7/28/2019 5.26 Davis-Hovda. ALL

1/22

Acute

LymphoblasticLeukemia

Maggie Davis Hovda5/26/2009

7/28/2019 5.26 Davis-Hovda. ALL

2/22

7/28/2019 5.26 Davis-Hovda. ALL

3/22

7/28/2019 5.26 Davis-Hovda. ALL

4/22

Epidemiology

Most common childhood acute leukemia,

~80%

Incidence in adults ~20%

Bimodal distribution of occurrence:

Peak at age 2-5

Second increased incidence after age 50

7/28/2019 5.26 Davis-Hovda. ALL

5/22

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

7/28/2019 5.26 Davis-Hovda. ALL

6/22

Mechanisms of Leukemia Induction

1Activation of a proto-oncogene OR creation of

a fusion gene with

oncogenic properties

- Ph Chromosome t(9;22)

2 Loss or inactivation

of 1 tumor

suppressor gene

- p53 (p16 mutation)

7/28/2019 5.26 Davis-Hovda. ALL

7/22

Etiology

Unknown

? Genetic Predisposition Increased incidence amongst monozygotic and dizygotic twins

Down Syndrome

Disorder with chromosomal fragility: Fanconis anemia

Bloom Syndrome

Ataxia-Telangiectasia

? Infections

HTLV1 in T cell leukemia/lymphoma EBV in mature B cell ALL

HIV in lymphoproliferative DO

7/28/2019 5.26 Davis-Hovda. ALL

8/22

Presentation

Nonspecific Symptoms Fatigue/decreased energy

Fever

Easy bruising

Bleeding

Dyspnea

Dizziness

Infection

Joint, extremity pains

CNS involvement

7/28/2019 5.26 Davis-Hovda. ALL

9/22

Clinical Presentation

Physical Exam

Pallor

Ecchymoses Petechiae

LAD

Hepatosplenomegaly

Lab Abnormalities

anemia

wbc vary 0.1 (20-40%) - >100 k

(10-16%)

Platelets usually

LD, uric acid

CXR: eval for thymic mass

CSF to eval for

involvement

7/28/2019 5.26 Davis-Hovda. ALL

10/22

7/28/2019 5.26 Davis-Hovda. ALL

11/22

Immunophenotyping

From: Jabbour, E. et al. Adult Acute LymphoblasticLeukemia. Mayo Clinic Proc. 2005;80(11):1517-1527

7/28/2019 5.26 Davis-Hovda. ALL

12/22

7/28/2019 5.26 Davis-Hovda. ALL

13/22

Cytogenetic Abnormalities

From: Jabbour, E. et al. Adult Acute LymphoblasticLeukemia. Mayo Clinic Proc. 2005;80(11):1517-1527

7/28/2019 5.26 Davis-Hovda. ALL

14/22

Classification of ALL

Immunologic

Subtype

% of cases FAB Subtype Cytogenetic

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: Harrisons Principles of Internal Medicine, 16thed. 2005. Chapter 97, Malignancies of lymphoid cells.

7/28/2019 5.26 Davis-Hovda. ALL

15/22

Differential Diagnosis

ITP

Aplastic Anemia

Infectious mononucleosis

Rheumatoid Arthritis

Rheumatic Fever Collagen Vascular Disease

7/28/2019 5.26 Davis-Hovda. ALL

16/22

Treatment

1 Remission Induction

2 Intensification (Consolidation) Therapy

3 Maintenance Therapy

4 CNS Prophylaxis

5 Allogeneic Stem Cell Transplant

7/28/2019 5.26 Davis-Hovda. ALL

17/22

Treatment

Remission InductionGoals: 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

IntensificationHigh doses of multiple agents not used during

induction or re-administration of the induction regimen

7/28/2019 5.26 Davis-Hovda. ALL

18/22

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

7/28/2019 5.26 Davis-Hovda. ALL

19/22

Treatment

Stem Cell Transplant

Done during first CR

Indications: Ph Chromosome

t(4;11) mutation

Poor initial response to induction therapy

OtherAdolescents benefit significantly from pediatric ALL

regimens vs. adult regimens

7/28/2019 5.26 Davis-Hovda. ALL

20/22

Relapse & Prognosis

RelapseMost 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

7/28/2019 5.26 Davis-Hovda. ALL

21/22

Prognosis

Overall better in children than in adults

In adults, worse outcomes with:

Increasing age, >60

Increased wbc count at presentation

7/28/2019 5.26 Davis-Hovda. ALL

22/22

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.

Harrisons Principles of Internal Medicine, 16th ed. 2005.

Chapter 97, Malignancies of lymphoid cells.