淋巴癌診療指引 2012 年 01 月 18 日制定 2013 年 01 月 16 日一修 2014 年 01 月 29 日二修 淋巴癌醫療團隊共同制定

Transcription

1 淋巴癌診療指引 淋巴癌醫療團隊共同制定

2 修訂原則 參與修訂科別 : 血液暨腫瘤內科 腫瘤治療科 放射診斷 科 病理科 安寧緩和團隊 診療指引需符合以下原則 : 一 依據實證醫學精神, 並於指引中註明主要參考文獻 ( 至少為 peer review article ), 若引用醫院之資料庫資料, 則需提供分析及討論紀錄 二 參酌國情並經院內共識討論, 且有相關會議紀錄佐 三 定期檢視改版 ( 至少每年一次, 且明確標示制訂或修訂日期 ) 四 團隊共識後所訂之指引, 應提送癌委會核備後公告

3 本診療原則是提供醫師及其他醫療人員診斷與治療淋巴瘤參考之用, 並不一定適用於所有淋巴瘤病人 診療方式仍應由瞭解病情之負責醫師來決定

4 Classification of Lymphoma (adopted from 2008 WHO classification) 淋巴瘤分類

5 WHO 2008 Lymphoid Neoplasm Classification Precursor Lymphoid Neoplasms Mature B-Cell Neoplasms Mature T-Cell & NK-Cell Neoplasms Hodgkin lymphoma (Hodgkin disease) Post-Transplant Lymphoproliferative Disorders (PTLD) Histiocytic and Dendritic Cell Neoplasms 淋巴瘤分類

6 Hodgkin lymphoma (Hodgkin disease) 淋巴瘤分類

7 Mature B-Cell Neoplasms Chronic lymphocytic leukemia / small lymphocytic lymphoma B-cell prolymphocytic leukemia Splenic marginal zone lymphoma Hairy cell leukemia Lymphoplasmacytic lymphoma / Waldenstrom macroglobulinemia Heavy chain disease Plasma cell myeloma Solitary plasmacytoma of bone Extraosseous plasmacytoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type Nodal marginal zone lymphoma Follicular lymphoma Primary cutaneous follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma, NOS (T-cell / histiocyte-rich type; primary CNS type ; primary leg skin type & EBV+ elderly type) Diffuse large B-cell lymphoma with chronic inflammation Lymphomatoid granulomatosis Primary mediastinal large B-cell lymphoma Intravascular large B-cell lymphoma ALK+ large B-cell lymphoma Plasmablastic lymphoma Large B-cell lymphoma associated with HHV8+ Castleman disease Primary effusion lymphoma Burkitt lymphoma B cell lymphoma, unclassifiable, Burkitt-like B cell lymphoma, unclassifiable, Hodgkin lymphomalike 淋巴瘤分類

8 Ann Arbor Staging System (adopted from NCCN guideline V ) 淋巴瘤分期

9 淋巴瘤分期

10 Ann arbor staging system 淋巴瘤分期

11 Prognostic factors & Risk factors

12 Unfavorable Risk Factors for Stage I-II Hodgkin Lymphoma 預後評估

13 Advanced Hodgkin Lymphoma International Prognostic Score (adopted from NCCN guidline V ) 預後評估

14 International Prognostic Score (IPS) 1 point per factor Albumin < 4 g/dl Hemoglobin < 10.5 g/dl Male Age 45 years Stage IV disease Leukocytosis (WBC 15000/ μl) Lymphocytopenia (lymphocyte count less than 8% of WBC, and/or lymphocyte count less than 600/μL) 預後評估

15 Diffuse Large B cell Lymphoma International Prognostic Index (IPI score) (adopted from NCCN guidline V ) 預後評估

16 International Prognostic Index Age-Adjusted International Prognostic Index 預後評估

17 Follicular lymphoma International Prognostic Index (adopted from NCCN guidline V ) 預後評估

18 FLIPI Criteria 預後評估

19 仁愛醫院何杰金氏淋巴癌治療原則 (adopted from NCCN guidline V )

