t (15;17) retinoic acid
ANLL
Protocol . BFM protocols (BFM 83) induction,
consolidation maintenance x 2 overall survival 40-50%
Protocol . induction Doxo/Idarubin + AraC, consolidation High-dose Ara-C
Mitoxanthrone + Etoposide maintenance overall survival 20-30% TPOG
adopt BFM83
remission protocol 60-70% remission consolidation
remission
CNS radiation CNS involvement maintenance
20
6 TPOG-AML-01-05 50 15
(30%) toxicity 2-3
supportive care induction
Ara-C (50 mg/M2/dose IV q12 hr= 100 mg/ M2/day) AraC 3-7 (50
mg/M2/dose IV q24 hr= 50 mg/ M2/day) ( . protocol 5-year
event free survival 38%) doxorubicin, etoposide
supportive care
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15
Indication for Bone marrow transplantation

match-sibling donor t(8;21) consolidation
acute promyelocytic leukemia t (15;17)
PML-RARA transcript
protocol All-trans retinoic acid (ATRA) ThaiPOG__APL.doc ATRA
ANLL
ATRA protocol ATRA
Thai National protocol for treatment of childhood lymphoma
ThaiPOG CPG lymphoma.pdf
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16
National Protocol for Acute Lymphoblastic Leukemia

Protocol name
Protocol for
Protocol TPOG- ALL-01-05

Low Risk ALL
Open Date
7 May 2005
Patients eligibility
Exclusion criteria
Acute lymphoblastic leukemia

Initial WBC < 50,000/mm3
Age between 1 - 10 yr.
Patients name
Hospital
T -cell characteristics; acid phosphatase positive with mediastinal mass,

huge hepatomegaly > 6 cm and/or splenomegaly below the umbilicus
CNS disease at diagnosis
Testicular involvement at diagnosis
Mature B-cell ALL (morphology L3)
Age
Sex
HN
Phase I
INDUCTION
BW
Ht
(4 weeks)
BSA
Date started
week
day
15
22
29
36
Date given
Alkalinization + prophylactic medication + sterile bowel
Prednisolone ___
_________________
Vincristine __
____ mg IV
Doxorubicin ___
___ mg IV
L-asp ___
I I I
_______ U IM (M-W-F)
MTX________mg IT*
I I I
BM aspiration remission not remission
Drug
Dosage
Day
Prednisolone
40 mg/m /day
1-28 then taper off in 2 wks.
Vincristine
1.5 mg/m IV push
1, 8, 15, 22
Doxorubicin
25 mg/m IV push
1, 8
2
L-asparaginase
6,000-10,000 unit /m IM M-W-F
8, 10, 12, 15, 17, 19
MTX IT*
age adjusted dose intrathecal
1, 15
Prophylactic drugs & Sterile Bowel
Sodamint
1 tab PO BID (<5yr) or TID (>5yr)
First 2 weeks
Allopurinol (100 mg)
10 mg/kg/day divided BID-QID
First 2 weeks
Clotrimazole troche (10 mg)

or nystatin suspension
1 tab PO TID (>5yr) or

nystatin 2 ml PO QID (<5yr)
1-28
* age adjusted dose intrathecal chemotherapy for Methotrexate
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1-1.9 yrs
2-2.9 yrs
>3 yrs
10
12
17
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

Phase II CONSOLIDATION & CNS PROPHYLAXIS (7 weeks) Date started
week
day
15
22
29
36
43
50
Date given
6-MP(50 mg) ___ tab q hs
mg IV drip 24 hr
Hydration & alkalinization
tab IV or po q 6 hr X 6 doses
Methotrexate
Leucovorin
MTX
mg*
See high dose MTX guideline

Drug
Dosage
Day
2
Methotrexate
1.5 gm /m IV drip in 24 hr
1, 15, 29, 43
(see Appendix)
2
Leucovorin (start at 12 hr after stop MTX)
15 mg/m IV or PO q 6 hr x 6 doses
2, 16, 30, 44
MTX IT*
1, 15, 29, 43
6-MP (50mg)
50 mg /m / day PO q hs
Phase III INTERIM - MAINTENANCE PHASE
Date started
week1
/
2
2-2.9 yrs
>3 yrs
10
12
(3 months)
, week 5
, week 9
Pred (5 mg) ____________
MTX (2.5 mg) ___ tab wkly
Vincristine _____ mg IV
1-1.9 yrs
week
1-56
10
11
12
Pulse Treatment
q 4 weeks
Maintenance
Dosage
6-MP (50mg)
Methotrexate (MTX)
20 mg /m / week PO
Vincristine
1.5 mg/m IV day 1
Prednisolone
40 mg/m day PO x 5 days
Cotrimoxazole (
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2
2
5 mg/kg/day PO bid 2-3 day/wk
18
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

