แนวทางการรักษาโรคมะเร็งในเด็ก-2557 (1)

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Supportive care guidelineAntiemetics Corticosteriods should not be used as antiemetics or to prevent infusional toxicity of amphoteracin B.Mucosal evaluation and care Mucositis is expected to be severe, liberal use of pain medication is encouraged. Dental evaluation beforetherapy is recommended.Suppression of menstruation Menstruating females may receive depo-provera during the entire course of therapy. Supression of menseshould be continued until platelet is 50,000 without transfusion support.Infection prophylaxisPneumocystis prophylaxis PCP prophylaxis should be start as soon as possible after diagnosis of AML and continue until 6 monthsafter all therapy is completed.  First line: Trimethoprin-sulfamethoxazole at 150/750 mg/m2/day (Max: 320 mg/day of trimethoprim) in2 divided doses on 3 consecutive days per week  Second line options: Dapsone 2 mg/kg/day (Max: 100 mg/day) or aerosolized pentamidine 300 mginhaled monthly or intravenous pentamidine 4 mg/kg/dose every 4 weeksPrevention of viral infection Uses of leukoreduced blood product are strongly encouraged. Prophylactic acyclovir can reduce recurrence of mucocutaneous HSV infection.Prevention of bacteria and invasive fungal infection Infection related mortality continues to be high during induction and consolidation. Follow institutionalpolicy for antimicrobial prophylaxis such as ciprofloxacin plus fluconazole (voriconazole, itraconazole orposaconazole) during neutropenic phase after each chemotherapy cycle.Acute Myeloid Leukemia (AML): Supportive care guideline 87

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Off therapy follow up guidelineEnd of therapy evaluation:  Bone marrow aspiration, clot section or biopsy  Echo or MUGA and EKG  UA  Electrolyte, calcium, magnesium, phosphate, BUN, Cr  LFT1st year off therapy:  Follow up Q 1 month for the first 6 months then Q 2 months for month 6-12 with CBC c diff  Discontinue PCP prophylaxis at 6 months off therapy  Echo or MUGA/ EKG at the end of therapy and month 7 then as indicated  AST/ALT Q 2 months until normal  BUN/Cr, BMA and LP as clinically indicated2nd year off therapy:  Follow up Q 4 months with CBC c diff3rd year off therapy:  Follow up Q 6 months with CBC c diff4th year off therapy and afterward  Follow up annually with CBC c diff  Follow long term survivor guidelineAge at diagnosis XRT Anthracycline dose (mg/m2) ECHO(MUGA)/EKG interval (years)1-4 y/o Yes < 300 1 >= 300 1 No < 100 5 100-299 2>= 5 y/o Yes >= 300 1 No < 300 2 >= 300 1 < 200 5 200-299 2 >=300 1Acute Myeloid Leukemia (AML): Off therapy follow up guideline 88

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 1301]Protocol name: Thai-POG AML 1301Reference: COG AAML 1031Protocol for: Low Risk AML Total Pages: 5Open date: Jauary 2014Patient eligibility:Acute Myeloid Leukemia with Presence of low risk molecular marker: Inv 16, t(8,21) regardless of Monosomy 5, 7, -5q, MLL-generearrangement or MRD status at the end of induction Normal cytogenetic with MRD < 0.1% at the end of induction-I AML patients with no molecular marker and cytogenetic information available.Patient’s name Age SexHospital HN BW kg Ht cm BSA m2Disease Status: Treatment schema:Initial WBC: Induction-IFAB Morpholgy (M0-M7):Immuno-phenotype: End of Induction evalCNS status (circle one): Positive NegativeIsolated Myeloid sarcoma (circle one): Yes No High Risk featuresIf yes, describe:Cytogenetics: FISH: No Yes LR-Induction-II HR protocolMutation Status: FLT3 NPM1 CEBP-AEnd of Induction evaluation:BMA (circle): M1 M2 M3 LR-Consolidation-IMRD (circle): Negative PositiveImaging: LR-Consolidation-IIPost induction risk assignment (check one):  Low Risk High Risk: due toEnd of therapy date: / / 89Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML1301]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase I: INDUCTION-I (5 weeks) Date start:Week 1 2 34 5Day 1 8 15 22 28 29 Date due Date givenMedication: Start next courseARA-C _______ mg Q 12 H IV CCCCCCC CCC (Induction-IDA mg IV I II II) on day (T) (T) 29 or whenIT-ARA-C mg T (T) + (T) (T) blood count + + (+) + + parametersInvestigation: + (+) + + + are metCBC/diff + + (+) +CSF cell count/ cytospin + +BUN, Cr, TB,DB, AST, ALT + +BM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional)Drug Route Dosage DaysCytarabine (ARA-C IV) IV over 30 minutes 100 mg/m2/dose Q 12 hours or Days 1-10 3.3 mg/kg/dose Q 12 hours if BSA < 0.6 m2IDArubicin (IDA) IV drip in 4 hours 12 mg/m2/dose once a day or Days 1,3,5 0.4 mg/kg/dose once a day if BSA < 0.6 m2Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0.-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote  For CNS 3 patient: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatment. Patient with refractory CNS leukemia following 6 dose of therapy will be manage according to institutional protocol  For low risk patient: No need for HLA-typing  !!! For patient with no molecular or cytogenetics information available who treat according to LR-AML protocol: If patient have available sibling(s), send HLA-typing from patient and all siblings as soon as ANC > 500 and no visible peripheral blasts to find possible match related donor to do HSCT after Consolidation-IEnd of induction evaluation and post induction risk assignment for AML: Low Risk High Risk Presence of low risk molecular marker: Inv 16,  FLT3/ITD + with high allelic ration > 0.4 regardlesst(8,21) regardless of Monosomy 5, 7, -5q or MRD of low risk featurestatus at the end of induction Presence of monosomy 5, 7, -5q without low risk Normal cytogenetic with MRD < 0.1% at the end of molecular markerinduction-I  Normal cytogenetic with MRD >= 0.1% at the end of Induction-I Induction failure (M2, M3 at the end of Induction)Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 901301]

