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Acute lymphoblstic leukemia (ALL) PowerPoint Presentation

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Published on : Feb 24, 2014
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Acute lymphoblastic leukemia (ALL) Clonal proliferation and accumulation of blast cells in blood, bone marrow and other organs Disorder arises from a single lymphoid progenitor cell that has undergone genetic damage leading to dysregulated growth and arrested differentation Heterogenous disease with different biological subtypes Incidence in adults : The overall incidence 1-1,5/100 000 20% of acute leukemias in adults Etiology - unknown

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Acute leukemias - clinical features 1. Bleeding 2. Fever/infection 3. Bone/joint pain 4. Hepatomegaly 5. Splenomegaly 6. Lymphadenopathy 7. CNS involvement

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Symptoms and signs Patients (%) Infection/fever 36 Hemorrhages 33 Lyphadenopathy 57 Splenomegaly 56 Hepatomegaly 47 Mediastinum mass 14 CNS infiltration 7 Other organ involvement 9 Pleura 2.9 Bone 1.2 Pericardium 1.0 Retina 1.0 Skin 0.6 Tonsils 0.6 Lung 0.5 Kidney 0.4 Testes 0.3

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Acute leukemias - laboratory findings (1) 1. Blood examination - anemia - thrombocytopenia - variable leukocyte count, usually increased - blood morphology: presence of blast cells 2. Bone marrow morphology - presence of blast cells - suppression of normal hematopoiesis

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Laboratory findings in patients with ALL at diagnosis Neutrophils (×106/L) Patients (%) <500 23 500-1000 14 1000-1500 9 >1500 54 Platelet (X 106/L) <25,000 30 25,000-50,000 22 50,000-150,000 33 >150,000 15 Hemoglobin (g/dL) <6 8 6-8 20 8-10 27 10-12 24 >12 21

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Laboratory findings in patients with ALL at diagnosis Patients (%) Leukocytes (×106/L) <5,000 27 5000-10,000 14 10,000-50,000 31 50,000-100,000 12 >100,000 16 Lymphoblasts in blood smear present 92 absent 8 Limphoblasts in bone marrow smear <50% 3 51%-90% 51 >90% 46 „empty” bone marrow aspiraation 16

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Acute leukemias - Laboratory findings (2) 3. Cytochemical stains 4. Immunophenotyping 5. Cytogenetics 6. Molecular studies

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Morphologic subtypes of acute lymphoblastic leukemias (FAB classification) Subtype Morphology Occurrence (%) L1 Small round blasts 75 clumped chromatin L2 Pleomorphic larger blasts 20 clefted nuclei, fine chromatin L3 Large blasts, nucleoli, 5 vacuolated cytoplasm

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Acute lymphoblastic leukemias - reactivity with special stains Subtype Peroxidase or Non-specific Periodic Sudan black esterase acid-Schiff L1 - - +++ L2 - - +++ L3 - - +++

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Immunologic classification of acute lymphoblastic leukemias B- lineage (80%) Markers Pro-B CD19(+),Tdt(+),CD10(-),CyIg(-), Common CD19(+),Tdt(+),CD10(+),CyIg(-), Pre-B CD19(+),Tdt(+),CD10(+),CyIg(+),SmIg(-) Mature-B CD19(+),Tdt(+),CD10(±),CyIg(±),SmIg(+) T-lineage (20%) Early-T cCD3(+) CD7(+), CD2(+/-), Tdt(+), Cortical-T cCD3(+) CD7(+), CD2(+), CD1a(+) CD4(+) CD8(+)Tdt(+) Mature-T sCD3(+) CD1a(-)

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Chromosomal/molecular abnormalities with prognostic significance in ALL Better prognosis - normal koryotype - hyperdiploidy Poor prognosis - t (8; 14) - t (4; 11) Very poor prognosis - t (9; 22); BCR/ABL (+)

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Risk classification in ALL 1. Standard risk 2. High risk 3. Very high risk

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High-risk ALL 1. Pre – T (cCD3+/CD7+/CD2+) 2. Pro – B (CD19+/TdT+/CD10-/cIgG-) 3. Age > 35 years, 4. -WBC > 30 G/L in B-ALL > 100 G/L in T-ALL 5. No remission after 4 weeks of induction therapy 6. Detection of MRD (minimal residual disease) with flow cytometry or molecular methods- MRD positivity 7. t(4;11)

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Very high-risk ALL Chromosome Philadelphia - positive or BCR/ABL (+)

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Treatment phases in ALL Remission induction therapy Post-remission treatment Intesification (consolidation) therapy Haematopoietic stem cell transplantation Maintance chemotherapy Prophylaxis / treatment of CNS involvement Treatment of refractory/relapsed ALL

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Treatment strategy in ALL

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The choice of treatment-strategy depends on: 1. Risk stratification 2. Immunophenotype of leukemic cells - T lineage, - early B lineage, - mature B lineage, 3.Age and biological condition 4. Goal of treatment

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Remission induction therapy in ALL Antineoplastic treatment Drugs: prednisone, vincristine, antracycline, asparginase, cytosine arabinoside, cyclophosphamide Imatinib in combination with chemotherapy in Ph+ ALL Treatment duration: 4-8 weeks 2. CNS prophylaxis: Mtx it, Ara-C it, steorids it 3. Supportive care 4. Treatment of complications

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The objective of induction chemotherapy = complete remission Definition of CR: Normocellular bone marrow with 5% or fewer blasts Peripheral blood without blasts Granulocyte count > 1,0 G/L, platelet count > 100G/L The absence of any signs and symptoms od extramedulary leukemia Complete remission: 80-90 % of pts

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Intensification therapy 8-12 weeks of chemotherapy high dose of (HD) cytosine arabinoside, HD methotrexate, HD cyclophosphamide, asparaginase, steroids CNS prophylaxis: Mtx it, Ara-C it, steroids it alternatively: radiotherapy 18 Gy

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Post-remission therapy in standard-risk ALL 1. Chemotherapy a/. Maintenance therapy: 6-mercaptopurine, methotrexate - for 2-3 years. b/. Intensification treatment periodically repeated: daunorubicin/adriablastin, prednisone, vincristine, cyclophosphamide. 2. CNS prophylaxis

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Post-remission therapy in high-risk ALL 1. Allogeneic hematopoietic stem cell transplantation - high-dose therapy - reduced intensity conditioning 2. Autologous HSCT (donor-) Conditioning regimen: TBI 12-13 Gy plus cyclophosphamide 120 mg/kg

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Post-remission therapy in very high-risk ALL - High-dose therapy ( reduced-intensity) + allogeneic stem cell transplantation Maintance therapy after alloHSCT: imatinib

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Treatment results in ALL Adults Complete remission (CR) 85-95% Leukemia-free survival (LFS) 40-60% Children Complete remission (CR) 95-99% Leukemia-free survival (LFS) 70-80%

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Treatment results LFS Chemotherapy 30-40% Auto-HSCT 40-45% Allo-HSCT 45-60%

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