Phase IV DELAYED - INTENSIFICATION (7 weeks)
week
day
1
1
2
8
3
15
Date started
4
22
5
29
6
36
IIII
IIII
7
43
Date given
Dexamethasone ___________
Day 1-21
Vincristine ______ mg IV
Doxorubicin ______ mg IV
L-asp ______ U IM
I I
I I
Ara-C _______mg IV
CTX _______mg IV
6-MP _________________
MTX _______ mg IT*
Drug
Day 29-42
Dosage
Day
2
Dexamethasone
10 mg/m /day PO
1-21 then taper off
Vincristine
1.5 mg/m IV push
1, 8, 15
25 mg/m IV push
Doxorubicin
1
2
6,000-10,000 unit /m IM
L-asparaginase
Cyclophosphamide (CTX)
Cytosine arabinoside (Ara-C)
1,000 mg/m IV drip in 1 hr.
8, 11, 15, 18
29
29-32, 36-39
75 mg/m IV push
6-MP (50mg)
29-42
MTX IT*
1, 29
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1-1.9 yrs
2-2.9 yrs
>3 yrs
10
12
19
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

Phase V
MAINTENANCE
Date remission
Total 2.5 yrs. after remission in girls

Total 3 yrs. after remission in boys
_
Date started maintenance
week
MTX _______ mg IT*
Vincristine ____ mg IV
Pred (5 mg) ____________
/
10
11
12
Record date given
wk 1 _____________ wk 2 _____________ wk 3 ___________
Ht _____ Wt ______
wk 13 _____________ wk 17_____________ wk 21 ___________
Ht _____ Wt ______
wk 25 _____________ wk 29_____________ wk 33 ___________
Ht _____ Wt ______
wk 37 _____________ wk 41_____________ wk 45 ___________
Ht _____ Wt ______
wk 49 _____________ wk 53_____________ wk 57 ___________
Ht _____ Wt ______
wk 61 _____________ wk 65_____________ wk 69 ___________
Ht _____ Wt ______
wk 73 _____________ wk 77_____________ wk 81 ___________
Ht _____ Wt ______
wk 85 _____________ wk 89_____________ wk 93 ___________
Ht _____ Wt ______
wk 97 _____________ wk 101____________ wk 105 __________
Ht _____ Wt ______
wk 109 ____________ wk 113____________ wk 117 __________
Ht _____ Wt ______
wk 121 ____________ wk 125____________ wk 129 __________

END OF THERAPY Date
Pulse Treatment
q 4 weeks
Maintenance
Dosage
6-MP (50mg)
Methotrexate (MTX)
20 mg /m / week PO
Vincristine
1.5 mg/m IV day 1
Prednisolone
Cotrimoxazole (
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2
2
1-1.9 yrs
2-2.9 yrs
>3 yrs
10
12
20
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

POST TREATMENT GUIDELINES
Guidelines for follow up patients post treatment
1. 1st year :
PE, CBC q 2 months.
2. 2nd year :
PE, CBC q 3 months.
3. 3rd year :
PE, CBC q 6 months
4. After 3rd year :
PE, CBC q 12 months
Bone marrow aspiration

1. Before discontinue chemotherapy
2. Unexplained cytopenia
3. Sign & symptom of relapse
Guideline for bactrim prophylaxis
1. Started when consolidation
2. Bactrim is given 5 mg of TMP /kg/day divided bid 2-3 times per week (M-W-F, F-Sa-Su, or Sa-Su)
3. Stop bactrim prophylaxis 1 week before and during CNS prophylaxis with high-dose methotrexate
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21
National Protocol for Acute Lymphoblastic Leukemia
Protocol name
Protocol for
Open Date

High Risk ALL and T-cell NHL or LBL stage III/IV
7 May 2005
Exclusion criteria
1. Acute lymphoblastic leukemia with any of the following characteristics

3
Initial WBC > 50,000/mm
Age > 10 yr or < 1 yr
T -cell characteristics; acid phosphatase +ve with mediastinal mass,
huge hepatomegaly >6 cm and/or splenomegaly below the umbilicus
CNS disease at diagnosis**
Testicular involvement at diagnosis***
2. Non-Hodgkin lymphoma: T-cell or lymphoblastic type, stage III / IV
Patients name
Age
Hospital
HN
Phase I
INDUCTION
BW
Mature B-cell ALL

(see SNC protocol)
Sex
Ht
(6 weeks)
BSA
Date started
week
day
15
22
29
36
Date given
Prednisolone ___
_________________
Vincristine __
____ mg IV
Doxorubicin ___
___ mg IV
I I I
I I I
T**
L-asp ___
_______ U IM (M-W-F)
MTX________mg IT*
T**
BM aspiration remission not remission
**CNS disease (positive blast cells in CSF) - add age adjusted dose Triple-T IT weekly until blast cells negative 2 consecutive weeks (at
least 4 doses / maximum 8 doses)
***Testicular involvement - add testicular radiation total dose 1800 cGy.
Drug
Dosage
Day
2
Prednisolone
40 mg/m /day
1-28 then taper off in 2 wks.
Vincristine
1.5 mg/m IV push
1, 8, 15, 22
Doxorubicin
25 mg/m IV push
1, 8, 15, 22
2
L-asparaginase
6,000-10,000 unit /m IM M-W-F
MTX IT*
Age-adjusted dose intrathecally
*adjust dose according to age