Patient’s name Thai Pediatric Oncology Group SexHospital ชมรมโรคมะเร็งเด็ก kg Ht cm BSA m2 Age HN BWPhase II: LR-INDUCTION- II (4 weeks) Date start:Begin on Day 29 of Induction-I. It is suggested but not required to have ANC > 1,000 cells/µl and Platelets> 75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due C (T) (T) (T) Start next (T) + + course Date given (Consolidation-I) + (+) + (+) on day 29 orMedication: + + + when blood + countARA-C mg Q 12 H IV CCCCCCC parameters are metIDA mg IV I I IIT-ARA-C mg T (T)Investigation:CBC/diff +CSF cell count/ cytospin + (+)BUN, Cr, TB,DB, AST, ALT +BM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional) +Drug Route Dosage DaysCytarabine (ARA-C IV) IV over 30 minutes 100 mg/m2/dose Q 12 hours or 3.3 mg/kg/dose Q 12 hours if BSA < 0.6 m2 Days 1-8IDArubicin (IDA) IV drip in 4 hours 12 mg/m2/dose once a day or Days 1,3,5 0.4 mg/kg/dose once a day if BSA < 0.6 m2Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote For patient with CNS negative at diagnosis but develop CNS disease at the beginning of induction-II: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatments. Patient with refractory CNS leukemia following 6 dose of therapy will be manage according to institutional protocolAcute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 911301]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex BW kg HtHospital HN Date start: cm BSA m2Phase III: LR- CONSOLIDATION -I (4 weeks)Begin on Day 29 of Induction-II. It is suggested but not required to have ANC > 1,000 cells/µl and Platelets> 75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due Date givenMedication: Start next courseARA-C mg Q 12 H IV CCCCC (Consolidation-ETOP mg IV E EE EEIT-ARA-C mg T II) on day 29 orInvestigation: + + + + when blood ++ + + + countCBC/diffCSF cell count/ cytospin parameters areBUN, Cr, TB,DB, AST, ALT metBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional) + +CrCl if Cr> 2 mg/dl or 2 xULNDrug Route Dosage DaysCytarabine IV over 1-3 hours 1,000 mg/m2/dose Q 12 hours or(HD ARAC) 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2 Days 1-5Etoposide (ETOP) IV over 60 -120 minutes 150 mg/m2/dose once a day or Days 1-5 5 mg/kg/dose once a day if BSA < 0.6 m2Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote For patient with CNS negative at diagnosis but develop CNS disease at the beginning of consolidation-I is considered CNS relapse. Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose. For patient with no molecular or cytogenetics information available who treat according to LR-AML protocol with available matched related donor: o Consider HSCT after consolidation-IAcute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 921301]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex kg HtHospital HN BW Date start: cm BSA m2Phase IV: LR- CONSOLIDATION - II (4 weeks)Begin on Day 29 of Consolidation-I. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets>75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29Date dueDate givenMedication:ARA-C _______ mg Q 12 H IV CCCCMITOX _______ mg IV MMMMIT-ARA-C _______ mg TInvestigation: End of therapyCBC/diff + + + + evaluation.CSF cell count/ cytospin +BUN, Cr, TB,DB, AST, ALT + + + +BM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional) +CrCl if Cr> 2 mg/dl or 2 xULN +Drug Route Dosage Days 1,000 mg/m2/dose Q 12 hours orCytarabine IV over 1-3 hours 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2 Days 1-4(HD ARAC) 12 mg/m2/dose once a day orMitoXANTRONE IV over 15-30 minutes 0.4 mg/kg/dose once a day if BSA < 0.6 m2 Days 3-6(MITOX)Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote  Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose.  End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, E’lyte, CA, Phos, BUN, Cr, AST/ALT, TB/DB.Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 931301]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 1302]Protocol name: Thai-POG AML 1302Reference: COG AAML 1031Protocol for: High Risk AML Total Pages: 5Open date: January 2014Patient eligibility:Acute Myeloid Leukemia with FLT3/ITD + with high allelic ratio > 0.4 regardless of low risk feature Presence of monosomy 5, 7, -5q or MLL rearrangement without low risk molecular marker Normal cytogenetic with MRD >= 0.1% at the end of Induction-I Induction failure (M2, M3 at the end of Induction-I)Patient’s name HN BW Age SexHospital kg Ht cm BSA m2Disease Status:Initial WBC: Morphology: FAB (M0-M7):CNS status (circle one): Positive Negative Immuno-phenotype:Isolated Myeloid sarcoma (circle one): Yes No Treatment schema:If yes, describe: Induction-ICytogenetics: FISH HR featuresMutation Status: FLT3 NPM1 CEBP-A HR-Induction-IIEnd of Induction evaluation:BMA (circle): M1 M2 M3 HR-Consolidation-I PositiveMRD (circle): Negative -Donor + DonorImaging: HR-Consolidation-II HSCTPost induction Management (check one): HSCT donor available: HSCT after HR-Consolidation I  Donor type: (circle one) MRD MUD MUCB MMRD Haplo HSCT donor not available: HR protocol chemotherapyEnd of therapy date: //Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 941302]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name HN BW Age SexHospital kg Ht cm BSA m2Phase I: INDUCTION - I (5 weeks) 2 Date start: 5Week 1 8 34 29Day 1 15 22 28 Date due Date givenMedication: CCCCCCC CCC (T) (T) + Start next I II (T) (T) + + + courseARA-C _______ mg Q 12 H IV T (T) + + + (Induction-II)IDA _______ mg IV + (+) + (+) + on day 29 orIT-ARA-C _______ mg + + + when blood + (+) countInvestigation: + parameters are metCBC/diff +CSF cell count/ cytospinBUN, Cr, TB,DB, AST, ALTBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional)Drug Route Dosage DaysCytarabine IV over 30 minutes 100 mg/m2/dose Q 12 hours or Days 1-10(ARA-C IV) 3.3 mg/kg/dose Q 12 hours if BSA < 0.6 m2IDArubicin (IDA) IV drip in 4 hours 12 mg/m2/dose once a day or Days 1,3,5 0.4 mg/kg/dose once a day if BSA < 0.6 m2Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote For CNS 3 patient: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatment.Patient with refractory CNS leukemia following 6 dose of therapy will be manage according toinstitutional protocol In all High risk patients: HLA typing should be done from the patient and all available siblings assoon as patient’s ANC > 500 and no evidence of peripheral blast. Activate donor search as soon aspossible in patient who have no match related donor to find any available donor for HSCT afterconsolidation-IEnd of induction evaluation and post induction risk assignment for AML: Low Risk High Risk  Presence of low risk molecular marker: Inv 16,  FLT3/ITD + with high allelic ration > 0.4t(8,21) regardless of Monosomy 5, 7, -5q or MRD regardless of low risk featurestatus at the end of induction  Presence of monosomy 5, 7, -5q without low risk  Normal cytogenetic with MRD < 0.1% at the end molecular markerof induction-I  Normal cytogenetic with MRD >= 0.1% at the end of Induction-I  Induction failure (M2, M3 at the end of Induction)Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 951302]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age Sex kg Ht cm BSA m2Hospital HN BW Date start:Phase II: HR-INDUCTION - II (4 weeks)Begin on Day 29 of Induction-I. It is suggested but not required to have ANC > 1,000 cells/µl and Platelets> 75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due Start next course (Consolidation-I) Date given on day 29 orMedication: when blood count parametersARA-C _______ mg Q 12 H IV CCCC are metMITOX _______ mg IV MMMMIT-ARA-C _______ mg T (T) (T) (T) (T) (T)Investigation:CBC/diffCSF cell count/ cytospinBUN, Cr, TB,DB, AST, ALTBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG optional) Drug Route Dosage DaysCytarabine IV over 30 minutes 1,000 mg/m2/dose Q 12 hours or Days 1-4(ARA-C IV) 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2Mitoxantrone (MITOX) IV drip over 15-30 12 mg/m2/dose once a day or 0.4 mg/kg/dose once a day if BSA < 0.6 m2 Days 3-6 minutesIntrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote For patient with CNS negative at diagnosis but develop CNS disease at the beginning ofinduction-II: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatments. Patientwith refractory CNS leukemia following 6 dose of therapy will be manage according to institutionalprotocol Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose.Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 961302]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase III: HR- CONSOLIDATION - I (4 weeks) Date start:Begin on Day 29 of Induction-II. It is suggested but not required to have ANC > 1,000 cells/µl and Platelets> 75,000 cells/ µl.Week 1 2 345Day 1 8 15 22 29 Date due CCCCC + Start next Date given E EE EE + courseMedication: TARA-C _______ mg Q 12 H IV (Consolidation-ETOP _______ mg IV + II or HSCT) onIT-ARA-C _______ mg + day 29 or when +Investigation: blood count + + + parameters areCBC/diff + metCSF cell count/ cytospin ++BUN, Cr, TB,DB, AST, ALT +BM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional)CrCl if Cr> 2 mg/dl or 2 xULNDrug Route Dosage DaysCytarabine (HD ARAC) IV over 1-3 hours 1,000 mg/m2/dose Q 12 hours or Days 1-5 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2 IV over 60 -120 minutes 150 mg/m2/dose once a day orEtoposide (ETOP) 5 mg/kg/dose once a day if BSA < 0.6 m2 Days 1-5Intrathecal Cytarabine IT Age(yrs ) Dose Day 1(IT ARA-C) 0-0.99 20 mg 1-1.99 30 mg 2-2.99 50 mg ≥3 70 mgNote For patient with CNS negative at diagnosis but develop CNS disease at the beginning ofconsolidation-I is considered CNS relapse. Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose. Post Consolidation-I treatment assignment: o Any available HSCT donor: Proceed to HSCT o No available HSCT donor: Continue consolidation-IIAcute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 971302]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase IV: HR- CONSOLIDATION - II (4 weeks) Date start:Begin on Day 29 of Consolidation-I. