2章 急性骨髄性白血病 AML

1 2 . AML.. CQ 1 AML . CQ 2 AML . CQ 3 AML . CQ 4 AML . CQ 5 AML . CQ 6 APL . CQ 7 Down AML . 38 AML.. AML . AML. CQ1. Down AML. APL. AML Down APL . CQ7 CQ6.. t 8;21 . inv 16 .. CQ2, 3 CQ2, 3 CQ2 4. ATRA SCT.. CQ . 39.. acute myeloid leukemia AML 180. 2.. 10 . acute promyelocytic leukemia APL 25 Down AML. myeloid leukemia associated with Down syndrome ML-DS de novo AML 3 . FAB . WHO de novo AML . 70 . SCT AML . SCT APL ATRA . 90 ATO . ML-DS Down . de novo AML . APL . 40 AML.. CQ1. AML .. AML heterogeneous AML . FAB .. WHO .. 1. FAB . WHO . 1A.. May-Giemsa Wright-Giemsa . FAB .. AML . acute lymphoblastic leukemia ALL .. acute promyelocytic leukemia APL AML .. HLA-DR . CD34 CD15 AML . PML-RARA .. WHO . t 8;21 . q22;q22 /RUNX1-RUNX1T1, inv 16 . or 16;16 . t ;. q22 . /CEFB-MYH11 Monosomy 7, 5q-, 16;21 . t p11;q22 /FUS- ERG, 9;22 . t q34; /BCR-ABL, FLT3-ITD AML.

2 CQ1 41. FISH fluorescence in situ hybridization .. 2.. MLL MLL FISH .. 2.. myelodysplastic syndromes MDS .. 2B.. acute megakaryoblastic leukemia AMKL .. AML MDS 20 . 13 . Down AML myeloid leukemia associated with Down syn- drome ML-DS . t 8;21 . q22;q22 . inv 16 . or 16;16 . t ;q22 . 15;17 . q22:q12 AML 20 AML. 14 .. 2011 5 PubMed 2014 12 31 . 8 9 .. 1 acute myeloid leukemia OR acute myelogenous leukemia OR acute myeloblastic leukemia 12,248 . 2 1. cytogenetics OR gene 4,553 . 3 children OR childhood OR pediatric 806 .. 1 Grimwade D, Walker H, Oliver F, et al. The importance of diagnostic cytogenetics on outcome in AML : analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998 ; 92 : 2322-33. 2 Wheatley K, Bunnett AK, Goldstone AH, et al. A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial.

3 United Kingdom Medical Research Council's Adult and Childhood Leu- kaemia Working Parties. Br J Haematol 1999 ; 107 : 69-79. 3 Creutzig U, Zimmermann M, Ritter J, et al. Definition of a standard-risk group in children with AML. Br J Haematol 1999 ; 104 : 630-9. 42 AML. 4 Harrison CJ, Hills RK, Moorman AV, et al. Cytogenetics of childhood acute myeloid leukemia : United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 2010 ;. 28 : 2674-81. 5 Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia : the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol 2009 ; 27 : 4007-13. 6 Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/. MLL-rearranged acute myeloid leukemia : results of an international retrospective study.

4 Blood 2009 ; 114 : 2489-96. 7 Staffas A, Kanduri M, Hovland R, et al. Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia . Blood 2011 ; 118 : 5905-13. 8 Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents : recommendations from an international expert panel. Blood 2012 ; 120 : 3187-205. 9 Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Fourth Edition, World Health Organization, 2008. CQ2 43. CQ2. AML 2.. AML 1970 AML 3 7 . 3 45 mg/m2 7 100 200 mg/m2. 2 AML .. AML . AML . 90 mg/m2 3 45 mg/m2 3 .. 3 7 CD33 .. de novo AML .. 1A.. AML 3 . 45 60 mg/m2 10 12 mg/m2 . 7 10 100 200 mg/m2 2 . 2 . 80 90 1-4 AML. 5, 6 AML .. 1, 7 ANLL91 AML99 AML-05.

5 150 mg/m2 5 200 mg/m2 12 7. 5 mg/m2 5 . 8 AML . 1 6 . 2-4, 8 . 44 AML. 9 .. 2011 1 PubMed 2014 12 31 . 225 6 . 1 7 . 1 acute myeloid leukemia OR acute myelogenous leukemia OR acute myeloblastic leukemia 12,230 . 2 1. chemotherapy 5,022 . 3 2. induction 1,456 . 4 3. children OR childhood OR pediatric 225 .. 1 Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents : recommendations from an international expert panel. Blood 2012 ; 120 : 3187-205. 2 Gibson BE, Webb DK, Howman AJ, et al ; United Kingdom Childhood Leukaemia Working Group and the Dutch Childhood Oncology Group. Results of a randomized trial in children with acute Myeloid Leukaemia : medical research council AML12 trial. Br J Haematol 2011 ; 155 : 366-76. 3 Creutzig U, Zimmermann M, Bourquin JP, et al.

