CPG มะเร็งเม็ดเลือดขาวและต่อมน้ำเหลืองในผู้ใหญ่

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<ul><li><p> ( Categories of Consensus ) </p><p>1. Acute Lymphoblastic Leukemia in Adult (ALL) 2. Multiple Myeloma (MM) 3. Non-Hodgkins Lymphoma (NHL) 4. Chronic Myeloid Leukemia (CML) 5. Acute myeloid leukemia (AML) 6. Hodgkins Disease (HD) </p></li><li><p> 2549 </p></li><li><p> 1. .. 2. .. 3. .. 4. .. 5. .. 6. .. 7. .. 8. . . 9. .. 10 .. 11 .. 12 . </p></li><li><p> ( Categories of Consensus ) </p><p> 2 (strength of evidence) (consensus) </p><p>1 2A 2B 3 </p><p> 1 : ( randomized clinical trials meta analysis) </p><p> 2A : 1 ( phase II Cohort retrospective studies ) </p><p> 2 B : 1 2 A 2 B 1 </p><p> 3 : 3 2 randomized trial 3 </p><p>: NCCN 2004 </p></li><li><p>Acute Lymphoblastic Leukemia </p></li><li><p> 2549 : </p><p>2</p><p> 3 ALL 4 </p><p> ALL 6 7 11 </p><p>1. ALL 10 2. adult ALL 16 </p><p> induction of remission 3. adult ALL post remission 19 4. CNS prophylaxis/ CNS leukemia 21 5. adult ALL remission 22 </p><p> 1. French-American-British classification of ALL15 4 </p><p>2. Immunophenotype adult ALL18-20 5 3. Adverse prognostic factors in adult ALL16 7 4. Supportive care ALL 12 5. monitoring 13 </p><p> Regimen Chemotherapy 25 30 </p></li><li><p> 2549 : </p><p>3</p><p>Acute Lymphoblastic Leukemia in Adult Acute lymphoblastic leukemia (ALL) lymphoid lymphoblast neutropenia ALL 2-10 20 ALL1 ALL ALL French-American British (FAB) classification2 immunophenotype3-6 (cytogenetics) (molecular genetics) ALL immunophenotype cytogenetics 7-10 ALL 11 12 ALL cranial neuropathies ( cranial nerve 3, 4, 6 7 )13 papilloedema T-lineage ALL </p></li><li><p> 2549 : </p><p>4</p><p>mediastinal mass superior vena cava syndrome 14 lymphoblast lymphoblast lymphoblast WHO lymphoblast 20% ALL 6 ALL ALL 1. Morphological classification </p><p> FAB classification6 3 cytochemistry 3 1 cytochemistry ALL L1 L2 immunophenotyping L3 B-lineage (B-ALL) Burkitts lymphoma WHO ANLL L3 ALL immunophenotyping </p></li><li><p> 2549 : </p><p>5</p><p> 1 French-American-British classification of ALL15 FAB L1 FAB L2 FAB L3 (Burkitt) Morphology Nuclear/Cytoplasmic ratio Nucleoli Vacuolization cytoplasm </p><p> &gt; 75% 0-1 </p><p> &gt; 25% &gt; 1 </p><p>Cytochemistry Myeloperoxidase Nonspecific esterase Periodic acid-Schiff Acid phosphatase </p><p> - + + + </p><p> - + + + </p><p> - - - - </p><p> 2. Immunophenotyping3-7 WHO classification6 ALL immunophenotype 16 immunophenotyping ALL 2 B-cell ALL T-cell ALL17 75 ALL B-cell ALL immunophenotype marker ALL ANLL TdT cell lymphoid TdT mature B-ALL B-lineage markers CD 19, CD 20, CD 22, CD 24 CD 79a T-cell ALL 25 T-lineage markers CD2, CD3, CD1a, CD4, CD5, CD7 CD 8 ALL immunophenotype 2 </p></li><li><p> 2549 : </p><p>6</p><p> 2 Immunophenotype adult ALL18-20 </p><p>Lineage TdT HLA-DR </p><p>CD34 CD19 CD22 CD79a CD10 cy cyk/ sIgH/L cyCD3 CD7 CD1a CD2 CD5 sCD3 </p><p>Precursor-B-cell ALL Pro-B ALL cALL Pre-B ALL </p><p> + + + </p><p> + + + </p><p> + - - </p><p> + + + </p><p> + + + </p><p> + - - </p><p> - + + </p><p> - - + </p><p> - - - </p><p> - - - </p><p>Transitional Precursor-B-cell ALL </p><p> + </p><p> + </p><p> - </p><p> + </p><p> + </p><p> - </p><p> - </p><p> - </p><p> - </p><p> + </p><p>Mature B cell ALL - + - + + - - - + + T-lineage ALL Pro-T ALL Pre-T ALL Cortical-T ALL Mature-T ALL </p><p> + + + + </p><p> + + - - </p><p> + + - - </p><p> + + + + </p><p> + + + + </p><p> - - + - </p><p> - + + + </p><p> - + + + </p><p> - - - + </p><p>3. Cytogenetics/Molecular genetics21 </p><p> cytogenetics