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets>75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due Date givenMedication:ARA-C _______ mg Q 12 H IV CC CCL-ASP _______ IU IM AAInvestigation: End of therapy evaluation.CBC/diffCSF cell count/ cytospinBUN, Cr, TB,DB, AST, ALTBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional)CrCl if Cr> 2 mg/dl or 2 xULNDrug Route Dosage DaysCytarabine IV over 3 hours 3,000 mg/m2/dose Q 12 hours or Days 1,2 and 8,9(HD ARAC) 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2 6,000 IU/m2/dose once a day orL-Asparaginase IM 200 IU/kg/dose once a day if BSA < 0.6 m2 Days 2 and 9. To be(L-ASP) given 6 hours after the start of 4th and 8th dose of ARA-CNote Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose. End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, E’lyte, CA, Phos,BUN, Cr, AST/ALT, TB/DB.Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 981302]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Optional treatment protocol for acute myeloid leukemia [Thai-POG AML-02-08]Protocol name: TPOG AML-02-08 Total Pages: 8Protocol for: Optional protocol for new patient diagnosed with AMLOpen date: January 2014Patient eligibility:  De novo Acute Myeloid LeukemiaPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Disease Status:Initial WBC: Morphology: FAB (M0-M7):CNS status (circle one): Positive Negative Immuno-phenotype:Isolated Myeloid sarcoma (circle one): Yes No Treatment schema: If yes, describe: Induction-ICytogenetics: FISH +/-Induction-IIEnd of Induction evaluation:BMA (circle): M1 M2 M3 Consolidation-I Imaging: Consolidation-IIPost Induction Management (check one): - Donor + Donor  Match related HSCT donor available:  HSCT after Consolidation-II Consolidation-III HSCT  No Match related HSCT donor not available: Consolidation-IV Complete AML chemotherapyCNS treatment program: YES NODescribe:End of therapy date: / /Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 9902-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age Sex 3 cm BSAHospital HN BW 15 kg Ht m2 Date start: 5Phase I: INDUCTION (5 weeks) + 28 29 + 4Week 1 2 22Day 1 8 Date due Date givenMedication: Start nextARA-C _____ mg Q 24 H IV CCCCCCC course onIDA _______ mg IV III day 29 orTIT _______ mg T whenInvestigation: bloodCBC/diff + + + + countCSF cell count/ cytospin + + parametersBUN, Cr, TB,DB, AST, ALT +BM Aspiration + + + are metBiopsy and MRD (optional) +ECHOor MUGA and EKG (optional) +Drug Route Dosage DaysCytarabine (ARA-C IV) IV over 24 hours 100 mg/m2/dose Q 24 hours or Days 1-7 3.3 mg/kg/dose Q 24 hours if BSA < 0.6 m2IDArubicin (IDA) IV drip in 4 hours 12 mg/m2/dose once a day or Days 1-3 0.4 mg/kg/dose once a day if BSA < 0.6 m2Intrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1 0-0.99 6 mg 15mg 6mg 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mgNote For CNS disease patient: at diagnosis or during treatment, CNS therapy program will be started at the end of consolidation IV. It will include brain radiation 1800 rad and spinal radiation 1,200 rad. If patient have available sibling(s), send HLA-typing from patient and all siblings as soon as ANC > 500 and no visible peripheral blasts to find possible match related donorEnd of induction treatment assignment for AML:BM aspiration on day 28:  M1 start Consolidation-I  M2-M3  start Induction-IIAcute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10002-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex kg Ht cm BSA m2Hospital HN BW Date start: 5Phase I/II: INDUCTION-II (4 weeks) 34 29 15 22Begin on Day 29 of Induction-I regardless of blood count Start next course ++ (Consolidation-I)Week 1 2 ++Day 1 8 on day 29 or when blood Date due count parameters Date given are metMedication: + +ARA-C _______ mg Q 24 H IV CCCCCCCIDA _______ mg IV IIITIT _______ mg TInvestigation: + + + +CBC/diff +CSF cell count/ cytospinBUN, Cr, TB,DB, AST, ALTBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional +Drug Route Dosage DaysCytarabine (ARA-C IV) IV over 24 hours 100 mg/m2/dose Q 24 hours or Days 1-7 3.3 mg/kg/dose Q 24 hours if BSA < 0.6 m2 IV drip in 4 hours 12 mg/m2/dose once a day orIDArubicin (IDA) 0.4 mg/kg/dose once a day if BSA < 0.6 m2 Days 1-3Intrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1 0-0.99 6 mg 15mg 6mg 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mgNote BM evaluation on day 28 o M-1: start next course of therapy (Consolidation-I) on day 29 or when blood count parameter are met o M-2, M-3: off protocol. Consider salvage therapy.Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10102-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase II: CONSOLIDATION-I (4 weeks) Date start:Begin on Day 29 of Induction-I or II. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets > 75,000 cells/ µl.Week 1 2 345Day 1 8 15 22 29 Date due + + Date givenMedication:ARA-C _______ mg Q 12 H IV CCC Start next courseETOP mg IV EEEE (Consolidation-II)TIT mg T on day 29 orInvestigation: when blood countCBC/diff + ++ parameters areCSF cell count/ cytospin + metBUN, Cr, TB,DB, AST, ALT + ++BM Aspiration +Biopsy and MRD (optional) +ECHOor MUGA and EKG (optional)CrCl if Cr> 2 mg/dl or 2 xULNDrug Route Dosage DaysCytarabine (HD ARAC) IV over 1-3 hours 3,000 mg/m2/dose Q 12 hours or Days 1-3Etoposide (ETOP) IV over 60 -120 minutes 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2 125 mg/m2/dose once a day or 5 mg/kg/dose once a day if BSA < 0.6 m2 Days 2-5Intrathecal Therapy IT Age(yrs) MTX Ara-C HC Day 1 0-0.99 6 mg 15mg 6mg 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mgNote For patient with CNS negative at diagnosis but develop CNS disease at the beginning ofconsolidation-I is considered CNS relapse. Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose.Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10202-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase III: CONSOLIDATION-II (4 weeks) Date start:Begin on Day 29 of Consolidation-I. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets>75,000 cells/ µl.Week 12345Day 1 8 15 22 29Date dueDate givenMedication: CC Start nextARA-C _______ mg Q 12 H IV CC courseL-ASP _______ IU IM AA (Consolidation-TIT_______ mg T III or HSCT) onInvestigation: + + + + day 29 or when + + + + blood countCBC/diff + parameters areCSF cell count/ cytospinBUN, Cr, TB,DB, AST, ALT metBM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional) +CrCl if Cr> 2 mg/dl or 2 xULN +Drug Route Dosage DaysCytarabine IV over 3 hours 3,000 mg/m2/dose Q 12 hours or Days 1,2 and 8,9(HD ARAC) IM 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2 Days 2 and 9. ToL-Asparaginase 6,000 IU/m2/dose once a day or be given 6 hours(L-ASP) IT 200 IU/kg/dose once a day if BSA < 0.6 m2 after the start ofIntrathecal Therapy 4th and 8th doseNote Age(yrs ) MTX Ara-C HC of ARA-C 0-0.99 6 mg 15mg 6mg Day 1 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mg Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose ofHD-ARAC and continuing for 24 hours after the last dose. End of consolidation-II treatment assignment: o Available match related donor  HSCT o No available match related donor  continue consolidation-IIIAcute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10302-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase IV: CONSOLIDATION-III (4 weeks) Date start:Begin on Day 29 of Consolidation-II. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets > 75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due Date givenMedication:ARA-C _______ mg Q 12 H IV CCCETOP _______ mg IV EEEE Start next courseTIT _______ mg T (Consolidation-IV) on day 29 or whenInvestigation:CBC/diff +++ + blood countCSF cell count/ cytospin + parameters are metBUN, Cr, TB,DB, AST, ALT + + + +BM AspirationBiopsy and MRD (optional)ECHOor MUGA and EKG (optional) +CrCl if Cr> 2 mg/dl or 2 xULN +Drug Route Dosage Days 3,000 mg/m2/dose Q 12 hours orCytarabine IV over 1-3 hours 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2 Days 1-3(HD ARAC) IV over 60 -120 minutes 125 mg/m2/dose once a day orEtoposide 5 mg/kg/dose once a day if BSA < 0.6 m2 Days 2-5(ETOP)Intrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1 0-0.99 6 mg 15mg 6mg 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mgNote Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose.Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10402-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase V: CONSOLIDATION-IV (4 weeks) Date start:Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets>75,000 cells/ µl.Week 1 2 3 4 5Day 1 8 15 22 29 Date due Date givenMedication:ARA-C _______ mg Q 12 H IV CC CC + + End of therapyL-ASP _______ IU IM A A + + evaluation orTIT _______ mg CNS treatment T + program for CNSInvestigation: + disease patient +CBC/diff +CSF cell count/ cytospin +BUN, Cr, TB,DB, AST, ALTBM Aspiration +Biopsy and MRD (optional) +ECHOor MUGA and EKG (optional)CrCl if Cr> 2 mg/dl or 2 xULNDrug Route Dosage DaysCytarabine IV over 3 hours 3,000 mg/m2/dose Q 12 hours or Days 1,2 and 8,9(HD ARAC) 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2L-Asparaginase IM 6,000IU/m2/dose once a day or Days 2 and 9. To(L-ASP) 200 IU/kg/dose once a day if BSA < 0.6 m2 be given 6 hours after the start of 4th and 8th dose of ARA-CIntrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1 0-0.99 6 mg 15mg 6mg 1-1.99 8 mg 20mg 8mg 2-2.99 10 mg 30mg 10mg ≥3 12 mg 50mg 12mgNote Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose. End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, E’lyte, CA, Phos,BUN, Cr, AST/ALT, TB/DB.Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10502-08]