**Triple intrathecal for CNS disease
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Intrathecal medications
MTX
ARA-C
Hydrocortisone
8, 10, 12, 15, 17, 19

1, 15
1-1.9 yrs
8
20
8
2-2.9 yrs
10
25
10
>3 yrs
12
30
15
22
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

Phase II CONSOLIDATION (12 weeks)
week
day
1
1
2
8
Date started
3
15
4
22
5
29
6
36
____/_____/______
7
43
8
50
9
57
10
64
11
71
12
78
Date given
6-MP _____ tab daily
CTX ________mg IV
Ara-C _________mg IV
Day 1-14
Day 29-85
IIII
IIII
#
Leucovorin____mg q 6hr x 6
MTX ______ mg IV drip 24 hr
Hydration & alkalinization
MTX _______ mg*
Start MTX IV drip when ANC > 1000 /L & Plt > 100,000 /L
See high dose MTX guideline
Drug
Dosage
Day
6-MP (50mg)
50 mg/m day PO
1-14, 29-85
1,000 mg/m IV drip in 1 hr.
75 mg/m IV push
2-5, 8-11
Methotrexate (MTX)
1.5 gm /m IV drip in 24 hr
29, 43, 57, 71
Leucovorin (start at 12 hr after stop MTX)
15 mg/m IV or PO q 6 hr x 6 doses
30, 44, 58, 72
MTX IT*
1, 29, 43, 57, 71
Phase III
CNS PROPHYLAXIS# (3 weeks)
Cranial radiation
Date
1-1.9 yrs
2-2.9 yrs
>3 yrs
10
12
Date started
(1800 cGy in 10-12 fraction)

/
to
Infant leukemia Postpone CNS prophylaxis until age > 3 year
**Initial CNS involvement - add age adjusted dose Triple-T IT weekly x 2 doses
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Patients name
Hospital
HN
Phase IV
BW
Age
Sex
Ht
BSA
1st INTERIM - MAINTENANCE PHASE
Date started
week 1 ____/____/___
2
(12 weeks)
week 5 ____/____/___ week 9 ____/____/___
week
Pred (5 mg) ____________
10
11
12

Pulse Treatment
q 4 weeks
Maintenance
Dosage
6-MP (50mg)
50 mg /m2 / day PO q hs
Methotrexate (MTX)
20 mg /m / week PO
Vincristine
1.5 mg/m IV day 1
Prednisolone
Cotrimoxazole (
1st DELAYED - INTENSIFICATION PHASE (12 weeks) Date started____/____/___
Phase V
week
day
Date given
1
1
2
8
Dexamethasone _________ tab PO
3
15
4
22
5
29
6
36
IIII
IIII
Day 1-21
L-asp ______ U IM (M- Th)
Ara-C _______mg IV
CTX _______mg IV
6-MP ______ tab PO
MTX _______ mg IT*
Day 29-42
T#
T#
Drug
Dosage
Day
Dexamethasone (0.5 mg tab)
10 mg/m /day PO divided tid
Vincristine
1.5 mg/m IV push
1, 8, 15
25 mg/m IV push
Doxorubicin
1
2
6,000-10,000 unit /m IM M- Th
L-asparaginase (L-asp)
1-21 then taper off
1,000 mg/m IV drip in 1 hr
8, 11, 15, 18
29
29-32, 36-39
75 mg/m IV push
6-MP (50mg)
50 mg/m day PO hs x 14 days
29-42
MTX IT*
1, 29
Age-adjusted dose triple drug intrathecal in CNS disease until total 10 doses
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24
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA
Phase VI 2nd INTERIM - MAINTENANCE PHASE (12 weeks)

Date started
week 1 ____/____/___ week 5 ____/____/___ week 9 ____/____/___
week
Pred (5 mg) ____________
10
11
12

Pulse Treatment
q 4 weeks
Maintenance
Dosage
6-MP (50mg)
Methotrexate (MTX)
20 mg /m / week PO
Vincristine
1.5 mg/m IV day 1
Prednisolone
Cotrimoxazole (
Phase VII 2nd DELAYED - INTENSIFICATION PHASE (12 weeks) Date started____/____/___
week
day
1
1
2
8
3
15
4
22
5
29
6
36
IIII
IIII
Date given
Dexamethasone _________ tab PO
Day 1-21
L-asp ______ U IM (M- Th)
Ara-C _______mg IV
CTX _______mg IV
6-MP ______ tab PO
MTX _______ mg IT*
Drug
Day 29-42
#
Dosage
Dexamethasone (0.5 mg tab)
Day
2
10 mg/m /day PO divided tid
1-21 then taper off
Vincristine
1.5 mg/m IV push
1, 8, 15
Doxorubicin
25 mg/m IV push
1
2
L-asparaginase (L-asp)
6,000-10,000 unit /m IM M- Th
8, 11, 15, 18
1,000 mg/m IV drip in 1 hr
29
29-32, 36-39
75 mg/m IV push
6-MP (50mg)
50 mg/m day PO hs x 14 days
29-42
MTX IT*
1, 29
Age-adjusted dose triple drug intrathecal in CNS disease until total 10 doses
Patients name
Age
2549
Sex
25
Hospital
HN
BW
Ht
BSA