ALL ALL ALL (L2) CD 10+ pre-B ALL 25-50 Philadelphia chromosome : t(9;22) ALL(L3) chromosome 8 t(8;14) 90, t(8;22) 10 ALL t(4;11) 3-4 chromosome hyperleukocytosis ALL ALL bone marrow failure (complete remission) 70-85 10-20 20-40 immunophenotype </p></li><li><p> 2549 : </p><p>7</p><p> ALL 3 3 Adverse prognostic factors in adult ALL16 Clinical characteristics 60 </p><p> 30 x 109/ Immunophenotype Pro B (B-lin, CD 10-) </p><p>early T* ( T-lin, CD1a-,sCD3-) mature T (T-lin, CD1a-,sCD3+) </p><p>Cytogenetics / molecular genetics t(9;22) / BCR-ABL or t(4;11)/ALLI-AF4 Treatment response complete response 4 </p><p> Standard risk group = no risk factor , High risk group &gt; 1 risk factor * early T = pro-T ALL or pre-T ALL </p><p> ALL ALL AML </p><p> ALL ALL 1. Complete Blood Count </p><p> acute leukemia </p></li><li><p> 2549 : </p><p>8</p><p> blast cells (aleukemic leukemia) </p><p>2. (bone marrow examination) </p><p> ALL </p><p> morphology cytochemistry ALL ANLL </p><p>lymphoblast myeloperoxidase (MPO) 3-5% MPO </p><p> immunophenotype ALL immunophenotype marker ALL ANLL terminal deoxynucleotidyl transferase (TdT) </p><p> (cytogenetic evaluation) </p><p> 3. (molecular genetics evaluation) </p><p> ALL Philadelphia chromosome positive Bcr/Abl PCR </p><p> CBC &amp; platelet count </p></li><li><p> 2549 : </p><p>9</p><p> : FPG, BUN, Cr, LFT, LDH, Ca++, PO4, electrolytes, uric acid Coagulation studies/D-dimer Chest X-rays HBs Ag, anti HCV, anti HIV, Urine, stool examination EKG Type and screening for cross-match </p><p> 45 echocardiography MUGA scan (cardiac ejection fraction ) HLA typing unit lymphocytotoxic antibody 1 </p></li><li><p> 2549 : </p><p>10</p><p> 1 ALL </p><p> . . </p><p>-CBC &amp; Blood smear ( ALL emergency conditions ) . </p><p>- CBC &amp; Blood smear morphology, differential count - Bone marrow </p><p> Wrights stain morphology Cytochemistry Cytogenetics </p><p>- flow immunophenotyping </p><p>- Molecular marker (BCR-Abl) </p><p> : FPG, BUN, Cr, LFT, LDH, </p><p>Ca++, PO4, electrolyte, uric acid Chest X-rays HBs Ag, anti HCV, anti HIV, Urine, stool examination EKG </p><p> HLA typing platelet </p><p>transfusion hematopoietic stem cell transplantation </p><p> Lymphocytotoxic (anti HLA) antibody unit </p><p> Screening for Herpes simplex , CMV Echocardiography MUGA scan for cardiac </p><p>ejection fraction anthracycline </p><p> LP papilloedema cranial nerve involvement </p><p> 2A </p></li><li><p> 2549 : </p><p>11</p><p> 1. </p><p> packed red cells hematocrit 24-25% 60 hematocrit 28-30% 100 x 109 /L hyperleukocytosis ALL hyperleukocytosis ANLL </p><p> 10x109/L 20x109/L </p><p> leukocyte poor leukocyte depleted non-hemolytic transfusion reaction , cytomegalovirus infection alloimmunization </p><p> ( &gt; 38oC ) </p><p> ( febrile neutropenia) </p><p> 100x109/L leukostasis corticosteroid </p></li><li><p> 2549 : </p><p>12</p><p>(leukocrit &gt; 10%) leukostasis leukapheresis leukapheresis 25-50% </p><p> tumor lysis syndrome tumor lysis syndrome 2-3 </p><p> allopurinol 300 mg/d </p><p> 4 5 4 Supportive care ALL </p><p> supportive care </p><p> prophylaxis antibiotics antifungal prophylaxis G-CSF intensive high dose chemotherapy 60 febrile neutropenia ( CR G-CSF 7 ) </p><p> leukocyte-depleted products RBC Hb 8.0 g/dL platelet 10x109/L SCT screening CMV </p><p> tumor lysis syndrome hydration , urine alkalinization allopurinol high dose cytarabine HDMTX steroid eye drop 24 </p><p> High dose cytarabine o 60 renal impairment High dose cytarabine </p><p> cerebellar toxicity o cerebellar signs </p><p> o tumor lysis syndrome Cr. high dose cytarabine o high dose cytarabine </p><p>dose High dose cytarabine </p></li><li><p> 2549 : </p><p>13</p><p> 5 monitoring </p><p> 2. </p><p> CNS </p><p> Induction of remission </p><p> CBC, platelet count ( 0.5x109/L differential count leukemic cell platelet count ) Blood chemistry, electrolytes, BUN, Cr, uric acid, PO4 tumorlysis syndrome. (WBC 50 x 109/L, ) nephrotoxic agent renal impairment monitor CBC induction of remission complete remission cytopenia 14 blast cells hypoplasia 10-14 </p><p> Post remission consolidation / Intensification therapy </p><p> CBC , Platelet count Blood chemistry, electrolytes, BUN, Cr, uric acid, PO4. 2 CBC 5 </p></li><li><p> 2549 : </p><p>14</p><p> 4 Remission induction phase Consolidation / Intensification phase Maintenance phase CNS therapy </p><p> Remission induction phase </p><p> 3 vincristine, anthracycline (doxorubicin </p><p> daunorubicin), steroid (category recommendation 2A) vincristine prednisone CR 40-65 </p><p> 3-7 anthracycline daunorubicin doxorubicin CR 72-92 18 22-28 idarubicin daunorubicin doxorubicin myelotoxicity 29-31 </p><p> 4 -6 adult ALL induction of remission L-asparaginase, cyclophosphamide, etoposide, high dose cytarabine (HIDAC) high dose methotrexate (HDMTX) CR 80 CR 9,16,26,32-40 CR 90 low risk 75 intermediate risk RCT vincristine, anthracycline ,steroid + cyclophosphamide L-asparaginase </p><p>Kantarjian adult ALL Hyper-CVAD regimen HDMTX HIDAC 204 CR induction of remission 91 6 38 5 37 </p><p> GIMEMA 0288 794 38 cyclophosphamide CR vincristine, prednisone, daunorubicin, L-</p></li><li><p> 2549 : </p><p>15</p><p>asparaginase ( 83 81) cyclophosphamide 8 28 </p><p> LALA-94 922 41 idarubicin daunorubicin adult ALL induction of remission 4 (vincristine, prednisone, anthracycline, L-asparaginase) CR ( 71 72) ( 5 2) idarubicin median DFS 31.1 18.2 daunorubicin </p><p> dexamethasone prednisolone induction of remission lymphoblast 42-44 </p><p> L-asparaginase vincristine, anthracycline steroid CR adult ALL induction of remission CR 45 </p><p> RCT 3 growth factor (G-CSF) induction of remission46-49 febrile neutropenia CR 60 anthracycline 3 G-CSF 5 g/kg (category recommendation I ) </p><p> Burkitts ALL (L3 morphology, surface Ig expression, t(14;18)) 3 4 CR 44 relapse induction of remission intensive short course 6 CR 50-52 Stanford </p></li><li><p> 2549 : </p><p>16</p><p>regimen, Hyper-CVAD, CALGB 9251, CODOX-M/IVAC, BNHL-86 CR 75-92 4 50-70 (category recommendation 2A ) </p><p> adult T-cell leukemia G-CSF CR 35-36 8-13 53,54 adult T-cell leukemia zidovudine Interferon alpha 80 50 CR HTLV-I mediastinal mass mediastinum (category recommendation 2B ) protocol adult ALL induction B cell ALL Burkitts type 3 vincristine, anthracycline steroid anthracycline doxorubicin daunorubicin steroid dexamethasone prednisolone L-asparaginase cyclophosphamide Burkitts ALL T-cell ALL (intensive short course regimen) 60 HIDAC, HDMTX G-CSF 5 g/kg </p></li><li><p> 2549 : </p><p>17</p><p> 2 adult ALL induction of remission </p><p>Conventional dose chemotherapy regimen </p><p> Anthracycline1, Vincristine, Steroid2 </p><p> L-asparaginase Cyclophosphamide 4-6 </p><p>LP3 MTX, Ara-C CNS prophylaxis blast cranial radiation </p><p>CR CBC Blood chemistry LFT LP Blast cell </p><p> Hb &gt; 10 g/dL Platelet &gt; 100x109/L PMN &gt; 1.5x109/L Blast cell </p><p>cellularity &gt; 25% Blast &lt; 5% </p><p>Blast 5-25% </p><p>Blast &gt;25% </p><p>PR </p><p>Refractory </p><p>Post remission treatment5 </p><p>Induction 2 </p><p>Salvage