Patient’s name Thai Pediatric Oncology Group Age SexHospital ชมรมโรคมะเร็งเดก็ kg Ht cm BSA m2 HN BWPhase VI: CNS- Treatment program (for CNS disease patient only) Date start:Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/µl andPlatelets>75,000 cells/ µl.Radiation field :( )Total radiation dose : ( )Number of fractions : ( )Date start :( )Last day of radiation : ( )CT date :( )Note End of therapy evaluation should be done 8 weeks after complete radiation therapy: CBC, MMURGI bAr/aEinCHfoOr,inBtMraAc/rcalnoitaslecchtoiolrnoomrabpioaptiseyn,t.UA, E’lyte, CA, Phos, BUN, Cr, AST/ALT, TB/DB, CT orAcute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 10602-08]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 0106]Protocol name: Thai-POG APL 0106Reference: PETHEMA LPA-99 studyProtocol for: Acute Promyelocytic Leukemia Total Pages: 5Patient eligibility: Acute Myeloid Leukemia with o PML/RARa fusion gene from PCR, FISH or cytogeneticPatient’s name HN Age SexHospital BW kg Ht cm BSA m2Disease Status: Treatment schema:Initial WBC: FAB Morpholgy (M0-M7): InductionImmuno-phenotype: Negative N Day#45 evaluationCNS status (circle one): PositiveIsolated Myeloid sarcoma (circle one): Yes No If yes, describe: RemissionCytogenetics: FISH: No YesEnd of Induction evaluation:Day 45 BMA (circle): M1 M2 M3 ATRA; Max 90Imaging: days Consolidation#1Duration of ATRA days Yes Consolidation#2Remission status from day 45-90: RemissionPost Consolidation treatment assigment (check one): No PML/RARa fusion PML/RARa negative  Maintenance: date No Maintenance Yes PML/RARa positive  Salvage therapy: datePost Salvage therapy No Salvage Rx PML/RARa negative  Maintenance: date PML/RARa positive  Off protocol Off protocol Yes PML/RARa fusionEnd of therapy date: / /Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 1070106]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase I: INDUCTION- (6-13 weeks) Date start:Week 1 2 3 4 5 6 7 8 1 15 36 45 9 10 11 12Day 57 78 90Date due Start nextDate given courseMedication: (consolidation)ATRA _______ mg Q 12 H PO on day 46 orIDA _______ mg IV III when BM show +Investigation: + remission or +CBC/diff + + + ++ + when bloodBUN, Cr, TB,DB, AST, ALT + + + ++ + countBM Aspiration + +Biopsy and MRD (optional) + + parameters areECHOor MUGA and EKG (optional) + metDrug Route Dosage DaysAll-Trans-Retinoic-Acid (ATRA) PO 25 mg/m2/day BID Days 1-Remission IV drip in 4 hours 10 mg/m2/dose once a day Days 1,2,3IDArubicin (IDA)Note  Continue ATRA until morphologic remission, maximum duration of 90days  Bone marrow aspiration on day 45 o In remission  start consolidation therapy o Not in remission  continue ATRA and repeat BMA periodically until remission (no more than 90 days) then start consolidation after remission o If patient is not in remission after 90days, consider switch to protocol which contain Arsenic.  Keep fibrinogen > 150 mg/dl and platelet count > 30,000-50,000/mm3 if patients develop sign of coagulopathy  Please see APL differentiating syndrome (ATRA syndrome) criteria for diagnosis and management guideline in Thai-POG AML management guidelineAcute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 1080106]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase II: Consolidation- (8 weeks) Date start:Begin on Day 46 of Induction or when in remission. It is suggested but not required to have ANC > 1,000cells/µl and Platelets > 75,000 cells/ µl.Week 1 2 3 3 4 5Day 1 8 15 16 22 29Date due Cycle 1 /Cycle 2 Start consolidationDate given /Medication: cycle 2 on day 29 IIIATRA _______ mg Q 12 H PO + of consolidation +IDA _______ mg IV + cycle 1.Investigation: Start Next courseCBC/diff (Salvage therapyBUN, Cr, TB,DB, AST, ALTBM Aspiration + + + or maintenance)Biopsy and MRD (optional) + on day 29 ofECHOor MUGA and EKG (optional) consolidation cycle 2Drug Route Dosage DaysAll-Trans-Retinoic-Acid PO 25 mg/m2/day BID Days 1-15(ATRA) IV drip in 4 hours 10 mg/m2/dose once a day Days 1-3IDArubicin (IDA)Note Consolidation therapy consisted of 2 cycle. Each cycle should be given every 4 weeks Evaluate PML/RARa fusion gene after the end of Consolidation cycle#2 o PML-RARa negative  start maintenance phase o PML-RARa positive  Start Salvage therapy Cycle#1 date start / / Cycle#2 date start / / Post consolidation PML/RARa fusion gene (circle one): Positive NegativeAcute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 1090106]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase III: Salvage Therapy- (4 weeks) Date start:Begin after Day 29 of Consolidation cycle#2. It is suggested but not required to have ANC > 1,000 cells/µland Platelets > 75,000 cells/ µl.Week 1 2 345Day 1 8 15 22 29 Date due + + Date givenMedication: Start nextARA-C _______ mg Q 12 H IV CCC courseInvestigation: Maintenance onCBC/diff + + + day 29 or whenBUN, Cr, TB,DB, AST, ALT + ++ blood countBM Aspiration parameters areBiopsy and MRD (optional) metECHOor MUGA and EKG (optional) +CrCl if Cr> 2 mg/dl or 2 xULN +Drug Route Dosage DaysCytarabine (HD ARAC) IV over 1-3 hours 3,000 mg/m2/dose Q 12 hours or Days 1-3 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2Note Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HD-ARAC and continuing for 24 hours after the last dose. Salvage therapy is given only in patient whose PML/RARa fusion gene still positive after the end of consolidation phase Evalaute PML/RARa fusion gene after complete salvage therapy o PML/RARa negative  start maintenance phase o PML/RARa positive  off protocol. Consider other salvage regimen.Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 1100106]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase IV: Maintenance- (12 weeks) Date start:Begin on Day 29 of Consolidation cycle#2 or Salvage therapy. It is suggested but not required to have ANCW>Da1ey,e0k00 cells/µl and Plate11lets>2875,0001c53ells13/ 6µl. R24e2peat52m9 ain63te6nan47c3e the85r0apy 95fo7r to16ta04l of 71811cycl71e82. 8135Medication:ATRA______ mg po BID Repeat6-MP _____ mg PO daily next cycle M M M MMMMMMMMM for total ofIMnTvXes_t_i_g_a_t_i_onm:g PO + ++ 8 cycles +CBC/diffBUN, Cr, TB,DB, AST, ALT Drug Route Dosage DaysAll-Trans-Retinoic-Acid (ATRA) PO 25 mg/m2/day BID Days 1-156-Mercaptopurine (6-MP) PO 50 mg/m2/dose Day 1-84MNoettehotreaxate (MTX) PO 20 mg/m2/dose Day 1 then weekly until Day 78  6-MP and MTX should be hold when ANC < 500 or Plt < 50,0000.  6-MP and MTX should be restarted when ANC > 750 and Plt > 75,000  First time discontinuation: restart at full dose  Second time discontinuation and after: restart at 50% dose reduction. Slowly escalate dose by 25% in 2-4 week interval until reach original dose if ANC > 750 and Plt > 75,000  Recommend BM evaluation and TPMT gene mutation evaluation for oatient with prolong cytopenia more than 4 weeksCycle Date BSA Medication dosage Note: given 1 Weight ______ kg ATRA ________ mg po BID Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID2 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID3 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID4 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID5 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID6 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID7 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weekly Weight ______ kg ATRA ________ mg po BID8 Height ______ cm 6-MP _________ mg po daily BSA _______ m2 MTX ________ mg po weeklyAcute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 1110106]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กLymphoma Hodgkin diseaseRisk stratificationLow risk (LR) Intermediate Risk (IR) High Risk (HR)Stage I-A with no bulk Stage I-E, I-B and I-A with bulk Stage III-BStage II-A with no bulk Stage II-E, II-B and II-A with bulk Stage IV-B Stage III-A Stage IV-ADefinition:Stage groupingStage I Involvement of single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE)Stage II Involvement of 2 or more lymph node regions on the same side of diaphragm (II) or localizedcontiguous involvement of a single extralymphatic organ or site and its regional lymph nodes(s) withinvolvement of 1 or more lymph node regions on the same side of the diaphragm (IIE).Stage III Involvement of lymph node regions on both sides of the diaphragm (III), which may alsoaccompanied by localized contiguous involvement of an extralymphatic organ or site (IIIE), by involvement ofthe spleen (IIIS) or both (IIIE+S).Stage V Disseminated involvement of 1 or more extralymphatic organs or tissues, with or withoutassociated lymph node involvement, or isolated extralymphatic organ involvement with distant nodalinvolvementSymptoms and presentation“A” Symptoms: lack of “B” symptoms.“B” Symptoms: At least one of the following:Unexplained weight loss > 10% in the preceding 6 months;Unexplained recurrent fever > 38 C in the preceding months;Recurrent drenching night sweats in the preceding monthBulk diseaseLarge mediastinal mass: Tumor diameter > 1/3 of thoracic diameter on upright PA CXR.Large extra-mediastinal nodal aggregate: A continuous aggregate of nodal tissue that measures > 6 cmin the longest transverse diameter in the axial plane in any nodal area.Macroscopic splenic nodules: focal defect in the spleen seen on CT, PET or MRI imaging studiesconsistent with Hodgkin lymphoma will be deemed to be bulk diseaseLymphoma: Hodgkin disease 112