Phase VIII
MAINTENANCE
Date remission
Total 3 yrs after remission
Date started maintenance
week
MTX _______ mg IT*
Vincristine ____ mg IV
Pred (5 mg) ____________
10
11
12
Record date given
wk 1 _____________ wk 5 _____________ wk 9 ___________
Ht _____ Wt ______
wk 13 _____________ wk 17_____________ wk 21 ___________
Ht _____ Wt ______
wk 25 _____________ wk 29_____________ wk 33 ___________
Ht _____ Wt ______
wk 37 _____________ wk 41_____________ wk 45 ___________
Ht _____ Wt ______
wk 49 _____________ wk 53_____________ wk 57 ___________
Ht _____ Wt ______
wk 61 _____________ wk 65_____________ wk 69 ___________
Ht _____ Wt ______
wk 73 _____________ wk 77_____________ wk 81 ___________
Ht _____ Wt ______
wk 85 _____________ wk 89_____________ wk 93 ___________
Ht _____ Wt ______
wk 97 _____________ wk 101____________ wk 105 __________

END OF THERAPY Date
Pulse Treatment
q 4 weeks
Maintenance
Dosage
6-MP (50mg)
Methotrexate (MTX)
20 mg /m / week PO
Vincristine
1.5 mg/m IV day 1
Prednisolone
Cotrimoxazole (
2549
2
2
1-1.9 yrs
2-2.9 yrs
>3 yrs
10
12
26
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA

1. 1st year :
PE, CBC q 2 months.
2. 2nd year :
PE, CBC q 3 months.
3. 3rd year :
PE, CBC q 6 months
4. After 3rd year :
PE, CBC q12 months

1. Before stop chemotherapy
1. Start when consolidation
3. Stop bactrim prophylaxis 1-week before and during CNS prophylaxis with high-dose methotrexate
Reimmunization
-post off treatment 1 yr.
2549
27
National Protocol for Acute Non-Lymphoblastic Leukemia
Protocol name
Protocol TPOG-AML-01-05
Modified from
Open Date
Protocol AML-BFM-83: Med Pediatr Onc 1993; 21:8-13

15 October 2005
Exclusion criteria
Acute non-lymphoblastic leukemia
Relapsed ANLL
Patients name
Hospital
HN
BW
Phase I
INDUCTION
(6 weeks)
Age
Sex
Ht
BSA
Date started
day
Date given
Cytosine Arabinoside _____ mg IV infusion in 24 hr
Cytosine Arabinoside _____ mg IV q 12-24 hr
Adriamycin ___
___ mg IV
Etoposide _______ mg IV drip in I hr

MTX____
BM aspiration
_ mg* IT
when >day 15 and ANC > 1,000 /uL
____/____/____
Results : in remission (blast < 5%) Phase II consolidation

Not in remission (blast > 5%) If patient can tolerate chemotherapy, repeat Phase I (date _____ / ____ / _____)
If patient cannot tolerate chemotherapy Phase II consolidation
CNS disease MTX IT at week 1; then followed by Ara-C IT weekly until CSF -ve
Drug
Dosage
Day
Cytosine Arabinoside
100 mg/m /day IV infusion in 24 hr
1, 2
50 mg/m /dose IV q 12-24 hr x 6 days (6-12doses)

2
25 mg/m IV push
Adriamycin
3, 4, 5, 6, 7, 8
3, 4, 5
Etoposide
150 mg / m IV drip in 1 hr
6, 7, 8
Methotrexate IT
Prophylactic drugs & Sterile Bowel
Sodamint
1 tab PO BID (<5yr) or TID (>5yr)
First 2 weeks
Allopurinol (100 mg)
10 mg/kg/day divided BID-QID
First 2 weeks
Clotrimazole troche (10 mg)

or nystatin suspension
1 tab PO TID (>5yr) or

nystatin 2 ml PO QID (<5yr)
1-28
* age adjusted dose intrathecal chemotherapy
Patients name
drug
<1 yr
1-2 yr
2-3 yr
>3 yr
Methotrexate
10
12
Ara-C
15
20
30
50
Age
2549
Sex
28
Hospital
HN
BW
Ht
BSA
Phase II
CONSOLIDATION (8 weeks)
Date started
week
day
15
22
29
36
43
50
57
IIII
IIII
IIII
IIII
Date given
Prednisolone ______________________
Day 1-28
6-TG __________________________
Day 1-56
Vincristine ______ mg IV push
Adriamycin ______ mg IV push
IIII
IIII
IIII
IIII
Ara-C ___ mg in piggy back 100 ml IV drip
CTX ____ mg IV drip in 30 min