therapy </p><p>High dose chemotherapy Regimen HDAC, HDMTX HD VP-16 </p><p>60 </p><p> KPS </p><p>Low dose chemotherapy Vincristine , steroid Best supportive care </p><p>1. Anthracycline Daunorubicin Doxorubicin Idarubicin Mithoxantrone IV push 3 (Recommended level 2A) </p><p>2. Steroid Prednisolone Dexamethasone Dexamethasone lymphoblast CSF (Recommended level 2B) 3. LP early CNS prophylaxis induction therapy blast cell (Recommended level 2B) 4. Burkitts ALL Intensive high dose chemotherapy CR post remission therapy (Recommended level 2A) 5 3 </p></li><li><p> 2549 : </p><p>18</p><p> induction of remission 2 Consolidation/Intensification phase </p><p> remission subclinical minimal residual disease post-induction consolidation-intensification multi-agent drugs consolidation/intensification post-remission therapy randomized trials consolidation CR nonrandomized historical control studies consolidation high risk CR post-remission therapy multi-agent drugs55,56 </p><p> consolidation/intensification post-remission therapy randomized trials 2 GIMEMA ALL 0288 study38 PETHEMA ALL-89 trial57 DFS late consolidation/intensification therapy </p><p> consolidation induction chemotherapy AML (7+3) LFS randomized trial intensive consolidation standard therapy CR 74 consolidation AML (cytarabine 7 daunorubicin 3 ) x 2 maintenance therapy 6-mercaptopurine methotrexate 77 maintenance therapy intensification remission58 </p><p> HIDAC intensification therapy LFS consolidation ( LFS 26-50%) poor risk 59 ECOG 2483 348660 HIDAC 3 g/m2 12 6 MACHO (cyclophosphamide, doxorubicin, vincristine, prednisone, methotrexate, L-asparaginase) x 8 maintenance therapy DFS 10 DFS 4 13% HIDAC survival maintenance therapy </p><p> high dose MTX consolidation/intensification LFS 41% (31-56%) HIDAC HDMTX LFS 32% CNS prophylaxis </p><p> randomized trial European Organization for Research and Treatment of Cancer (EORTC) CR long (3 ) short (1 ) consolidation long consolidation therapy L-10 protocol Memorial Sloan-Kettering Cancer Center (MSKCC) short consolidation L-asparaginase cyclophosphamide 5-7 CR </p></li><li><p> 2549 : </p><p>19</p><p>40%61 nonrandomized intensive multi-agent post remission therapy CALGB study 8811 197 32 remission early late intensification 8 dose-intense, multi-course treatment cranial irradiation intra-thecal methotrexate maintenance 2 CR 85% 36 26 </p><p> multicenter consolidation therapy HDMTX standard risk B-ALL , cyclophosphamide ara-C T-cell ALL , HDMTX HDAC high risk B-ALL intensive consolidation LFS high risk pro-B-ALL long term CR 40 high risk 1962 </p><p> consolidation regimen regimen GMALL 562 CR 75% LFS 35% 10 16 CALGB 8811 197 CR 85% LFS 30% 5 9 GIMEMA 0228 (2002) 778 CR 82%, LFS 34% 8 38 consolidation/intensification therapy Low risk consolidation therapy regimen high risk consolidation therapy HDAC , HDMTX HD-etoposide (category recommendation 2A ) adult ALL post remission therapy 3 </p></li><li><p> 2549 : </p><p>20</p><p> 3 adult ALL post remission Risk group1 Consolidation/intensification2 Maintenance3 </p><p> HLA match donor </p><p>Intensive chemotherapy HDAC, HDMTX high dose VP-16 </p><p>Conventional dose chemotherapy </p><p>KPS4 </p><p>KPS </p><p>Intermediate /high risk </p><p>Low risk </p><p> HLA match donor </p><p>Allogeneic SCT </p><p>6-MP oral MTX oral </p><p> Vincristine, Prednisolone MTX intra-thecal 3 CBC, LFT (keep WBC 2.5-3.0 x 109/L) 2 </p><p>CR 4 </p><p>Relapse Salvage therapy </p><p>1. Risk group 3 2. conventional dose chemotherapy GMALL 84/02 , CALGB 8811 regimen...</p></li></ul>