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กNumber of regions of nodal involvementEach of these 20 regions is counted separately for purpose of determining clinical group.Peripheral regions Central regions Lower regions Rt neck; cervical,  Waldeyer’s ring (include  Rt iliacsupraclavicular, occipital, pre- base of tongue)  Lt iliac auricular  Mediastinum (include  Rt inguinal and femoral Lt neck; cervical, paratracheal)  Lt inguinal and femoral  Rt popliteal supraclavicular, occipital, pre-  Hilar auricular  Mesenteric  Lt popliteal Rt infraclavicular Lt infraclavicular  Paraaortic (include retrocrural, portal and celiac) Rt axilla and pectoral  Splenic/splenic hilar Lt axilla and pectoral Rt epitrochlear and brachial Lt epitrochlear and brachialLymphoma: Hodgkin disease 113

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Clinical criteria for nodal involvementUpper torso Any node with longest transverse diameter > 1.5 cm Cervical or axillary node may reach >= 2 cm in the longest diameter on physical exam, USG, CT or MRI before being considered if reactive hyperplasia is considered possible Any cluster of matted or adherent nodes Any enlarged supraclavicular nodes Any mediastinal adenopathy Any FDG-positive nodesLower torso Any node with longest transverse diameter > 1.5 cm Inguinal and mesenteric node may reach >= 2 cm in the longest diameter on physical exam, USG, CT or MRI before being considered if reactive hyperplasia is considered possible Any FDG-positive nodes, liver or spleen A spleen or liver that has focal defect on imagingResponse criteria Measurable lesions up to the maximum of 6 lesions in total will be measured as a target lesion at baseline and followed for response Lesion size is expressed as the product of perpendicular diameter (PPD) PPD is obtained by multiply the longest diameter of the lesion by maximal diameter perpendicular to thelongest diameter (multiply of the two longest diameter from imaging) PPD = surrogate measurement of are with dimension of cm2PET result CT result Ninovdoulvlaermsepnltenic RESPONSE CompleteNegative -Complete disappear of all target nodal mass or mass of any size Negative Response - At least 80% reduction in sum of PPD of up to 6 largest nodal mass including mediastinum and return to normal size with no Partial response residual mass greater than 2 cmNegative -Complete disappear of all target nodal mass or mass of any size Positive -At least 80% reduction in sum of PPD of up to 6 largest nodal mass including mediastinum and return to normal size with no residual mass greater than 2 cmPositive -Complete disappear of all target nodal mass or mass of any size Not applicable Partial Response - At least 80% reduction in sum of PPD of up to 6 largest nodalPositive mass including mediastinum and return to normal size with no Not applicable Partial ResponsePositive residual mass greater than 2 cm Not applicable Stable DiseasePositive Less than complete disappearance but greater than 50% reduction Not applicable Progressive in sum of PPD of up to 6 of largest nodal masses. Disease Less than 50% reduction or less than 50% increase in sum of PPD of up to 6 of largest nodal masses with no new lesions. Greater than 50% increase in PPD of any of the nodal masses or development of new measurable lesionLymphoma: Hodgkin disease 114

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment schema Hodgkin Disease Low risk Intermediate risk High risk ABVE x 2 cycle ABVE-PC x 2 cycle CT/PET/Gal CT/PET/Gal CR PR/SD PR/SD (SER) CR (RER)ABVE x 2 cycle ABVE x 2 cycle MIED x 2 cycle ABVE-PC x 2 cycle CT/PET/Gal CT/PET/Gal CT/PET/Gal CR IFRT ABVE-PC x 2 cycleFollow up CR PR/SD/PD CT/PET/Gal PD SD/PR/CR PD Salvage protocol PR IFRT Follow up CRNote CR = complete remission, PR= partial remission, SD = stable disease, PD = progressive disease ABVE = Doxorubicin + Bleomycin + Vincristine + Etoposide ABVE-PC = Doxorubicin + Bleomycin + Vincristine + Etoposide – Prednisolone + Cyclophosphamide MIED = High dose methotrexate + Etoposide + Ifosphamide + dexamethasone IFRT = Involved field irradiation therapy Gal: Gallium scan CT is a standard for re-evaluation imaging, PET and Gal are optional for re-evaluation imagingLymphoma: Treatment schema 115

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Dose modification guidelines for chemotherapy toxicityABVE and ABVE-PC regimen: o Hematologic Toxicity  Full dose of chemotherapy should begin on day 22 if ANC >= 750/ul (with patient off G-CSF for at least 2 days before next cycle) and platelets are >= 75,000/uL. If a patient has not recovered by day 21, check CBC twice weekly and begin chemotherapy as soon as hematologic recovery. o Hepatic toxicity  If bilirubin > 1.5 x ULN when chemotherapy is due to be given, hold chemotherapy and check bilirubin twice weekly until it is < 1.5 x ULN. o Hematuria  Microscopic hematuria  Transient microscopic hematuria (=< 2 abnormal UA on 2 separate days during cycle of chemotherapy): Do not modify cyclophosphamide dose. Increase hydration (3,500 -4,000 ml/m2/day) and use total daily MESNA dose equal to 60% of daily cyclophosphamide dose.  Persistent microscopic hematuria (> 2 abnormal UA during a cycle of therapy): Do not modify the cyclophosphamide dose. Increase hydration (3,500 -4,000 ml/m2/day) and use total daily MESNA dose equal to 100% of daily cyclophosphamide dose. o Gross hematuria  All episode of gross hematuria should be evaluated in conjunction with pediatric urology consultation.  Transient gross hematuria (only 1 episode which clear to less than gross hematuria): During or following a cycle of therapy, Hold cyclophosphamide until hematuria clears. When hematuria clears, restarted at 50% of previous cyclophosphamide dose. Use hydration 3,500-4,000 ml/m2/day and MESNA at 100% of cyclophosphamide dose as a continuous drip over 24 hours. The cyclophosphamide dose may be escalated back to 100%, if tolerated, and mesna give at 100% as continuous drip.  Persistent gross hematuria: after completion of a cycle of therapy, hold subsequent cyclophosphamide doses until the urine clears to less than gross hematuria. When hematuria clears, restarted at 50% of previous cyclophosphamide dose. Use hydration 3,500-4,000 ml/m2/day and MESNA at 100% of cyclophosphamide dose as a continuous drip over 24 hours. The cyclophosphamide dose may be escalated back to 100%, if tolerated, and mesna give at 100% as continuous drip.  For persistent or recurrent gross hematuria on the mesna continuous drip: Discontinue subsequence cyclophosphamide dose. o Pulmonary  If DLCO in any diffusion capacity test is < 50% of the initial value or predicted value or if both DLCO and FEV/FVC show rapid parallel decrease, obtain blood gases, discontinue further bleomycin.Lymphoma: Dose modification guidelines for chemotherapy toxicity 116

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็o Cardiac  If SF < 28% or EF < 50% on 2 study at least 1 week apart, the doxorubicin should be held  If patient develop sign and symptoms of congestive heart failure or prolong QTc which are not attribute to other causes such as sepsis or renal failure, hold doxorubicin and perform ECHO/MUGA and EKG prior to next planned dose.o Peripheral neurotoxicity  Vincristine should be held or reduced only for incapacitating peripheral neurotoxicity. Vincristine can be resumed when the symptoms have improved or completely resolved. If held, the subsequent dose will be given at 25% dose reduction (Max: 2.1 mg)o Hypersensitivity reaction to Etoposide  Discontinue Etoposide infusion if patient exhibit hypersensitivity reaction relate to infusion.  If additional dose of etoposide are scheduled to complete therapy  Consider Etoposide phosphate substitution with premedication. If Etoposide phosphate is not available, continue further therapy with Etoposide with lower rate of infusion.  Premedication: o Prednisone 1 mg/kg/dose o Diphenhydramine 1 mg/kg/dose (Max: 50 mg)o Hypersensitivity reaction to Bleomycin  Discontinue Bleomycin infusion if patient exhibit hypersensitivity reaction relate to infusion  If additional dose of Bleomycin are scheduled to complete therapy  Continue further therapy with Bleomycin with lower rate of infusion.  Premedication: o Prednisone 1 mg/kg/dose o Diphenhydramine 1 mg/kg/doseMIED regimen:MethotrexateToxicity Grade ActionMyelosuppression On day 1 of each cycle: Delayed until recovery ANC < 750 or Plt < 75,000Mucositis, Severe Grade 3 (painful Consider Leucovorin rescue adjustment: see MTXabdominal pain, erythema, edema or infusion guidelineDiarrhea ulcers requiring IV)-Grade 4 (severe ulceration, required parenteral nutrition or intubation) or diarrheaLymphoma: Dose modification guidelines for chemotherapy toxicity 117

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กToxicity Grade ActionRenal toxicity GFR < 70 ml/min/1.73m2 Delay until recoveryAbnormal LFTs Not MTX induced LFT elevated Delayed 1 week. Give if ALT < 10x ULN MTX induced (up to 3 High dose MTX can cause hyperbillirubinemia and weeks after MTX) transaminitis that last up to 2 weeks that will not be consider toxicity required discontinuation of the drug Bilirubin > 1.5x ULN Persistent hyperbillirubinemia for longer than 3 weeks will result in discontinuation of MTXIfosphamide/EtoposideToxicity Grade Action Delayed until recoveryMyelosuppression On day 1 of cycle: ANC < 750 Reduce ETOP by 50% or Plt < 75,000 Delay for 1 week. If renal function does not improve, discontinue IFOS, confirm GFR andMucositis Grade 4 (severe ulceration, consider substituting Cyclophosphamide and MESNA at 500 mg/m2 x 5 days require TPN or intubation) after previous cycle or repeated Grade 3 (painful erythema, edema or ulcer requiring IV)Renal toxicity- Serum Cr > 1.5 x baseline orGlomerular GFR < 70 ml/min/1.73 m2Renal toxicity- FR 10-50 ml/min/1.73 m2 Reduce ETOP by 25%Tubular GFR < 10 ml/min/1.73 m2 Reduce ETOP by 50% Grade 1 (asymptomatic) No change Grade 2 (mild, reversible, Consider reduction of IFOS by 20% manageable with oral replacement) Grade 3 (reversible but require No further IFOS. Consider substituting IV replacement) or 4 cyclophosphamide and MESNA at 500 mg/m2 (irreversible require continued x 5days replacement)Lymphoma: Dose modification guidelines for chemotherapy toxicity 118

