Treatment for Childhood ALL in Taiwan: a TPOG 2002 Study Emphasizing the

Optimal Reinduction Therapy

報告者：李孟如

指導者：梁德城

2016/9/241

馬偕醫院 臺大醫院 林口長庚 高雄醫大 彰基 台北榮總

梁德城劉希哲葉庭吉

林東燦周獻堂楊永立

林凱信盧孟佑張修豪

洪悠紀楊兆平江東和陳世翔

邱世欣林佩瑾廖優美

王士忠林明燦

洪君儀顏秀如

義大醫院 中國醫大 成大醫院 高雄長庚 和信醫院 北醫雙和 台中榮總

張泰琮 彭慶添巫康熙

陳建旭鄭兆能

蕭志誠沈俊明

陳博文陳榮隆

陳淑惠 張德高

萬芳醫院 中山醫院 高雄榮總 童綜合醫院 國泰醫院 新光醫院 花蓮慈濟

王錦莉 趙玉華 張裕享 錢新南 謝玉林 何宛玲 楊尚憲

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Role of reinduction

BFM group

• in high-risk patients

ALL-BFM 83 trial

• extended in low-risk patients

St. Jude 13B protocol

• 6-week reinductiontherapy in low-riskpatients: better treatment outcome

• 5-year EFS 88.7 ± 3% and OS 92.1 ± 2.6%.

1. Leukemia 2000;14:2205-22. 2. Leukemia 2010;24:265-84.3. Journal of clinical oncology 2012;30:1663-9.

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BFM 86, SR

Once or twice?

• double reinduction therapy had better EFS than single reinduction therapy

CCG-1891 study (1990-93)

<10-year-old, Intermediate risk

UKALL X trial (1985-90)

1. Lancet 1995;345:143-8.2. Blood 2002;99:825-33.

NoEarlyLate Both

x II⇧ Vin + pred in M

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Method

• 2002 - 2012

• All newly diagnosed ALL children

• TPOG-ALL-2002 protocol

• SR patients• SRA: double (x II) reinduction

• SRB: single (x I) reinduction

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Results

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TPOG ALL 2002 protocol

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Baseline CharacteristicsTrial

overallStandard risk Randomization

pvalue

(n=1,366)Total

(n=514)

Eligible for randomization

(n=387)

Eligible but not randomization

(n=127)

SRA (n=191)

SRB (n=196)

Sex

Male 59% 56% 59% 48% 64% 54% 0.032

Female 41% 44% 41% 52% 36% 46%Age (years)

Median (IQR)

5.1 (3.1-10.1)

4 (3-5.3)

4 (3-5.4)

3.9 (3-5.1)

4 (2.8-5.3)

4.1 (3.1-5.6)

0.347

<5 49% 70.6% 69.8% 73% 71% 68.4% 0.5325-10 26% 29.2% 27.9% 27% 29% 31.1%

>=10 25% 0.2% 0.3% 0 0 0.5%

WBC (x10^9 per L)Median (IQR)

1.6 (4.9-59)

6.4 (3.6-14.4)

5.9 (3.4-14.2)

8.5 (4.2-18.3)

5.7(3.4-14.7)

6.3 (3.2-11.9)

0.961

<10 40% 65% 68.2% 55.9% 66% 70.4% 0.441

10-19 14% 16% 13.7% 22.8% 14% 13.3%20-49 18% 17% 16.8% 18.9% 19.5% 14.3%

50-99 11% 1% 1% 0.8% 0.5% 1.5%

>100 17% 1% 0.3% 1.6% 0 0.5% 8

SRA (x II) vs SRB (x I)

xII 5-year: 93.7 ± 1.8%xI 5-year: 91.6 ± 2.1% xII 5-year: 89.8 ± 2.3%xI 5-year: 85.2 ± 2.7%

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Discussion

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BFM 2002 (2002-07)

SR

7 weeks

4 weeks 4 weeks

Protocol Prot II (7 wks) Prot III (4 wks) x 2

Dexamethasone 10mg/m2

Day 1-2110mg/m2

Day 1-14Vincristine 1.5mg/m2

Day 8, 15, 22, 291.5mg/m2

Day 1, 8Doxorubicin 30mg/m2

Day 8, 15, 22, 2930mg/m2

Day 1, 8L-asparaginase 10,000units/m2

Day 8, 11, 15, 1810,000units/m2

Day 1, 4, 8, 11Cyclophosphamide 1,000mg/m2

Day 36500mg/m2

Day 15Cytarabine 75mg/m2

Day 38-41, 45-4875mg/m2

Day 17-20, 24-276-thioguanine 60mg/m2

Day 36-4960mg/m2

Day 15-28

J Clin Onc 2014;32:174-84. 11

J Clin Onc 2014;32:174-84. 12

UK ALL 2003 trial (2003-11)

MRD low-risk patients

• similar outcome by 1 or 2 courses of reinduction

Lancet Oncol 2013;14:199-209.13

Protocol TPOG ALL 2002 BFM 86,90,951 IC-BFM 20022 St Jude XIIIB3 UK ALL 20034

DurationSRB: 3weeksSRA: 6weeks

Prot II: 7weeks Prot III: 4weeks x2

6weeks 7weeks or 14weeks

Dexamethasone8mg/m2

Day 1-8,15-2110mg/m2

Day 1-2110mg/m2

Day 1-14(Prednisone) 40mg/m2

Day 1-28

10mg/m2

Day 2-8,16-22

Vincristine1.5mg/m2

Day 1, 8, 151.5mg/m2

Day 8, 15, 22, 291.5mg/m2

Day 1, 81.5mg/m2

Day 1, 8, 15, 221.5mg/m2

Day 2, 9, 16

Doxorubicin(Epirubicin) 30mg/m2

Day 1

30mg/m2

Day 8, 15, 22, 2930mg/m2

Day 1, 8(Daunorubicin) 25mg/m2

Day 1, 8

25mg/m2

Day 2, 9, 16

L-asparaginase5,000units/m2

Day 2, 4, 6, 8, 10, 12

10,000units/m2

Day 8, 11, 15, 1810,000units/m2

Day 1, 4, 8, 1110,000units/m2

Day 2, 4, 6, 8, 10, 12

(Pegylated) 1,000units/m2

Day 4

Cyclophosphamide1,000mg/m2

Day 36500mg/m2

Day 151,000mg/m2

Day 29

Cytarabine75mg/m2

Day 38-41, 45-4875mg/m2

Day 17-20, 24-27300mg/m2

Day 2275mg/m2

Day 30-33, 37-40

6-thioguanine60mg/m2

Day 36-4960mg/m2

Day 15-28(6-MP)75mg/m2

Day 29-42(6-MP) 60mg/m2

Day 29-42

Others(Etoposide)300mg/m2 Day 22(Methotrexate)2g/m2 Day 29, 36

1. Leukemia 2000;14:2205-22. 2. Leukemia 2010;24:265-84.3. Journal of clinical oncology 2012;30:1663-9.4. Lancet Oncol 2013;14:199-209.

Conclusion

• Two courses of reinduction treatment have not shown to be more beneficial than one course for SR patients in TPOG-ALL-2002 study.

• MRD-based therapy applied in current TPOG-ALL-2013 protocol

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Acknowledgement

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