Acute%20lymphoblastic%20leukemia%20(ALL) - PowerPoint PPT Presentation

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Acute%20lymphoblastic%20leukemia%20(ALL)

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methotrexate - for 2-3 years. b/. Intensification treatment periodically ... dose cytosine arabinoside, high dose methotrexate, high dose cyclophosphamide. ... – PowerPoint PPT presentation

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Title: Acute%20lymphoblastic%20leukemia%20(ALL)


1
Acute lymphoblastic leukemia (ALL)
  • Clonal proliferation and accumulation of blast
    cells in blood, bone marrow and other organs
  • Disorder originates in single B or T lymphocyte
    progenitor
  • Heterogenous disease with different biological
    subtypes
  • Incidence in adults 20 of acute leukemias
  • Etiology - unknown

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

3
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

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

5
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

6
Acute lymphoblastic leukemias - reactivity with
special stains
  • Subtype Peroxidase or Non-specific
    Periodic
  • Sudan black esterase
    acid-Schiff
  • L1 - -
  • L2 - -
  • L3 - -

7
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)
  • Pre-T CD7(), CD2(-), Tdt(),
  • Mature-T CD7(), CD2(), Tdt(),

8
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 ()

9
Risk classification in ALL
  • 1. Standard risk
  • 2. High risk
  • 3. Very high risk

10
High-risk ALL
  • 1. Pre - T
  • 2. Pro - B
  • 3. Age gt 35 years,
  • 4. WBC gt 30 G/L in B-ALL
  • gt 100 G/L in T-ALL
  • 5. No remission after 4 weeks of induction
  • therapy

11
Very high-risk ALL
  • Chromosome Philadelphia - positive or BCR/ABL ()

12
Treatment strategy in ALL
13
In ALL the choice of treatment-strategy depends
on
  • 1. Risk qualification
  • 2. Immunophenotype of leukemic cells
  • - T lineage,
  • - early B lineage,
  • - mature B lineage,
  • 3.Age and biological condition
  • 4. Goal of treatment

14
Remission induction therapy in ALL
  • 1. Antineoplastic treatment
  • a/Drugs prednisone, vincristine, asparginase,
    cyclophosphamide
  • duanorubicin/adriablastin/epirubicin,
  • cytosine arabinoside,
  • b/Treatment duration 4-8 weeks
  • c/ No of courses 1- 2
  • 2. CNS prophylaxis
  • 3. Supportive care
  • 4. Treatment of complications

15
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

16
Post-remission therapy in high-risk ALL
  • 1. Intensification treatment amsacrine,
    mitoxantrone, idarubicine, high dose cytosine
    arabinoside, high dose methotrexate, high dose
    cyclophosphamide.
  • 2. Hematopoietic stem cell transplantation
  • - high-dose therapy
  • - reduced intencity conditioning

17
Post-remission therapy in very high -risk ALL
  • - High-dose therapy ( reduced-intencity ?)
  • allogeneic stem cell transplantation

18
Treatment results in ALL
  • Adults
  • Complete remission (CR) 80-85
  • Leukemia-free survival (LFS) 30-40
  • Children
  • Complete remission (CR) 95-99
  • Leukemia-free survival (LFS) 70-80

19
AutoHSCT in ALL
  • Treatment related mortality (TRM) 2-8
  • CR1
  • LFS 42 (15-65)
  • RI ( relapse incidence) 51
  • CR2
  • LFS 24 (20-25)
  • RI 60

20
AlloHSCT in ALL
  • Sibling donor
  • CR1 gtCR2 relapsed/refractory
  • LFS 51 (21-80) 34 (13-42)
    20 (12-33)
  • RI 26 (9-50) 47 (40-69)
    71 (59-76)
  • TRM 29 (12-42)
  • Matched unrelated donor
  • LFS 39 (38-42)
  • RI 22 (19-23)
  • TRM 48
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