Toxicity Thai Pediatric Oncology Group ActionHematuria ชมรมโรคมะเร็งเด็ก Give additional MESNA bolus of 600 mg/m2 Grade then continuous infusion at double dose Dipstick positive prior to IFOS Microscopic during IFOS >= 2 No further IFOS. If hematuria resolves episode (> 50 RBC/HPF) completely, IFOS with double dose MESNA could be consider with the next cycle or consider substituting cyclophosphamide and MESNA at 500 mg/m2 x 5days >= Grade 2 (intermittent gross Discontinue IFOS, continue double dose hematuria with no clot); MESNA and hydration for 24 hours after excludes other cause; double IFOS. For the next cycle consider cyclophosphamide and MESNA at 500 mg/m2 dose MESNA +/- increase hydration x 5daysNeurological Grade 2 (confusion or No change unless persistent or distressing.Toxicity- Confusion,alteration of level of disorientation or attention Then decrease IFOS by 20%. If persists,consciousness deficit or somnolence or sedate reduce by a further 20%. interfering function but not daily living) Grade 3 (confusion or delirium Stop IFOS for this cycle. Decrease IFOS by or obtundation or stupor; 20% during next cycle. If persists, reduce by difficult to arouse, interfering a further 20%. with daily living)Neurological Grade 4 (harmful to others or Stop IFOS for this cycle and no further IFOS.Toxicity- Seizure self, require hospitalization or Give methylene blue at 2 mg/kg (Max: 50 coma) mg). The dose can be repeated at 4 hours and 8 hours after. Hypersensitivity, renal Grade 2 (self-limited and impairment and G-6PD deficiency are consciousness is preserved) contraindications for methylene blue. Substituting IFOS with cyclophosphamide and MESNA at 500 mg/m2 x 5days for next cycle. Stop IFOS for this cycle. Continue future cycle at the same dose. Grade 3 (consciousness is Stop IFOS for this cycle. Continue future altered) cycle at the same dose with anticonvulsant coverage.Lymphoma: Dose modification guidelines for chemotherapy toxicity 119

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กToxicity Grade Action Grade 4 (prolong, repetitive or Stop IFOS for this cycle and no further IFOS. difficult to control) Give methylene blue at 2 mg/kg (Max: 50 mg). The dose can be repeated at 4 hours and 8 hours after. Hypersensitivity, renal impairment and G-6PD deficiency are contraindications for methylene blue. Substituting IFOS with cyclophosphamide and MESNA at 500 mg/m2 x 5days for next cycle.Neurological >= Grade 2 (objective Omit further IFOS. For the next cycleToxicity-peripheral weakness or sensory loss or consider cyclophosphamide and MESNA at paresthesia but not interfere 500 mg/m2 x 5days.neuropathy with daily living)DexamethasoneHypertension: Doses should not be reduced. Sodium restriction and anti-hypertensive should be employed.Avoid calcium channel blockers due to prohemorrhagic effect.Hyperglycemia: Dose should not be reduced for hyperglycemia. Insulin therapy should be employed tocontrol blood sugar.Pancreatitis: Discontinue steroid in a presence of severe or hemorrhagic pancreatitis.Osteonecrosis: Do not modify steroid therapy during treatment.Varicella: Steroids should be held during active infection except during induction.Inability to use oral doses: Dexamethasone: substitute the IV preparation mg for mg Prednisone: Substitute IV methylprednisone at 80% of oral prednisone dose. o Severe infection: Do not hold or discontinue steroid during induction. Later in therapy, one may consider holding steroid until patient cardiovascular stability. Except stress doses. o Sever psychosis: Dexamethasone dose may reduce by 50% for severe psychosis. If symptoms persist, switch to prednisone. High dose methotrexate infusion guidelineHD MTX administration  Hold bactrim, NSAID, penicillins, PPI or aspirin containing medication on the day of IV MTX infusion and for at least 72 hours after start MTX infusion.  Hours -6 to 0: D5W+40-60 mEq NaHCO3/L+ 10 mEq KCL/L at 200 ml/m2/h to achieve urine pH 7-8  Hours 0 to 4: Methotrexate 8 g/m2 (Max: 20 grams) in 500 ml/m2 D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h IV over 4 hours. All doses should be round up to the next highest full gram value.Lymphoma: High dose methotrexate infusion guideline 120

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็  Hours 4 to 54: Post-hydration with D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h.  Hour 24: Begin leucovorin 15 mg/m2 PO/IV Q 6 hours. Beginning at T=24h (from the beginning of MTX infusion) and continue until serum MTX is < 0.1 uM or until delayed excretion criteria is reached.Laboratory monitoring  MTX level and serum Cr should be obtained at T= 24 H, 48H, 72H then Q 24H if delayed excreationMTX toxicity- recommendation for management For elevated MTX level or delayed excretion monitor serum creatinine q 12-24 hours and MTX level q 24 hours. Doses of leucovorin > 25 mg PO should be given IV due to saturation of absorption. Leucovorin contain calcium and should not be given at the rate faster than 160 mg per minute. During MTX administration maintain urine pH 7-8 at all times. Mucositis grading systemSeverity Stomatitis Gastritis ColitisGrade I Painless ulcers, erythema - - or mild soreness in the absence of lesionGrade II Painful erythema, edema Requiring medical management Abdominal pain with mucus and/or or ulcers but can eat or or non-surgical treatment blood in stool swallowGrade III Painful erythema, edema Bleeding without perforation, Abdominal pain, fever, change in or ulcers requiring IV uncontrolled by outpatient bowel habits with ileus or peritoneal hydration medical management, requiring signs and radiographic or biopsy hospitalization or surgery documentationGrade IV Severe ulceration or Perforation or bleeding requiring Perforation or requiring surgery or requires parenteral or emergency surgery toxic megacolon enteral nutrition support or prophylactic intubationLymphoma: High dose methotrexate infusion guideline 121

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Leucovorin rescue guidelineExcretion 24 H MTX level 48 H MTX level 72 H MTX level Leucovorin rescue/ToxicityExpected =< 10 uM < 1 uM < 0.1 uM Maintain hydration at 125 ml/m2/hexcretion 15 mg/m2 q 6 H PO/IV until MTX levelGrade I 11-49 uM 1-4.9 uM 0.1-0.49 uM < 0.1 uMMild-Delayed and/or and/or Maintain hydration at 125 ml/m2/hexcretion 25-50% increase 25-50% increase 0.5-4.9 uM 15 mg/m2 q 6 H PO/IV until MTX level Cr Cr and/or < 0.1 uMGrade I and/or and/or 25-50% increase Recheck MTX level/Cr q 24 H;Mild toxicity Grade I-II Grade I-II Cr discontinue leucovorin when MTX level stomatitis stomatitis and/or < 0.1 uMGrade II 11-49 uM 1-4.9 uM Grade I-II Increase hydration to 200 ml/m2/hModerate toxicity and/or and/or stomatitis 15 mg/m2 q 6 H PO/IV until MTX level 50-100% increase 50-100% increase 0.5-4.9 uM < 0.1 uMGrade III Cr Cr and/or Recheck MTX level/ Cr q 24 H;Severe Toxicity and/or and/or 50-100% increase discontinue leucovorin when MTX level On previous or On previous or Cr < 0.1 uM or normalized Cr or resolvedGrade IV current course of current course of and/or mucositisLife threatening HD MTX: Grade HD MTX: Grade On previous or Increase hydration to 200 ml/m2/h III-IV stomatitis, III-IV stomatitis, current course of 15 mg/m2 q 3 H IV until MTX level myelosupression myelosupression HD MTX: Grade < 0.1 uM 50-499 uM 5-99 uM III-IV stomatitis, Recheck MTX level/ Cr q 24 H; and/or and/or myelosupression discontinue leucovorin when MTX level >100% increase >100% increase 5-49 uM < 0.1 uM or normalized Cr or resolved Cr Cr and/or mucositis >100% increase >= 500 uM >= 100 uM Cr Increase hydration to 200 ml/m2/h 150 mg/m2 q 3 H IV until MTX level >= 50 uM < 0.1 uM Recheck MTX level/ Cr q 24 H; discontinue leucovorin when MTX level < 0.1 uM or normalized Cr or resolved mucositis Nephrology consultation Increase hydration to 200 ml/m2/h 1,500 mg/m2 q 3 H IV until MTX level < 0.1 uM Recheck MTX level/ Cr q 24 H; discontinue leucovorin when MTX level < 0.1 uM Nephrology consultationLymphoma: High dose methotrexate infusion guideline 122

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Supportive care guideline  Venous access o Placement of central venous access device is strongly recommended but not required.  Prophylactic antibiotics o All patient should receive prophylaxis for PCP  First line: Bactrim 5 mg/kg/day PO divided BID (Max: 320 mg TMP/day) given 3 consecutive days per week  Second line: Dapsone 1 mg/kg/day po daily (Max: 100 mg/day)  Splenectomy or splenic irradiation o All patients undergoing splenectomy or splenic irradiation should be immunized with polyvalent pneumococcal, HIB and meningococcal (unless received previously). Irradiated spleen left in situ may not be fully functional. For patients who are to have splenectomy, give vaccines prior to splenectomy. Ten to fourteen days prior to laparotomy is optimal. Penicillin prophylaxis also recommended for splenectomized patients.  HSV prophylaxis o Herpes prophylaxis (such as acyclovir 10 mg/kg BID day 5-15) should be administered for those with past history of herpestic stomatitis. Patient with mucositis on therapy should have viral culture performed and treatment started (acyclovir 750 mg/m2/day IV) if herpes is documented.  General guidelines o The uses of antiemetic and/or analgesics are allowable and encouraged as appropriate during therapy. Additional corticosteroid should be avoided as an antiemetic or pre- medication.Lymphoma: High dose methotrexate infusion guideline 123

