Acute

Lymphoblastic
Leukemia
Maggie Davis Hovda
5/26/2009
Definition
 Neoplastic disease which results from a
mutation in a single lymphoid progenitor
cell at one of several discrete stages of
development
 B Cell or T Cell
Epidemiology
 Most common childhood acute leukemia,
~80%
 Incidence in adults ~20%
 Bimodal distribution of occurrence:
 Peakat age 2-5
 Second increased incidence after age 50
Pathogenesis
 Acquired Genetic Change in Chromosome
 Change in number, ie ploidy
 Change in structure
 Translocations (most common)
 Inversions
 Deletions
 Point mutations
 Amplifications
Changes in normal means of cell differentiation, proliferation, and
survival
Mechanisms of Leukemia Induction

 1 – Activation of a proto- 2 – Loss or inactivation

oncogene OR creation of of ≥ 1 tumor
a fusion gene with suppressor gene
oncogenic properties - p53 (p16 mutation)
- Ph Chromosome t(9;22)
Etiology
 Unknown
 ? Genetic Predisposition
 Increased incidence amongst monozygotic and dizygotic twins
 Down Syndrome
 Disorder with chromosomal fragility:
 Fanconi’s anemia
 Bloom Syndrome
 Ataxia-Telangiectasia
 ? Infections
 HTLV1 in T cell leukemia/lymphoma
 EBV in mature B cell ALL
 HIV in lymphoproliferative DO
Presentation
 Nonspecific Symptoms
 Fatigue/decreased energy
 Fever
 Easy bruising
 Bleeding
 Dyspnea
 Dizziness
 Infection
 Joint, extremity pains
 CNS involvement
Clinical Presentation
 Physical Exam  Lab Abnormalities
 Pallor  anemia
 Ecchymoses  wbc vary
 Petechiae  0.1 (20-40%) - >100 k
(10-16%)
 LAD
 Platelets – usually ↓
 Hepatosplenomegaly  ↑ LD, uric acid
 CXR: eval for thymic mass
 CSF to eval for
involvement
Diagnosis

 Morphologic
 French American British Classification
 L1: small uniform blasts (pediatric ALL)
 L2: larger, more variable sized blasts (adult ALL)

 L3: uniform cells with basophilic and sometimes

vacuolated cytoplasm (mature B cell ALL)
Immunophenotyping

From: Jabbour, E. et al. Adult Acute Lymphoblastic

Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527
Cytogenetic Abnormalities

From: Jabbour, E. et al. Adult Acute Lymphoblastic

Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527
 Classification of ALL
Immunologic % of cases FAB Subtype Cytogenetic
Subtype Abnormalities

Pre-B ALL 75 L1, L2 t(9;22), t(4;11),

t(1;19)

T cell ALL 20 L1, L2 14q11 or 7q34

B cell ALL 5 L3 t(8;14), t(8;22),

t(2;8)

From: Harrison’s Principles of Internal Medicine, 16th

ed. 2005. Chapter 97, Malignancies of lymphoid cells.
Differential Diagnosis
 ITP
 Aplastic Anemia
 Infectious mononucleosis
 Rheumatoid Arthritis
 Rheumatic Fever
 Collagen Vascular Disease
Treatment
 1 – Remission Induction
 2 – Intensification (Consolidation) Therapy
 3 – Maintenance Therapy
 4 – CNS Prophylaxis
 5 – Allogeneic Stem Cell Transplant
Treatment
 Remission Induction
 Goals: restore normal hematopoiesis, induce a
complete remission rapidly in order to prevent
resistance to drugs
 Standard induction regimen
 4 or 5 drugs: vincristine, prednisone, anthracycline, L-
asparaginase, +/- cyclophosphamide
 Intensification
 High doses of multiple agents not used during
induction or re-administration of the induction regimen
Treatment
 Maintenance Therapy
 Daily po 6MP, weekly MTX, monthly pulses of
vincristine and prednisone for 2-3 yrs
 CNS Prophylaxis
 Given during induction and intensification
 Intrathecal: MTX, Cytarabine, corticosteroids
 Systemic: high dose mtx, cytarabine, L-asparaginase
 +/- Cranial Irradiation
Treatment
 Stem Cell Transplant
 Done during first CR
 Indications:
 Ph Chromosome
 t(4;11) mutation
 Poor initial response to induction therapy
 Other
 Adolescents benefit significantly from pediatric ALL
regimens vs. adult regimens
Relapse & Prognosis
 Relapse
 Most occur during treatment or within the first 2 years
 Bone Marrow is the most common site
 Poor prognostic factors in patients previously treated:
 Relapse on therapy
 Short initial remission after intense therapy
 T-cell immunophenotype
 Ph Chromosome
 Circulating blasts
 High leukocyte count at relapse
Prognosis
 Overall better in children than in adults
 In adults, worse outcomes with:
 Increasingage, >60
 Increased wbc count at presentation
Sources
 Jabbour, E. et al. Adult Acute Lymphoblastic Leukemia.
Mayo Clinic Proc. 2005;80(11):1517-1527
 Xavier, T. Chemotherapy of acute leukemia in adults.
Expert Opin. Pharmacother. (2009) 10(2):221-237
 Williams Hematology, 6th ed. 2001. Chapter 97, Acute
Lymphoblastic Leukemia.
 Harrison’s Principles of Internal Medicine, 16th ed. 2005.
Chapter 97, Malignancies of lymphoid cells.