6 Randomized trial comparing liposomal daunoru- bicin with idarubicin as induction for pediatric acute myeloid leukemia : results from Study AML-BFM 2004. Blood 2013 ; 122 : 37-43. 4 Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia : results of the AML02 multicentre trial. Lancet Oncol 11 : 543-52, 2010. 5 Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leuke- mia who benefit from the addition of gemtuzumab ozogamicin : results of the MRC AML15 trial. J Clin Oncol 2011 ; 29 : 369-77. 6 Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with De Novo acute myeloid leukemia improves event-free survival by reducing relapse risk : results from the randomized phase III Children's Oncology Group trial AAML0531.

7 J Clin Oncol 2014 ; 32 : 3021-32. 7 Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia . N Engl J Med 2009 ; 361 : 1249-59. 8 Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia : the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol 2009 ; 27 : 4007-13. 9 Tomizawa D, Tawa A, Watanabe T, et al. Appropriate dose reduction in induction therapy is es- sential for the treatment of infants with acute myeloid leukemia : a report from the Japanese Pe- diatric leukemia /Lymphoma Study Group. Int J Hematol 2013 ; 98 : 578-88. CQ3 45. CQ3. AML 2.. AML . AML .. stem cell transplantation SCT .. 1A.. AML . 2 5 . SCT 1 4 . 2 1990 . 8;21 . t inv 16 . core binding factor CBF -AML.

8 3-8 AML-05 AML99 . CCLSG9805 event free survival EFS . 50 60 overall survival OS 60 70 8-10 AML . LAME 89/91 . disease free survival DFS OS . 11, 12 AML . 2 6 . 2, 7 .. 2011 6 PubMed 2014 12 31 . 844 4 . 1 5 . 1 acute myeloid leukemia OR acute myelogenous leukemia OR acute myeloblastic leukemia 12,230 . 2 1. chemotherapy 5,022 . 46 AML. 3 2. children OR childhood OR pediatric 844 .. 1 Creutzig U, van den Heuvel-Eibrink MM, Gibson B, et al. Diagnosis and management of acute myeloid leukemia in children and adolescents : recommendations from an international expert panel. Blood 2012 ; 120 : 3187-205. 2 Gibson BE, Webb DK, Howman AJ, et al. Results of a randomized trial in children with acute myeloid leukaemia : Medical Research Council AML 12 trial. Br J Haematol 2011 ; 155 : 366-76. 3 Bloomfield CD, Lawrence D, Byrd JC, et al. Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype.

9 Cancer Res 1998 ; 58 : 4173-9. 4 Byrd JC, Dodge RK, Carroll A, et al. Patients with 8t ; 21 q22 ; q22 and acute myeloid leuke- mia have superior failure-free and overall survival when repetitive cycles of high-dose cytarabi- ne are administered. J Clin Oncol 1999 ; 17 : 3767-75. 5 Byrd JC, Ruppert AS, Mr zek K, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv 16 p13q22 or 16t ; 16 . p13 ; q22 : results from CALGB. 8461. J Clin Oncol 2004 ; 22 : 1087-94. 6 Creutzig U, Zimmermann M, Bourquin JP, et al. Second induction with high-dose cytarabine and mitoxantrone : different impact on pediatric AML patients with 8t ; 21 and with inv 16 .Blood 2011 ; 118 : 5409-15. 7 Rubnitz JE, Inaba H, Dahl G, et al. Minimal residual disease-directed therapy for childhood acute myeloid leukaemia : results of the AML02 multicentre trial.

10 Lancet Oncol 2010 ; 11 : 543-52. 8 Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia : The AML trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol 2009 ; 27 : 4007-13. 9 Tomizawa D, Tawa A, Watanabe T, et al. Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children. leukemia 2013 ; 27 : 2413-6. 10 CCLSG AML9805 . 2003 ; 17 : 346-51. 11 Perel Y, Auvrignon A, Leblanc T, et al. Treatment of childhood acute myeloblastic leukemia : dose intensification improves outcome and maintenance therapy is of no benefit multicenter studies of the French LAME Leuc mie Aigu My loblastique Enfant Cooperative Group. Leu- kemia 2005 ; 19 : 2082-9.