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็ก Off therapy follow up guidelineMonths PE Lab CXR CT/PET ECHO/EKG Pul Fx Sex/Bone Renal T4/TSH Breast 0 XX X X X X XX X 3 XX X X 6 XX X X 9 XX X X 12 X X XX XX X 15 X X X 18 X X X X X X XX X 21 X X 24 X X X X XX X 30 X 36 X X X X XX X 42 X X 48 X X XX X 54 X X XX 60 X X XX 72 X XX 84 X XX 96 X XX108 X120 X  PE: physical exam to include BP, growth, Tanner staging (for all patient > 10 y/o) and closely examirradiated areas for sign of skin and secondary cancer.  Lab: CBC and ESR every visit. ALT/AST, BUN, Cr, Bilirubin and ferritin at 12 months post chemo, thenannually for 5 years.  CXR: chest x-ray  CT/PET: off therapy CT or PET scan should be limited to the original site of disease involvement forStage I and II, CT neck/chest/abdomen/pelvis should be done for Stage III and IV.  ECHO/EKG: LV function evaluation by ECHO or MUGA with EKG.  Sex/Bone: Begin sex hormone monitoring once patient is greater than 12 y/o including LH, FSH,Estradiol/Testosterone. Bone density should be done at the end of therapy then 5 and 10 years off  therapy.  Renal: for patient who received cisplatin or abdominopelvic radiation only. Checks UA, BUN, Cr ifabnormal obtain Cr clearance.  T4/TSH: serum T4 and TSH level at 0 and 6 months off therapy, then yearly for patient receivingmantel or cervical XRT.  Breast: begin semiannual breast exam at puberty and instruct in monthly self-exam.Lymphoma: Off therapy follow up guideline 124

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301]Protocol name: Thai-POG HOD 1301 Reference: COG AHOD 0431 Total Pages: 6Protocol for: Low Risk Hodgkin DiseasePatient eligibility: Low Risk Hodgkin’s Disease: o Stage I-A Hodgkin Lymphoma with no bulk disease. o Stage II-A Hodgkin Lymphoma with no bulk disease.Patient’s name HN BW Age SexHospital I II III IV kg Ht cm BSA m2Disease Status: Treatment schema:Stage: (circle one)Extranodal involvement: (circle one) Yes No LR-Induction-ISystemic symptoms: (circle one) A B drugs) LR-Induction-IIBulk disease: (circle one) Yes NoPrimary site: CT/PET/Gal RER SERPathologic subtype: LR-Consolidation-I LR-Consolidation-IPost Induction Evaluation: (circle one)CR PR SD PD CT/PET/Gal CT/PET/GalPost Induction risk group: RER SER IFRTPost Consolidation Evaluation: (circle one) CR CT/PET/GalCR PR SD PD CR PR, SDIFRT: (circle one) Yes NoIf yes, Total dose End of therapy Disease reassessmentPost IFRT evaluation : (circle one) PD patients will go to salvage protocol at any point of RxCR PR SD PDEnd of therapy date:* Please see definition on next pageLymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 125

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex kg Ht cm BSAHospital HN BW m2 Date Start:___________Phase I: LR-INDUCTION-I (3 weeks)Week 1 2 34Day 1 2 3 4 5 6 7 8 9 10 15 22 Date due Date givenMedication: DOX _______ mg IV D D Start BLEO _______/______ mg IV B B* Induction-II on day 22 VCR _______ mg IV V V or when ETOP _______ mg IV E E E blood countInvestigation: parametersCBC/diff + + + are met.ESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB + ++ECHO or MUGA and EKG +PFT + Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1 10 Units/m2/dose* 8*Vincristine (VCR) IV push over 1 minute 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 1, 2, 3 125 mg/m2/doseNoteCR = complete remission, PR= partial remission, SD = stable disease, PD = progressive diseaseRER = Rapid Early Response, SER = Slow Early ResponseABVE = Doxorubicin + Bleomycin + Vincristine + EtoposideABVE-PC = Doxorubicin + Bleomycin + Vincristine + Etoposide – Prednisolone + CyclophosphamideMIED = High dose methotrexate + Etoposide + Ifosphamide + dexamethasoneIFRT = Involved field irradiation therapyGal: Gallium scanCT is a standard for re-evaluation imaging, PET and Gal are optional for re-evaluation imagingLymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 126

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age Sex kg Ht cm BSAHospital HN BW m2 Date Start:___________Phase II: LR-INDUCTION-II (3 weeks)Start Induction-II on Day 22 of Induction-I and ANC ≥ 750/ul and PLT ≥ 75,000/ul whichever occurs later.Week 1 2 3 4 10 15 21 22Day 1 2 3 4 5 6 7 8 9 + Start Next Date due + course + Consolidation-I Date given on day 22 or when bloodMedication: count parameters are DOX _______ mg IV D D met.BLEO _______/______ mg IV B B* VCR _______ mg IV V V ETOP _______ mg IV E EInvestigation:CBC/diff + +ESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB + +CT C/A/P or PET CT Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1Vincristine (VCR) IV push over 1 minute 10 Units/m2/dose* 8* 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Note CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Induction-IIPost Induction treatment assignment: Treatment response Post induction risk group Post Induction regimen RER□ Complete Response SER □ Consolidation-I and II□ Partial response or Stable disease □ Consolidation-I and II then IFRT□ Progressive disease Progression □ Salvage protocolLymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 127

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex kg Ht cm BSAHospital HN BW m2 Date Start:___________Phase III: LR- CONSOLIDATION -I (3 weeks)Start Consolidation-I on Day 22 of Induction-II and ANC ≥ 750/ul and PLT ≥ 75,000/ul whichever occurslater.Week 1 2 34Day 1 2 3 4 5 6 7 8 9 10 15 22 Date due Date given D D StartMedication: B E V B* Consolidation- DOX _______ mg IV E II on day 22 or V when blood BLEO _______/______ mg IV + + count VCR _______ mg IV + ETOP _______ mg IV + parameters areInvestigation: + + met.CBC/diffESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB ++Echo or MUGA and EKGPFT Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1 10 Units/m2/dose* 8*Vincristine (VCR) IV push over 1 minute 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 128

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex kg Ht cm BSAHospital HN BW m2 Date Start:___________Phase IV: LR- CONSOLIDATION -II (3 weeks)Start Consolidation-II on Day 22 of Consolidation-I and ANC ≥ 750/µl and PLT ≥ 75,000/µl whicheveroccurs later.Week 1 2 3 4 10 15 21 22Day 1 2 3 4 5 6 7 8 9 + Proceed to Date due + next phase of + therapy (IFRT Date given or End ofMedication: therapy) according to DOX _______ mg IV D D End of InductionBLEO _______/______ mg IV B B* disease status VCR _______ mg IV V V ETOP _______ mg IV E E EInvestigation:CBC/diff + +ESR, E’Lyte, BUN, Cr, AST, ALT, + +TB,DBCT C/A/P or PET CT Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1Vincristine (VCR) IV push over 1 minute 10 Units/m2/dose* 8* 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Note CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Induction-IIPost Induction treatment assignment: End of Induction disease Post Consolidation management End of Consolidation treatment Status response RER □ End of therapy evaluation SER □ IFRT Complete response SER □ IFRT Any □ Salvage protocol Partial response, Stable disease ProgressionLymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 129

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name Age Sex cm BSAHospital HN BW kg Ht m2 )Phase V: INVOLVED FIELD RADIATION THERAPY (IFRT): For SER patient only Date Start:____Radiation field :(Total radiation dose :( )Number of fractions :( )Date start :( )Last day of radiation :( )CT date :( )Note  IFRT should be done within 6 weeks after start consolidation-II with ANC > 1,000/µl and Platelets > 100,000/ µl  CT chest abdomen and pelvis should be done 6-8 weeks after complete radiationPost IFRT treatment assignment: Post IFRTmanagement Post radiation treatment response Complete response □ End of therapy evaluation Partial response, Stable disease □ Disease reassessment: repeat biopsy or PET scan to Progression evaluate residual disease □ Salvage protocolLymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 130

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302]Protocol name: Thai-POG HOD 1302Reference: COG AHOD0831, St. Jude’s MIEDProtocol for: Intermediate Risk/High Risk Hodgkin Disease Total Pages: 8Patient eligibility: Intermediate Risk Hodgkin Disease:  High Risk Hodgkin Disease:o Stage I-E, I-B and I-A Hodgkin Lymphoma o Stage III-B Hodgkin Lymphoma. with bulk disease. o Stage IV-B Hodgkin Lymphoma.o Stage II-E-, II-B and II-A Hodgkin Lymphoma with bulk disease.o Stage III-A Hodgkin Lymphoma.o Stage IV-A Hodgkin Lymphoma.Patient’s name Age SexHospital HN BW kg Ht BSADisease Status: Treatment schema:Stage: (circle one) I II III IV HR-Induction-I drugs)Extranodal involvement: (circle one) Yes No HR-Induction-IISystemic symptoms: (circle one) A BBulk disease: (circle one) Yes No CT/PET/GalBMA and Biopsy (only >= II-B):Site involvement: Risk group: RER SERPathologic subtype: CR PR SD PDDisease stage: HR-Consolidation-I HR-Intensification-IPost Induction Evaluation: HR-Consolidation-II HR-Intensification-II Post induction risk group: RER SER CT/PET/Gal CT/PET/GalPost Intensification Evaluation: ***SER only CR CR, PR, SDCR PR SD PDPost Consolidation Evaluation: HR-Consolidation-ICR PR SD PD HR-Consolidation-IIIFRT Date: Total dose CT/PET/GalPost IFRT evaluation: (circle one)CR PR SD PD CR, PR, SD IFRTEnd of therapy date: CR, PR, SD IFRT CT/PET/Gal* Please see definition on the next page CT/PET/Gal CR PR, SD Disease reassessment End of therapy PD patients will go to salvage protocol at any point of RxLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 131