Ara-C ______ mg IT*
Note febrile neutropenia ANC> 1,000-1,500 /uL
Drug
Dosage
Prednisolone (5mg)
40 mg /m /day PO divided tid-qid
6-thioguanine (6-TG 40 mg)
Day
2
1-28 then taper off
1-56
60 mg /m PO daily
2
Vincristine
1.5 mg /m IV weekly
Adriamycin
1, 8, 15, 22
1, 8, 15, 22
week 1-8
30 mg /m IV weekly
Cytosine Arabinoside (Ara-C)
75 mg/ m IV drip in 30 min, 4 days/wk x 8 wk
500 mg/m IV drip in 30 min with hydration
29, 57
Ara C intrathecal
Age-adjusted dose*
35, 42, 49, 56
Co-trimoxazole
5 mg/kg/day divided BID
Fri-Sat-Sun
Phase III
CNS PROPHYLAXIS **
4 weeks
Date started
**Only for Patients with initial CNS involvement and age > 2 years only
Week
Date
2
6-TG ___________________ (60 mg/m day PO)
Day 1-14
Cranial Irradiation _______ cGy x 10 fractions

MTX ___________ mg IT x 4 times
Date given
CSF examination: Gross appearance
Pandy / Nonne
Benedict test
Cells (RBC / WBC)
Patients name
Hospital
HN
BW
2549
Age
Sex
Ht
BSA
29
Phase IV
MAINTENANCE PHASE (Total duration 2 years) Date Started ____/____/___
Give the following courses q 4 weeks
Drug
Dosage
Course A
(For month 1, 3, 5, 7)
Adriamycin
6-Thioguanine
_____________________
Day 1-4
25 mg/m IV push
_____________________
Day 1
_____________________
Daily
_____________________
Fri-Sat-Sun
_____________________
Day 1-4
_____________________
Daily
40 mg/m /day IV x 4 days
60 mg/m /day PO
2
Co-trimoxazole
Course B
Day
5 mg/m /day divided BID
(For month 2, 4, 6, and 8 24 )
6-Thioguanine
40 mg/m /day IV x 4 days

60 mg/m /day PO
2
Co-trimoxazole
5 mg/m /day divided BID
_____________________
Fri-Sat-Sun
LP + Ara-C IT
Age adjusted dose
_____________________
q 2 months
BM aspiration * (Optional)
q 4 months
BUN, creatinine, LFT
q 4 months
Schedule:
Month
Chemotherapy course:
BMA*, blood chem.
LP+ Ara C____ mg IT
Month
10
11
12
13
14
15
16
Chemotherapy
BMA*, blood chem.
LP+ Ara C____ mg IT
Month
17
18
19
20
21
22
23
24
Chemotherapy
BMA*, blood chem.
LP+ Ara C____ mg IT
Date
Date
Date
END OF THERAPY Date
2549
30
Patients name
Hospital
HN
BW
Age
Sex
Ht
BSA
1st year : PE, CBC q 2 months.

2nd year : PE, CBC q 3 months.
3rd year : PE, CBC q 6 months
After 3rd year : PE, CBC q 12 months

1. Before discontinue chemotherapy
1. Start when consolidation
3. Stop bactrim prophylaxis 1 week before and during CNS prophylaxis with high-dose methotrexate
Reimmunization
-post off treatment 1 yr.
Evaluation for long term side effects yearly
1. Growth chart
2. Learning problems
3. Endocrine evaluation and consultant when enter adolescent
4. Secondary malignancy
2549
31
Appendix
Guideline for Administration of High dose Methotrexate > 1000 mg/m2