20 Classical Hodgkin Lymphoma Diagnosis of Hodgkin lymphoma (Excisional biopsy; FNA alone is generally insufficient) Workup: Physical exam Performance status/b symptoms CBC, DC Biochemistry(including LDH) ESR CXR Involved area/ches/abdominal CT PET-CT scan HbsAg/anti-HBs ± anti-hbc IgG Bone marrow study Echocardogram Pulmonary function test (DLCO) Pergnancy test in women of Child-bearing age Selected cases: Neck CT, if neck RT planned HIV serum test Anti-HCV Fertility issues Classical Stage I-II Classical Stage III-IV Risk evaluation Nodular lymphocyte predominant

21 Classical Hodgkin Lymphoma Stage I-II No Risk Risk evaluation -Bulky disease:large mass (>10cm) ; size at last one third of The maximum thorax diameter -Involvement of three or more nodal areas (>3 sites) -B symptoms -ESR > 50 Any Risk

22 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Classical Hodgkin Lymphoma ABVD x 2-4 cycles + IFRT Restage after chemotherapy with PET-CT Stage IA-Stage IIA Deauville 1-3 Deauville 4 ABVD x 4 cycles Restage after with PET-CT Follow up IFRT IFRT or ABVD x 4 cycles Biospy Stage IA-IIA Deauville 1-3 Restage with PET-CT Deauville 4-5 Negative Positive Deauville 5 Biospy Deauville 1-2 ABVD x 4 cycles (total 4) Follow up Deauville 3-4 ABVD x 4 cycles (total 4) Restage with PET-CT IFRT Follow up Refractory Deauville 1-2 Follow up Biospy Deauville 3-4 Deauville 5 Biospy Follow up IFRT Negative Positive Follow up Refractory

23 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Stage III-Stage IV Classical Hodgkin Lymphoma Deauville 1-2 Stage III-IV ABVD x 2-4 cycles Restage after chemotherapy with PET-CT Deauville 3-4 ABVD x 2-4 cycles (total 6) ABVD x 2-4 cycles (total 6) Biospy Observe or RT selectively to initially bulky sites Restage with PET-CT Deauville 1-2 Negative Deauville 3-5 Positive Deauville 5 Biospy Follow up Refractory

24 Classical HD Refractory Deauville 1-3 Refractory diseaser Second-line chemotherapy ± RT Deauville 4 Deauville 5 HDT/ASCR or Observe (if HDT/ASCR contraindicated) HDT/ASCR or RT or Salvage chemotherapy ± RT or Brentuximab vedotin RT or Salvage chemotherapy ± RT or Brentuximab vedotin Deauville 1-4 HDT/ASCR or Observe (only if CR and HDT/ASCR contraindicated Deauville 5 Deauville 1-4 Deauville 5 HDT/ASCR or Observe (only if CR and HDT/ASCR contraindicated

25 PET/CT Response Criteria

26 Follow up Follow-up After Completion of Treatment up to 5 Years - Interim H&P: Every 2-4 mo for 1-2 y, then every 3-6 mo for next 3-5 y. - Laboratory studies: CBC, platelets, ESR (if elevated at time of initial diagnosis), chemistry profile every 2-4 mo for 1-2 y, then every 3-6 mo for next 3-5 y. Thyroid-stimulating hormone (TSH) at least annually if RT to neck. - Chest x-ray or CT every 6-12 mo during first 2-3 y, then chest x-ray optional. - Abdominal/pelvic CT every 6-12 mo for first 2-3 y. - Counseling: Reproduction, health habits, psychosocial, cardiovascular, breast selfexam,skin cancer risk, end-oftreatment discussion. - Surveillance PET should not be done routinely due to risk for false positives. Management decisions should not be based on PET scan alone; clinical or pathologic correlation is needed.

