Acute Leukemia. Sebastian Giebel. Geneva 03/04/
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1 Acute Leukemia (including ALL) Sebastian Giebel Geneva 03/04/2012
2 Acute leukemias: EBMT survey 2
3 AML: EBMT survey Gratwohl A, et al. Bone Marrow Transplant
4 Acute leukemias: INCIDENCE Dores GM, Blood
5 Acute leukemias: PATHOGENESIS 5
6 Acute leukemias: DIAGNOSIS AML ALL Atlas of Hematology, Nagoya University School of Medicine Department of Medicine The Branch Hospital, Takuji Ichihashi, December 1996 Bone marrow cytology: >20% blasts Peripheral blood: anemia, neutropenia, thromboctopenia Organ lesions: spleen, lymph nodes, liver, mediastinum, CNS 6
7 Acute leukemias: DIAGNOSIS Diagnostic methods to establish type and subtype of acute leukemia, and risk subgroup: Cytology of bood/bone marrow Immunophenotyping (detection of specific markers of leukemic cells with the use of flow cytometry) Cytogenetics (detection of chromosomal abnormalities) Molecular genetics (detection of gene mutations, sometimes corresponding with chromosomal abnormalities) Acute Lukemia (including ALL) 7
8 Acute leukemias: DIAGNOSIS Acute Lukemia (including ALL) 8
9 Acute leukemias: DIAGNOSIS Immunophenotyping: Subtypes of ALL 9
10 Acute leukemias: DIAGNOSIS Cytogenetics: detection of chromosomal abnormalities Spanish National Cancer Research Center Acute Lukemia (including ALL) 10
11 Acute leukemias: DIAGNOSIS Genetic diversity of AML Dohner H, et al. Blood 2010 Acute Lukemia (including ALL) 11
12 Acute leukemias: DIAGNOSIS Genetic diversity of ALL Faderi S, et al., Cancer 2003 Acute Lukemia (including ALL) 12
13 Acute leukemias: DIAGNOSIS Cytogenetics: classification of AML and ALL t(8;21)(q22;q22) = AML1/ETO Sakai C, Internal Medicine
14 Acute leukemias: DIAGNOSIS Cytogenetics: classification of AML 14
15 Acute leukemias: DIAGNOSIS Cytogenetics: classification of ALL 15
16 Acute leukemias: DIAGNOSIS 16
17 Acute leukemias: PROGNOSTIC FACTORS Cytogenetic and molecular markers Complex karyotype De Souza Fernandez T, Brazilian J Genetics
18 AML: PROGNOSTIC FACTORS Risk group Subsets Favorable t(8;21)(q22;q22); RUNX1-RUNX1T1(AML1-ETO) inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 Mutated NPM1 without FLT3-ITD (normal karyotype) Mutated CEBPA (normal karyotype) Intermediate-I Mutated NPM1 and FLT3-ITD (normal karyotype) Wild-type NPM1 and FLT3-ITD (normal karyotype) Wild-type NPM1 and FLT3 (normal karyotype) Intermediate-II t(9;11)(p22;q23); MLLT3-MLL Cytogenetic abnormalities not classified as favorable or adverse Adverse inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 t(6;9)(p23;q34); DEK-NUP214(CAN) t(v;11)(v;q23); MLL rearranged -5 or del(5q); -7; 17p abnormalities; complex karyotype Dohner H, et al. Blood
19 AML: PROGNOSTIC FACTORS AML: Survival according to genetically defined risk groups Rollig C, J Clin Oncol
20 AML: PROGNOSTIC FACTORS AML: Survival after allohsct according to genetically defined risk groups Armand P, Biol Blood Marrow Transplant
21 ALL: PROGNOSTIC FACTORS ALL: Survival according to the presence of Ph chromosome i.e. t(9;22) or BCR/ABL Goldstone AH, Blood
22 Acute leukemias: PROGNOSTIC FACTORS 22
23 Acute leukemias: PROGNOSTIC FACTORS 23
24 Acute leukemias: PROGNOSTIC FACTORS 24
25 Acute leukemias: TREATMENT AML/ALL INDUCTION CR CONSOLIDATION High risk DONOR+ Standard risk DONOR- ALLO-HSCT AUTO-HSCT Maintenance CHT Observation 25
26 AML: INDICATIONS FOR ALLO-HSCT 1 st COMPLETE REMISSION Sibling MUD GIMEMA HR, IR HR, IR-MRD(+) NILG UK HR, IR Fl3-ITD.(+), MLL(+), WBC >50, long time to CR, M0M6M7, hepatosplenomegaly, Sec/MDS Poor risk calculated based on: age, sex, status post Ind1, cytogenetics, WBC, SecAML PETHEMA HR, IR HR PALG HR, IR HR, IR Primary induction failure Relapse, after salvage cht. ALWP EBMT Educational Symposium, Milan 2010, By courtesy of Fabio Ciceri 26
27 Acute leukemias: TREATMENT DGN PRETREATMENT: PDN PALG ALL6 Ph(-) INDUCTION I: DNR/VCR/PEGAsp/PDN CR, MRD-I <0.1% CR, MRD-I 0.1%; NR <40 y 40y, CD52(-) >40 y, CD52(+) MRD-I INDUCTION II: FLAM INDUCTION II: MiniFLAM INDUCTION II: FLAM-CAMP MRD-II 40 y <40 y CR NR CONSOLIDATION I: ID-Mtx/Vep/Dexa CONSOLIDATION I: HD-Mtx/Vep/Dexa Experimental therapy MRD-III CONSOLIDATION II: Cy/HD-AraC/PEGAsp MRD-IV MRD-I 0.1% and/or MRD-III,IV 0.05% MRD-I <0.1% and MRD-III,IV <0.05% Donor(+) Donor(-) CONSOLIDATION III: ID- or HD-Mtx/Vep/Dexa MRD-V Sib/MUD-alloHSCT CONSOLIDATION III: FLAM lub HyperCVAD AutoHSCT MAINTENANCE: 8xMP/Mtx/DNR/VCR/PDN 8xMP/Mtx/DNR/PDN AutoHSCT MAINTENANCE: 12xMP/Mtx 27
28 Acute leukemias: DIAGNOSIS Response to therapy: Complete remission normal blood count, <5% blasts in bone marrow, no organ lesions Cytogenetic remission disappearance of chromosomal abnormalities present at diagnosis Molecular remission - disappearance of gene mutations present at diagnosis Acute Lukemia (including ALL) 28
29 Acute leukemias: TREATMENT 29
30 Acute leukemias: DISEASE HISTORY 30
31 Acute leukemias: DISEASE STATUS AT AUTOLOGOUS CELL COLLECTION 31
32 Acute leukemias: DISEASE STATUS AT STEM CELL COLLECTION/TRANSPLANTATION 32
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