2549
32
Guideline for Administration of High dose Methotrexate > 1000 mg/m2

1.
2.
3.
4.
CBC : WBC > 3000/L, ANC > 1000/L, Plt > 100,000/L
mucositis oral ulcers
BUN, creatinine creatinine clearance, dose creatinine clearance (Page 4)
MTX toxicity
cotrimoxazole, salicylate, pyrimethamine, NSAIDs, penicillin, live virus vaccine, probenecid
5. Hydration and alkalinization
- high dose hydration 5%D in N/2 + NaHCO3 20-40 mEq/L + KCL
10mEq/L IV rate 125ml/m2/hr (2x maintenance rate) 2 . urine output >
3 ml/kg/hr
- infusion urine Sp. gr < 1.010 urine pH > 6.5
- fluid rate methotrexate
IV fluid 125 ml/M2/hr (3000 ml/M2/day) 24-48 .
urine output > 2 ml/kg/hr
6. Methotrexate administration (Total dose 1.5 gm/M2/24 hour)
Methotrexate 150 mg/M2 (10% of total dose) in 5%D N/2 100ml IV in 1 hour
Methotrexate 1350 mg/M2 (90% of total dose) in 5%D N/2 500 ml IV drip in 23 hr
( rate IV drip rate IV + chemo = 125 ml/M2/hr)
7. inadequate urine output > 3 hr fluid overload
- Mannitol 200 mg/kg in NSS 25 ml IV over 15-60 min
- Furosemide 0.5-1 mg/kg IV push
8. Leucovorin rescue leucovorin dose MTX 36 ( MTX 12
) 15 mg/M2q 6 hr x 6 doses < 15 mg 1 (15
mg) > 15 mg 2
mucositis methotrexate leucovorin rescue
3 doses q 6 hr dose methotrexate
9. nephrotoxicity methotrexate
2549
33
Site
Blood
Infection
Renalbladder
Liver
Pancreas
GI
Nervous
system
pulmonary
cardiac
measure
WBC x 103/L
ANC x 103/L
hemorrhage
thrombosis
fever
Infection
BUN
Creatinine
Cr. clearance
Electrolytes
Proteinuria
Hematuria
SGOT
SGPT
Alk phos
Total bili
clinical
Amylase
Glucose (mg/dl)
U/S pancreas
Vision
Mild 1
3.0-3.9
1.5-1.9
minimal
Lab change
38-40 oC
mild
20-39
<1.5 x N
<1.5 x N
Mild, no S&S
1+
micro
<2.5 x N
<2.5 x N
<2.5 x N
Toxicity grade
Moderate 2
2.0-2.9
1.0-1.4
Moderate
peripheral
>40 oC, <72hr
moderate
40-59
1.5-2 x N
1.5-2 x N
mild S&S
2+ - 3+
gross
2.6 - 5 x N
2.6 - 5 x N
2.6 - 5 x N
<1.5 x N
WNL
WNL
normal
<1.5 x N
116-160
Sonolucency
(SL)
mild
erythema, mild
soreness
2-3 /day
Mild ileus
mild
DTR mild
paresthesia,
constipation
Headache,
lethargy
tachypnea
80-89
10-20%
ST-T change
sinus tachy
24-30
Transient HT
1.5-2 x N
161-250
Localized SL,
size
intake
Painful/edema
can eat
4-6 /day
moderate
moderate
severe paresthesia &
constipation
Somnolence, confused, cord
dysfunction
tremor, depress
dyspnea
O2 required
65-79
50-64
21-35%
36-50%
Atrial arrhyth,
Multifocal
unifocal PVC
PVCs
20-24
<20
Persistent HT
CHF mild
Nausea & vomit

Stomatitis
none
none
Diarrhea
Constipation
Abdominal pain
Peripheral
none
none
none
none
CNS
none
Clinical
pAO2
Vital capacity
EKG
normal
> 90
WNL
Normal
Echo %FS
clinical
Normal >30
normal
Objective
none
No change
Subjective
No change
Allergy
Hearing
WNL 0
>4.0
>2.0
none
none
<38oC
none
<20
WNL
WNL
WNL
neg
neg
WNL
WNL
WNL
WNL
Normal
2549
Rash, fever
20-40db
loss<4kHz
Loss on
audiometry
urticaria
>40 db loss
>4kHz
Tinnitus, soft
speech
Severe 3
1.0-1.9
0.5-0.9
Vital organs
Large vv.
> 72 hr
severe
60-79
2-5 x N
2-5 x N
Severe S&S
4+
with clot
5.1 20 x N
5.1 20 x N
5.1 20 x N
1.5 - 3 x N
precoma
2-5 x N
251-500
Generalized
SL
Cant eat
Cannot eat or
drink
7-10 /day
severe
severe
Severe
weakness
bronchospasm
>40 db loss 2
kHz
correctable c
hearing aid
Subtotal loss
Unacceptable 4
<1.0
<0.5
Life threatening
stroke
> 7 days
Life threatening
>80, uremia
>5 x N
>5 x N
Life threatening
Nephrotic syn
massive
>20.0 x N
>20.0 x N
>20.0 x N
>3.0 x N
Hepatic coma
>5 x N
>500
Pseudo-cyst,
hemorrhagic
Require TPN
Require TPN
> 10, bloody
> 96 hr
Need sedation
Paralysis, resp
dysfunction
Seizure, coma,
SIADH
Assist ventilator
<49
>51%
Severe CHF,
cardiac temponard
anaphylaxis
>40 db loss <2
kHz
deafness
blindness
34
Criteria for Liver Toxicity
SGOT
SGPT
Alk phos
Total bili
Clinical
Grade 0
WNL
WNL
WNL
WNL
Grade 1
< 2.5 x N
< 2.5 x N
< 2.5 x N
Grade 2
2.6 5 x N
2.6 5 x N
2.6 5 x N
< 1.5 x N
Grade 3
5.1 20 x N
5.1 20 x N
5.1 20 x N
1.5 3 x N
precoma
Grade 4
> 20.0 x N
> 20.0 x N
> 20.0 x N
> 3.0 x N
hepatic coma
Modification of Drug with Liver Toxicity
Drug
L-Asparaginase
6-MP, 6-TG
Methotrexate
BCNU, CCNU
Grade 1
100%
100%
100%
Restart 50%
Grade 2
100%
Restart 50%
Restart 50%
Grade 3
stop
stop
stop
stop
Grade 4
stop
stop
stop
stop
Modification of Drug with liver-dependent metabolism
Bili (mg/dL) / SGOT (U/mL)