27 Follow up Monitoring for Late Effects After 5 Years - Interim H&P: Annually Annual blood pressure, aggressive management of cardiovascular risk factors. Pneumococcal, meningococcal, and H-flu revaccination after 5-7 y, if patient treated with splenic RT or previous splenectomy. Annual influenza vaccine. - Consider baseline stress test/echocardiogram at 10 y, especially if chest irradiation. - Consider carotid ultrasound, especially if neck irradiation. - Laboratory studies: CBC, platelets, chemistry profile annually. TSH at least annually if RT to neck. Annual lipids. - Consider chest imaging for patients at increased risk for lung cancer. - Annual breast screening: Initiate 8-10 y post-therapy, or at age 40, whichever comes first, if chest or axillary radiation. - Counseling: Reproduction, health habits, psychosocial, cardiovascular, breast selfexam,skin cancer risk. - Cardiovascular symptoms may emerge at a young age. - Treatment summary and consideration of transfer to PCP.

28 Classical HD Relapse HDT/ASCR or Observation in selected cases Negative Observation Rebiopsy Positive Restaging (same as initial work-up ± bone marrow biopsy) Initial stage IA-IIA (no prior RT with failure in initial sites) All others RT or Second-line chemotherapy ± RT Second-line chemotherapy ± RT Deauville 1-3 Deauville 4-5 Refractory

29 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Lymphocyte-predominant Hodgkin lymphoma Observe Stage IA, IIA Follow up Deauville 1-3 IFRT Restage Stage IB, IIB Observe Chemotherapy ± Rituximab ± ISRT Deauville 4-5 Observe, if asymptomatic or Second-line therapy or RTm(if no prior RT) Follow up Stage IIIA, IVA Chemotherapy ± Rituximab ± RT or Observation (category 2B) or Local RT (palliation only) Deauville 1-3 Observe Restage Stage IIIB, IVB Chemotherapy ± Rituximab ± RT Deauville 4-5 Observe, if asymptomatic or Second-line therapy or RTm(if no prior RT)

30 Lymphocyte-Predominant HD Refractory or Relapse Asymptomatic Refractory disease Asymptomatic Observe Alone or in any combination: Chemotherapy or Rituximab or RT Aggressive B-cell lymphoma Relapsed disease Biopsy negative Observe Asymptomatic Deauville 1-3 Observe Deauville 4-5 See Non-Hodgkinl lymphoma Observe or See Second-line therapy for Refractory disease (above) LPHL Symptomatic See Second-line therapy for Refractory disease (above)

31 Suggested treatment regimens Classical Hodgkin s lymphoma ABVD (Doxorubicin, Bleomycin, Vinblastine and Dacarbazine) Lymphocyte Predominant Hodgkin s lymphoma ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) ± rituximab CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) ± rituximab EPOCH (cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone) ± rituximab CVP (cyclophosphamide, vincristine, prednisone) ± rituximab Single agent rituximab

32 Classical Hodgkin s lymphoma ABVD(Ref-1) Doxorubicin (Adriamycin) 25 mg/m2 iv day1 and day15 Bleomycin 10 U/m2 iv day1 and day15 Vinblastine 6 mg/m2 iv day1 and day15 Dacarbazine (DTIC) 375 mg/m2 iv day1 and day15 (Q4W) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

33 Lymphocyte Predominant Hodgkin s lymphoma 1.ABVD ± rituximab:(ref-22,23) ± rituximab 375 mg/m2 IV 6 hour, day 1 Doxorubicin (Adriamycin) 25 mg/m2 iv day1 and day15 Bleomycin 10 U/m2 iv day1 and day15 Vinblastine 6 mg/m2 iv day1 and day15 Dacarbazine (DTIC) 375 mg/m2 iv day1 and (Q4W) 2. CHOP ± rituximab: (Ref-1,4,24) ± rituximab 375 mg/m2 IV 6 hour, day 1 Cyclophophamide 750 mg/m2 iv day 1, Doxorubicin (Adriamycin) 50 mg/m2 iv day 1, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day1-day5 (Q3W)

34 Lymphocyte Predominant Hodgkin s lymphoma 3. EPOCH ± rituximab:(ref-27,28) ± rituximab 375 mg/m2 IV 6 hour, day 1 Etoposide (VP-16) 50 mg/m2/d civi day1-4, Prednisone 60 mg/m2/d po day1-5, Vincristine 0.4 mg/m2/d civi day1-day4, Doxorubicin(Adriamycin)10mg/m2/d civi day 1-4 Cyclophosphamide 750 mg/m2 iv over 15 min d5 (Q3W) 4.Rituximab(Ref-25,26) rituximab 375 mg/m2 IV 6 hour, day 1 QW x 4 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