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age Sex kg Ht cm BSAHospital HN BW m2 Date Start:___________Phase I: HR-INDUCTION-I (3 weeks)Week 1 23 4Day 1 2 3 4 5 6 7 8 9 10 15 22 Date due Start Induction- Date given II on day 22 or whenMedication: blood DOX _______ mg IV D D count parametersBLEO _______/______ mg IV B B* are met. VCR _______ mg IV V V ETOP _______ mg IV E E E PRED _____ mg PO BID CPM _______ mg IV C C G-CSF _______ mcg SQ/IV G GInvestigation: + ++ + ++CBC/diff +ESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +ECHO or MUGA and EKGPFT Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1 10 Units/m2/dose* 8*Vincristine (VCR) IV push over 1 minute 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Prednisone (PRED) PO 1-7Cyclophosphamide (CPM) IV over 30-60 minutes 20 mg/m2/dose BID 1, 2 600 mg/m2/doseG-CSF SubQ or IV 5 mcg/kg/dose Daily begin on day 4 Hold on day 8Note Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul post nadir. Do not give on day 8.Note  CR = complete remission, PR= partial remission, SD = stable disease, PD = progressive disease  RER = Rapid Early Response, SER = Slow Early Response  ABVE = Doxorubicin + Bleomycin + Vincristine + Etoposide  ABVE-PC = Doxorubicin + Bleomycin + Vincristine + Etoposide – Prednisolone + Cyclophosphamide  MIED = High dose methotrexate + Etoposide + Ifosphamide + dexamethasone  IFRT = Involved field irradiation therapy  Gal: Gallium scan  CT is a standard for re-evaluation imaging, PET and Gal are optional for re-evaluation imagingLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 132

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name HN BW Age SexHospital kg Ht cm BSA m2Phase II: HR-INDUCTION-II (3 weeks) Date Start:___________Last day of G-CSF:Start Induction-II on Day 22 of Induction-I and ANC ≥ 750/ul (at least 2 days after stop G-CSF) and PLT ≥75,000/ul whichever occurs later.Week 1 23 4Day 1 2 3 4 5 6 7 8 9 10 15 21 22 Date due Start Next course Date given (Intensification-Medication: I or DOX _______ mg IV D D Consolidation-I) on day 22 orBLEO _______/______ mg IV B B* when blood count VCR _______ mg IV V V parameters are ETOP _______ mg IV E E met. PRED _____ mg PO BID (+) CPM _______ mg IV C C G GG-CSF _______ mcg SQ/IVInvestigation: + ++ + ++CBC/diffESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +CT C/A/P or PET CTBM aspiration and biopsy Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) 5 Units/m2/dose IV over 10 minutes 10 Units/m2/dose* 1 1.4 mg/m2/dose 8*Vincristine (VCR) IV push over 1 minute 125 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 20 mg/m2/dose BID 1, 2, 3Prednisone (PRED) PO 600 mg/m2/dose 1-7Cyclophosphamide (CPM) IV over 30-60 minutes 1, 2G-CSF SubQ or IV 5 mcg/kg/dose Daily begin on day 4 Hold on day 8Note Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul post nadir. Do not give on day 8. CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Induction-II BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement at diagnosisPost Induction treatment assignment: Treatment response Disease Status Post Induction regimen□ Complete Response RER □ Consolidation-I and II□ Partial response or Stable SER □ Intensification-I and II then Consolidation-I and IIdisease□ Progressive disease Progression □ Salvage protocolLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 133

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name HN Age SexHospital BW kg Ht cm BSA m2Phase V: HR-CONSOLIDATION-I (3 weeks): RER: start after Induction-II/ SER: startSatfatertrCIonntseonlisdiafitcioant-iIoonn-DIaIy 22 of Induction-II in RER or IntensificatioDn-aIItien SSEtaRrat:n_d_A_N_C__≥__75_0_/_ul (atleast 2 days after stop G-CSF) and PLT ≥ 75,000/ul whichever occurs later.Week 1 2 34Day 1 2 3 4 5 6 7 8 9 10 15 22 Date due Date givenMedication: DOX _______ mg IV D DBLEO _______/______ mg IV B B* Start VCR _______ mg IV V V Consolidation- ETOP _______ mg IV E E E II on day 22 or when blood PRED _____ mg PO BID count CPM _______ mg IV C C G parameters areG-CSF _______ mcg SQ/IV G met.Investigation: + ++ + ++CBC/diff +ESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +Echo or MUGA and EKGPFT Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) 5 Units/m2/dose IV over 10 minutes 1 10 Units/m2/dose* 8*Vincristine (VCR) IV push over 1 minute 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Prednisone (PRED) PO 20 mg/m2/dose BID 1-7Cyclophosphamide (CPM) IV over 30-60 minutes 600 mg/m2/dose 1, 2G-CSF SubQ or IV 5 mcg/kg/dose Daily begin on day 4 Hold on day 8Note Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul post nadir. Do not give on day 8.Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 134

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name HN BW Age Sex m2Hospital kg Ht cm BSAPhase VI: HR-Consolidation-II (3 weeks) Date Start: Last day of G-CSF:Start Consolidation-II on Day 22 of Consolidation-I and ANC ≥ 750/ul (at least 2 days after stop G-CSF)and PLT ≥ 75,000/ul whichever occurs later.Week 1 23 4Day 1 2 3 4 5 6 7 8 9 10 15 21 22 Date due Proceed to next phase of Date given therapyMedication: (IFRT or salvage DOX _______ mg IV D D protocol) according toBLEO ______/______ mg IV B B* End of VCR _______ mg IV V V Consolidation ETOP _______ mg IV E E E evaluationPRED _____ mg PO BID (+) CPM _______ mg IV C C G GG-CSF _______ mcg SQ/IVInvestigation: + ++ + ++CBC/diffESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +CT C/A/P or PET CTBM aspiration and biopsy Drug Route Dosage DaysDoxorubicin (DOX) IV push over 5 minutes 25 mg/m2/dose 1, 2Bleomycin (BLEO) IV over 10 minutes 5 Units/m2/dose 1Vincristine (VCR) IV push over 1 minute 10 Units/m2/dose* 8* 1.4 mg/m2/dose 1, 8Etoposide (ETOP) IV over 60-120 minutes 125 mg/m2/dose 1, 2, 3Prednisone (PRED) PO 20 mg/m2/dose BID 1-7Cyclophosphamide IV over 30-60 minutes 600 mg/m2/dose 1, 2(CPM)G-CSF SubQ or IV 5 mcg/kg/dose Daily begin on day 4 Hold on day 8Note Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul post nadir. Do not give on day 8. CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Consolidation-II BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement at diagnosisPost Induction treatment assignment: Treatment response Post Consolidation management□ Complete Response/ Partial Response/ Stable disease □IFRT□ Progressive disease □Salvage protocolLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 135

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name HN Age SexHospital BW kg Ht cm BSA m2Phase III: HR-INTENSIFICATION-I (3 weeks):Only for SER: start after Induction-II Date Start: __________SPtLaTrt≥In7te5n,0s0i0fi/cualtwiohni-cIhoenveDraoyc2c2uorsf Ilnatdeurc. tion-II and ANC ≥ 750/ul (at least 2 days after stop G-CSF) andWeek 12 34Day 1 2 3 4 5 6 7 8 9 10 15 22 Date due Start Intensification-II Date given on day 22 orMedication: when bloodHD-MTX _______ mg IV M count parameters areLCV _______ mg IV/PO LLLLLLLLLL ETOP _______ mg IV LL met. EEE IFOS _______ mg IV III MESNA _______ mg IV SSS SSS SSS DEX _______ mg IV DDD DDDG-CSF _______ mcg SQ/IV DDD GInvestigation: + ++ + ++CBC/diff +ESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +Echo or MUGA and EKGPFT Drug Route Dosage DaysHigh-dose IV drip in 4 hours 8,000 mg/m2/day Day 1Methotrexate (HD-MTX) IV/PO 15 mg/m2/dose q 6 hours Day 2, 3, 4Leucovorin (LCV) IV over 60-120 minutes 200 mg/m2/day Day 2, 3, 4Etoposide (ETOP) IV over 4 hours 2,000 mg/m2/day Day 2, 3, 4Ifosfamide (IFOS) IV 500 mg/m2/dose Day 2, 3, 4MesnaDexamethasone (DEX) IV At hour 0, 3, 6 of IFOS 40mg/m2day divided in 3 dose Day 1, 2, 3 q 8 hoursG-CSF SubQ or IV 5 mcg/kg/day Day 4 then dailyNote: Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul post nadir.Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 136