Vincristine, Vinblastine
VP-16
Adriamycin, Idarubicin
Actinomycin D
Methotrexate
Cyclophopshamide
CCNU, BCNU
5-FU
Cytosine arabinoside
DTIC, procarbazine
< 1.5 / < 60

100%
100%
100%
100%
100%
100%
100%
100%
100%
100%
2549
1.5 3.0 / 60 - 180 3.1 5.0 / > 180

50%
stop
50%
stop
50%
25%
50%
25%
50%
25%
100%
25%
100%
100%
100%
100%
100%
100%
100%
100%
> 5.0
stop
stop
stop
stop
stop
stop
stop
stop
stop
stop
35
Determination of creatinine clearance (CrCl)
Cockcroft-Gault formula
Male
Creatinine clearance (ml/min) =
Female
Creatinine clearance (ml/min) =
weight (kg) x (140 - age)

72 x serum creatinine (mg/dl)
weight (kg) x (140 - age) x 0.85
72 x serum creatinine (mg/dl)
CrCl (ml/min)
Drug
100
90
80
70
60
50
40
30
20
10
Asparaginase
100
100
100
100
Bleomycin
100
100
100
100
75
75
75
Carboplatin
100
100
100
100
Carmustine
100
100
100
100
Cisplatin
100
100
100
100
50
50
50
Cyclophosphamide
100
100
100
100
100
75
75
75
75
50
Etoposide
100
100
100
100
100
75
75
75
75
50
Hydroxyurea
100
100
100
100
100
100
100
100
100
20
Ifosfamide
100
100
100
100
100
75
75
75
75
50
Methotrexate
100
100
100
100
50
50
50
Mitomycin C
100
100
100
100
75
75
75
75
75
50
Procarbazine
100
100
100
100
100
100
100
topotecan
100
100
100
100
50
50
50
50
50
Calculate AUC *
dose :
Busulfan, Doxorubicin, 5-FU, idarubicin, Melphalan, 6-TG,

Vinblastin, Vincristine
recommendation renal impairment : Cytarabine, Dactinomycin, Ifosfamide,
6-MP, fludarabine
2549
36
Patients Name__________________________________Age_______Sex________
Diagnosis
Protocol
BW___________________Ht_________________BSA________________________
Anthracyclin used
Date
Dose
mg
Mg/m2
2549
Cumulative dose
mg
EKG/Echo
Mg/m2

Classification
Antibiotics
Generic name
Doxorubicin HCL
Plant alkaloids
Vincristine SO4
(VCR)
Etoposide (VP-16)
Topoisomerase
inhibitors
Antimetabolites
Alkylating
agents
Miscellaneous
Size
10mg
50mg
Final preparation
0.9%NSS 0.5mg/ml IV push
0.9%NSS 100ml IV drip
1mg
0.9%NSS to 1mg/10ml
Vepesid
Lastet
50mg
100mg
5%D/W ~ 0.6mg/ml IVdrip in 1hr

( 1 mg/ml)
Methotrexate(MTX)
Methotrexate
Abitrexate
50mg/5ml
50mg/2ml
Cytosine arabinoside
(ARA-C)
Cytosar
Cytarine
100mg
500mg
Cyclophosphamide
(CTX)
Endoxan
Alkyloxan
200mg
500mg
1000mg
<150 mg
+ 0.9%NSS 100 ml IV drip
>150 mg
+ 5%D NSS/2 500 ml IV drip
0.9%NSS to 2ml IT
0.9%NSS to 10ml IV push
0.9%NSS 100ml IV drip in 1-3 hr
5%D NSS/2 500ml Continuous
drip 24hr.
0.9%NSS to 8ml IT
0.9%NSS 10mg/ml IV drip
0.9%NSS 10mg/ml IV push
Ifosfamide
Holoxan
500mg
1000mg
100mg
30mg
50mg
400mg
10,000 U
5,000 U
Hydrocortisone
Cacium Folinate
Mesna
L-asparaginase
2549
Trade names
Adriblastina
Adriamycin
(ADR)
39
Leucovorin
calcium
Uromitexan
Leunase
0.9%NSS 10mg/ml IV drip
Stability
48hr at 4C
24hr at room
temperature
Avoid sun exposure
7days at 4C
48 hr(0.4mg/ml)
8 hr (0.6 mg/ml)
2 hr (1 mg/ml)
48hr
Vigorously hydrate
for high dose
*See High dose MTX
protocol
48hr at 4C
48hr at 4C
6hr.at RT
24hr. at 4C
0.9%NSS to 5ml IT
0.9%NSS to 10mg/ml IV push
5% D/W to 20ml IV drip in 15min
Dilute with NSS to 2 ml IM
Special consideration
Strong vesicant
Cardiotoxic
Echo when accumulative
dose >300mg/m2
Neurotoxic,Vesicant
Max dose 2 mg/day
Hypersensitivity
Record V/S q 15 mins.
Hemorrhagic cystitis
Vigorous hydration +
Mesna for high dose
protocol (>1g/m2)
Same as CTX
Start first dose at 6 hr after