35 Radiation therapy40,41,42,43,44,45 IFRT Treatment type (Involved Field RT) Total dose Fraction size / # Fractions Note Hodgkin's lymphoma Combined Modality Therapy Bulky disease Hodgkin's lymphoma Combined Modality Therapy Non-bulky disease Hodgkin's lymphoma RT alone (Uncommon, except for LPHL) Conventionally Fractionated RT Conventionally Fractionated RT Conventionally Fractionated RT All stages:30-36 Gy Stage I-II: 20*-30 Gy (with ABVD) 30 Gy (with Stanford V) Stage IB-IIB: Gy Involved regions: Gy Uninvolved regions: Gy Gy/ fraction Gy/ fraction Gy/ fraction * RT 20 Gy is sufficient ESR < 50, no extralymphatic lesions, and only one or two Lymph node regions Involved. The Involved regions dose of 30 Gy is Mainly used for LPHL Non Hodgkin's lymphoma RT Conventionally Fractionated RT Intermediate / high-grade Non-Hodgkin s lymphoma (NHL) Stage I or II aggressive lymphoma: Gy Low-grade lymphoma includes Follicular lymphoma: 24-40Gy Mantle cell lymphoma: 40Gy Nasal natural killer / T-cell Lymphoma: 40-65Gy Gy/ fraction

36 Radiation therapy Note of Hodgkin's lymphoma RT Fields : When possible, the high cervical regions (all patients) and axilla (women) should be excluded from the radiation fields. Involved-field: involved lymphoid region(s) only 註 : 實際治療分次劑量 總治療次數, 應與處方劑量差異在 ±1Gy 內

37 仁愛醫院濾泡型淋巴癌治療原則 (Modified from NCCN guidline V )

38 Diagnosis of follicular lymphoma (FNA or core needle biopsy alone is not generally suitable) Workup: Physical exam Performance status B symptoms CBC, DC Biochemistry (including LDH) Involved area/chest/abdominal CT HBsAg/anti-HBs ± anti-hbc IgG Bone marrow study Pregnancy test in women of ( 女性必要 ) child-bearing age Selected cases: Anti-HCV Echocardogram PET-CT scan Beta-2 microglobulin Fertility issues Stage I,II Stage II(X) Stage III,IV

39 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Stage I,II Initial treatment IFRT Immunotherapy ± C/T ± R/T observation CR or PR Clinical follow-up Q3-6M for 5y, and then yearly Surveillance imaging Up to 2 y post completion of treatment: CT scan no more than every 6 mo >2 y: No more than annually No response Transformation to diffuse large B cell PD Clinical follow-up Q3-6M for 5y, and then yearly Surveillance imaging CT scan no more than every 6 mo >2 y: No more than annually indication of treatment Stage II(X), Stage III, IV Candidate for clinical trial Symptom (+) Threatened end-organ function Cytopenia 2nd to lymphoma Bulky disease Steady progression No indication Indicated observation PET/CT C/T + Rituximab Clinical trial Local R/T (palliation of locally symptoms) Initial response

40 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Initial Response CR or PR Consider PET/CT Rituximab maintenance up to 2 yr Clinical follow-up Q3-6M for 5y, and then yearly Surveillance imaging Up to 2 y post completion of treatment: CT scan no more than every 6 mo >2 y: No more than annually Transformation to diffuse large B cell PD No response or PD indication of treatment Candidate for clinical trial Symptom (+) Threatened end-organ function Cytopenia 2nd to lymphoma Bulky disease Steady progression Not indicated observation indicated PET/CT C/T + Rituximab Clinical trial Local R/T (palliation of symptoms)

41 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Multiple prior therapy Clinical Trial Chemotherapy ± Rituximab IFRT Best supportive care Transformation to diffuse large B cell Responsive CR High dose C/T + ASCRT AlloSCT Clinical trial Observation High dose C/T + ASCRT AlloSCT Clinical trial C/T Minimal or no prior chemotherapy (anthracycline-based) + Rituximab PET/CT PR ± R/T High dose C/T + ASCRT AlloSCT Clinical trial No response PD Clinical trial Palliative treatment Best supportive care

