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  • Acute leukemia Lymphoma

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    2

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    1 . 2 .. 3 . 4 .. 5 . 6 ..

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    3

    (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

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    4

    National Protocol for Acute lymphoblastic leukemia (ALL) 5

    (diagnostic investigation) 5 ALL (Classification) 6

    Low risk ALL 7 High-risk ALL 10 CNS disease 12

    testicular involvement 12

    National Protocol for Acute non-lymphocytic leukemia (ANLL) 14 ANLL (Classification): 14 ANLL 14

    Appendix Guideline for Administration of High dose Methotrexate 34 Modified Toxicity Criteria for Cancer Chemotherapy 35 Chemotherapy Modification Guideline for Hepatic Dysfunction 36 Chemotherapy Modification Guideline for Renal Dysfunction 37 Anthracyclin Record Sheet 38 Guideline For Drug Preparation 39

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    5Thai 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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    63. 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) 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:

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    7 infant leukemia mature B-cell ALL high-risk ALL high-

    risk 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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    8 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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    9 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 & high-risk interim maintenance x 3 ( maintenance) delayed intenstification/ reinduction induction vincristine x 3 , doxorubicin 1 , dexamethasone prednisolone cyclophosphamide, AraC 6MP Maintenance Methotrexate 20 mg/M2 once weekly PO 6-mercaptopurine 50 mg/M2/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/re-induction Induction of remission 4-drug induction: Vincristine 1.5 mg/M2 IV weekly x 5 wks (days 1, 8, 15, 22, 29) Doxorubicin x 25 mg/M2 IV x 4 doses (days 1, 8, 15, 22) 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 day 35

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    11

    induction of remission 4-drug delayed recovery of neutrophil 6 vincristine remission 6 Consolidation & CNS prophylaxis Cyclophosphamide 1 g/M2 (day 1) followed by AraC 75 mg/M2 x 8 days (day2-5, 8-11) 6-mercaptopurine 50 mg/ M2 x14 days (days 1-15) Intrathecal methotrexate (dose ) x 2 doses 2 (during Cyclo-AraC) ANC>1,000 /ul, platelet count > 100,000/ul high-dose methotrexate 1.5 g/M2 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 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)

    high-risk ALL intensification/ re-induction 2 interim maintenance 3 cyclophosphamide, AraC 6MP 3 low-risk ALL total doxorubicin 6 2 low-risk A