stop MTX
24hr at RT
8 hr at 4C

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Acute leukemia Lymphoma

(Thai Pediatric Oncology Group: ThaiPOG) /

National Protocol for Acute lymphoblastic leukemia (ALL)

Low risk ALL

National Protocol for Acute non-lymphocytic leukemia (ANLL)

Chemotherapy Modification Guideline for Hepatic Dysfunction

3. ALL PAS positive ALL, MPO & sudan

ALL CNS involvement high-risk ALL

Vincristine 1.5 mg/M2 IV weekly x 4 wks (days 1, 8, 15, 22)

Doxorubicin x 25 mg /M2 IV x 2 doses (days 1, 8)

Prednisolone 40 mg/M2 x 28 days (days 1-28)

Intrathecal methotrexate (dose ) x 2 doses 2 (days 1, 15)

L-asparaiginase ALL intramuscular

Vincristine 1.5 mg/M2 IV x 3 weeks (day 1, 8, 15)

Doxorubicin x 25 mg/M2 IV x 1 doses (day 1)

L-asparaginase 6,000-10,000 IU/ M2 IM x 4 doses (days 8, 11, 15, 18)

Dexamethasone 10 mg/M2 x 21 days (days 1-22) then taper

6-mercaptopurine 50 mg/M2 x14 days (days 22-36)

Intrathecal methotrexate (dose ) x 2 doses 2 (during Cyclo-AraC)

induction of remission 4-drug delayed recovery of neutrophil 6

low- high-risk ALL

national protocol for ALL

Indication for Bone marrow transplantation

National Protocol for Acute Lymphoblastic Leukemia

Protocol TPOG- ALL-01-05

Acute lymphoblastic leukemia

T -cell characteristics; acid phosphatase positive with mediastinal mass,

BM aspiration remission not remission

1-28 then taper off in 2 wks.

1.5 mg/m IV push

6,000-10,000 unit /m IM M-W-F

8, 10, 12, 15, 17, 19

age adjusted dose intrathecal

Prophylactic drugs & Sterile Bowel

1 tab PO BID (<5yr) or TID (>5yr)

Allopurinol (100 mg)

10 mg/kg/day divided BID-QID

Clotrimazole troche (10 mg)

1 tab PO TID (>5yr) or

* age adjusted dose intrathecal chemotherapy for Methotrexate

Protocol TPOG- ALL-01-05

Hydration & alkalinization

See high dose MTX guideline

Leucovorin (start at 12 hr after stop MTX)

age adjusted dose intrathecal

* age adjusted dose intrathecal chemotherapy for Methotrexate

Phase III INTERIM - MAINTENANCE PHASE

Pred (5 mg) ____________

MTX (2.5 mg) ___ tab wkly

6-MP(50 mg) ___ tab q hs

1.5 mg/m IV day 1

40 mg/m day PO x 5 days

5 mg/kg/day PO bid 2-3 day/wk

Protocol TPOG- ALL-01-05

1-21 then taper off

1.5 mg/m IV push

1,000 mg/m IV drip in 1 hr.

50 mg/m day PO x 14 days

age adjusted dose intrathecal

* age adjusted dose intrathecal chemotherapy for Methotrexate

Protocol TPOG- ALL-01-05

Total 2.5 yrs. after remission in girls

MTX _______ mg IT*

wk 1 _______ wk 2 _ wk 3 _____

wk 13 _______ wk 17_ wk 21 _____

wk 25 _______ wk 29_ wk 33 _____

wk 37 _______ wk 41_ wk 45 _____

wk 49 _______ wk 53_ wk 57 _____

wk 61 _______ wk 65_ wk 69 _____

wk 73 _______ wk 77_ wk 81 _____

wk 85 _______ wk 89_ wk 93 _____

wk 97 ___ wk 101 wk 105

wk 109 __ wk 113 wk 117

wk 121 __ wk 125 wk 129

week 5 __//_ week 9 __//_

1st DELAYED - INTENSIFICATION PHASE (12 weeks) Date started__//_