42 Suggested treatment regimens First-line -Bendamustine + Rituximab -R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone, Rituximab) -R-CVP (cyclophosphamide, vincristine, prednisolone, Rituximab) -Rituximab First-line for elderly or infirm -Rituximab (preferred) -Single agent alkylator (chlorambucil or cyclophosphamide) ± Rituximab First-line extended dosing -Rituximab maintenance Q12W for 8 doses by NHI Second-line -FCMR (fludarabine, cyclophosphamide, mitoxantrone, Rituximab) -Rituximab + Fludarabine Second-line extended dosing -Rituximab maintenance -High-dose therapy with autologous stem cell rescue -Allogeneic stem cell transplant only for highly selected patients 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

43 Follicular lymphoma First-line(Ref-2) 1. Bendamustine + Rituximab: ± rituximab 375 mg/m2 IV 6 hour, day 1 QW x 4 weeks Bendamustine 120 mg/m2 iv over 1hr d1 and 2 Q3w x 12 cycles 2.R-CHOP:(Ref-1,4,24) Rituximab 375 mg/m2 iv day1, Cyclophophamide 750 mg/m2 iv day1, Doxorubicin (Adriamycin) 50 mg/m2 iv day1, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day1-5 Q3W

44 Follicular lymphoma First-line for elderly or infirm 1. Rituximab, perferred: (Ref-16,18) 375 mg/m2 iv qw x 4 followed by q2m x 4 2. Single agent alkylator (chlorambucil or cyclophosphamide) ± Rituximab 375 mg/m2 iv q3-4weekly Chlorambucil (Leukeran) 10 mg po qd keep(ref-20) Cyclophosphamide (Cytoxan) 100 mg/m2 po qd(ref-21) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

45 Follicular lymphoma First-line extended dosing (Maintenance) 1. Rituximab, perferred: (17,18) Rituximab (375 mg/m2) once every 3 months for 2 years 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

46 Follicular lymphoma Second-line 1.FCM-R(Ref-10) Rituximab 375 mg/m2 iv day 0, Fludarabine 25 mg/m2/day iv over 30 min day1-3, Cyclophosphamide (Cytoxan) 200 mg/m2 iv over 9 hrs day1-3, Mitoxantrone 8 mg/m2 iv over 30 min d1 ( 每四週一次, 共 4 個療程 ) 2. FR(Rituximab/ Fludarabine)(Ref-11) Epirubicin 50mg/m2, iv over 10 min,day 1 Cisplatin 60mg/m2, iv over 6 hour, day 1 Fluorouracil 1200mg/m2, iv CI over 48 hour, day 1 ( 每三週一次 ) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

47 仁愛醫院瀰漫性大型 B 細胞淋巴癌治療原則 (modified from NCCN guideline V )

48 Diagnosis of diffuse large B cell lymphoma (FNA or core needle biopsy alone is not generally suitable) Workup: Physical exam Performance status B symptoms CBC, DC Biochemistry (include LDH, Uric acid) Involved area/chest/abdominal CT PET-CT scan HBsAg/anti-HBs ± anti-hbc IgG Bone marrow study Echocardogram Pregnancy test in women of child-bearing age Selected cases: Beta-2 microglobulin (option) Fertility issues HIV Anti-HCV Lumbar puncture, if paranasal sinus, testicular, epidural, bone marrow with large cell lymphoma, HIV lymphoma, 2 extranodal sites and elevated LDH Induction chemotherapy

49 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Induction therapy Non-bulky < 10cm RCHOP 3 cycles + locoregional R/T RCHOP 6 cycles ± locoregional R/T Stage I, II Pre-RT evaluation Bulky >10cm Stage III, IV RCHOP Clinical trial RCHOP 6 cycles ± locoregional R/T After 2-4 cycles Interim restaging In testicular lymphoma, after completion of C/T, R/T should be given to contralateral testis. In selected settings (paranasal sinus, testicular, epidural, bone marrow with large cell lymphoma, HIV lymphoma,or 2 extranodal sites and elevated LDH), intrathecal C/T may be given for CNS prophylaxis.

50 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Pre-RT evaluation Follow-up therapy CR PET-Negative Stage I, II: Pre RT evaluation, repeat all positive studies. If PET-CT scan positive, rebiopsy before changing course of treatment. End of treatment restaging Clinical follow-up Q3-6M for 5y, and then yearly Complete planned course CR PR PET-positive PD Complete course with higher dose R/T high dose C/T + ASCR± R/T Clinical trial Repeat all positive studies PR PD Relapse or refractory disease R/T in selected patient who are not candidates for C/T

51 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Interim restaging Follow-up therapy End of treatment restaging Observation Consider R/T for initial bulky disease High dose therapy with ASCR Clinical follow-up Q3-6M for 5y, and then yearly Image Study CT scan no more often than every 6 mo for 2 y after completion of treatment, then only as clinically indicated Respending cases Stage III, IV After 2-4 cycles, Repeat all positive studies CR Complete RCHOP 6 cycles Clinical trial Repeat all positive studies PR PD PD Relapse or refractory disease R/T in selected patient who are not candidates for C/T

52 仁愛財團法人 大里仁愛醫院 淋巴癌治療指引 Relapse or refractory disease High dose C/T + ASCR± IFRT Clinical trial AlloHSCT in selected cases CR Candidate for High dose therapy PR Second-line therapy Relapse or refractory disease No response Not candidate for High dose therapy Second-lineTherapy Clinical trial Palliative R/T Clinical trial Palliative treatment Best supportive care

53 Suggested treatment regimens First-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone, Rituximab) Dose dense R-CHOP14 Dose adjusted R-EPOCH (Rituximab, etoposide, prednisolone, vincrstine, cyclophosphamide, doxorubicin) First-line Therapy for patients with poor left ventricular function - RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, prednisone) - RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone) Concurrent presentation with CNS disease - Parenchymal: 3 g/m 2 or more of systemic methotrexate at count recovery as an alternating regimen - Leptomeningeal: IT methotrexate/cytarabine, consider Ommaya resevoir placement and/or systemic methotrexate (3-3.5 g/m 2 ) Second-line (candidate for ASCR) DHAP (dexmethasone, cisplatin, cytarabine) ± R ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) ± R GDP (gemcitabine, dexamethasone, cisplatin) ±R GemOx (gemcitabine, oxaliplatin) ± R ICE (ifosfamide, carboplatin,etoposide) ± R MINE (mesna, ifosfamide, mitoxantrone, etoposide) ± R Second-line (not candidate for ASCT) Clinical trial DA-EPOCH ± R CEOP (cyclophosphamide, etoposide, vincristine, prednisolone) ± R GDP ± R GemOx ± R Lenalidomide ± R Rituximab

54 Diffuse large B cell lymphoma First-line 1. R-CHOP:(Ref-1,4,24) Rituximab 375 mg/m2 iv day1, Cyclophophamide 750 mg/m2 iv day1, Doxorubicin (Adriamycin) 50 mg/m2 iv day1, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day 1-5; ( 每 3 週一次, 共 6 個療程 ) 2.Dose dense R-CHOP14:(Ref-6) Rituximab 375 mg/m2 iv day1, Cyclophophamide 750 mg/m2 iv day1, Doxorubicin (Adriamycin) 50 mg/m2 iv day1, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day1-5 ( 每 2 週一次, 共 6 個療程 )

55 Diffuse large B cell lymphoma First-line 3.Dose adjusted R-EPOCH(11) ± rituximab 375 mg/m2 IV 6 hour, day 1 Etoposide (VP-16) 50 mg/m2/d civi day1-4, Prednisone 60 mg/m2/d po day1-5, Vincristine 0.4 mg/m2/d civi day1-4, Doxorubicin(Adriamycin)10 mg/m2/d civi day1-4, Cyclophosphamide 750 mg/m2 iv over 15 min day5 ( 每 3 週一次 ) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

56 Diffuse large B cell lymphoma First-line for elderly or infirm 1. CDOP ± R(Ref-6) Rituximab 375 mg/m2 IV day1, Cyclophophamide 750 mg/m2 IV day1, PL-doxorubicin 30mg/m2, IV day 1 Vincristine 1.4 mg/m2 ( max 2 mg ) IV day1, Prednisone 40 mg/m2 po qd day 1-5; ( 每 3 週一次, 共 6 個療程 ) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

57 Diffuse large B cell lymphoma First-line Therapy for patients with poor left ventricular function 1. RCNOP (rituximab, cyclophosphamide, mitoxantrone, vincristine, prednisone)(ref-8) Rituximab 375 mg/m2 iv day1, Cyclophophamide 750 mg/m2 iv day1, Mitoxantrone 10mg/m2 iv day1, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day 1-5; ( 每 3 週一次, 共 6 個療程 ) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

58 Diffuse large B cell lymphoma First-line Therapy for patients with poor left ventricular function 2. RCEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone)(ref-7) Rituximab 375 mg/m2 iv day1, Cyclophophamide 750 mg/m2 iv day1, Etoposide 100mg/m2 iv day1-day3, Vincristine 1.4 mg/m2 ( max 2 mg ) iv day1, Prednisone 40 mg/m2 po qd day 1-5; ( 每 3 週一次, 共 6 個療程 ) 以上藥物配合淋巴癌團隊討論後制定為本院治療指引, 或有健保未給付藥物

59 Diffuse large B cell lymphoma Second-line (not candidate & candidate for ASCT) 1.ESHAP ± R(Ref-9) Etoposide(VP-16) 40mg/m2/day iv over 1hr day1-4 Methylprednisolone 500 mg/d iv over 60 min day1-5, Cisplatin (CDDP) 25 mg/m2/day ci vi day1-4, Cytarabine (Ara-C) 2000 mg/m2 iv over 2 hr day5; ( 每 3~4 週一次, 共 6~8 個療程 ) 2.Rituximab(Ref-19) Rituximab 375mg/m2, iv over 6 hour day 1

60 Diffuse large B cell lymphoma Second-line (not candidate & candidate for ASCT) 3. GDP ±R:(Ref-12) ±Rituximab 375 mg/m2 iv day1 Gemcitabine 1000 mg/m2 i.v. on days 1 and 8, Dexamethasone 40 mg orally on days 1-4, Cisplatin 75 mg/m2 i.v. on Day 1; ( 每 3 週一次 ) 4. GemOx ± R(Ref-13) ±Rituximab 375 mg/m2 iv day1, Gemcitabine 1000 mg/m2 iv day1, Oxaliplatin (Eloxatin) 100 mg/m2 iv over 2 hrs day1 ( 每 2~3 週一次, 共 8 個療程 )

61 Diffuse large B cell lymphoma Second-line (not candidate& candidate for ASCT) 5.ICE ± R(Ref-14) ±Rituximab 375 mg/m2 iv day1 Ifosfamide 5000 mg/m2 mixed with Mesna 5000 mg/m2 iv over 24 hrs day2, Carboplatin (Paraplatin) AUC 5 (max 800mg) iv d2, Etoposide (VP-16) 100 mg/m2/d iv d1-3 ( 每 2 週一次, 共 3 個療程 ) 6.MINE ± R(Ref-15) ±Rituximab 375 mg/m2 iv day1 Mesna 1330 mg/m2/d day1-3, Ifosfamide 1330 mg/m2/d iv over 1 hr day1-3, Mitoxantrone 8 mg/m2 iv day1, Etoposide (VP-16) 65 mg/m2/d iv over 1 hr day1-3 ( 每 3 週一次 )

62 Response evaluation (adopted from NCCN guideline V )

63 RESPONSE CRITERIA FOR NON-HODGKIN S LYMPHOMA (not including PET) 治療反應評估

64 REVISED RESPONSE CRITERIA FOR NON-HODGKIN S LYMPHOMA (including PET) 治療反應評估

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72 References 41.NCCN guideline Hodgkin lymphoma version NCCN guideline Non- Hodgkin lymphoma version NCCN guidline Large B cell Lymphoma version NCCN guidline Follicularl Lymphoma version