presentation by Dr.Safwan Moideen ,Intern,Department of general medicine,Azeezia medical college,Kollam,Kerala

1. ACUTE LYMPHOBLASTIC LEUKEMIA
Dr.Safwan Moideen
House surgeon
General Medicine
Azeezia medical college

2. DEPARTMENT OF GENERAL MEDICINE
AZEEZIA MEDICAL COLLEGE,KOLLAM

3. • In acute lymphoblastic leukemia (ALL), the
malignant clone arises from hematopoietic
progenitors in the bone marrow or lymphatic
system resulting in an increase of immature
nonfunctioning leukemic cells.

4. INCIDENCE AND AGE
• Most frequent neoplastic disease in children
with an early peak at the age of 3–4 years
• Incidence in adults is higher in younger adults
(1–1.5/100000 for the age group 15–24 years)
and decreasing thereafter, only to increase
again in elderly people to 2.3 for age >65 years

5. Immunological subtypes
B-Cell Lineage
• More than 70% of adult ALLs are of B-cell origin and the most
frequent immunological subtype, common ALL, is characterized by
the presence of ALL antigen, a glycoprotein (gp100/CD10).
• Common ALL blast cells do not carry markers of mature B cells
such as cytoplasmic immunoglobulins or surface membrane
immunoglobulins
• Pre-B-ALL (early B-ALL) is characterized by the expression of
cytoplasmic immunoglobulin, being negative in common ALL but is
otherwise identical with all other cell markers.

6. T-cell Lineage
• Approximately 25% of adult ALL belongs to
the T-cell lineage.
• All cases express the T-cell antigen (gp40,
CD7) and cytoplasmatic or surface CD3

7. Biphenotypic or Mixed Leukemias
• Defined as those in which markers of lymphoid
and myeloid lineages are coexpressed on the
same leukemic cells without the typical
phenotype of either ALL or AML.
• Bilineage leukemias are those with two
populations of blast cells with either lymphoid or
myeloid antigens

8. ETIOLOGY
• Unknown etiology
• Ataxia telangiectasia
• Bloom syndrome
• Benzene exposure
• Chemotherapy
• Down syndrome
• Ionizing radiation
• HTLV-1 infection ( Human T lyphotropic virus )
• Fanconi anemia
• Klinefelter syndrome
• Neurofibromatosis
• Philadelphia Chromosome – t(9:22)

9. CLINICAL FEATURES
• Hb decrease Pallor + , fatigue
• Platelet decrease Bleeding
• Granulocytopenia Infections : recurrent
pneumonia, necrotizing fasciitis
• Bone pain
• Leukemic infiltration
Hepatospleenomegaly, Lymphadenoapthy
• CNS leukemia ( meningeosis leukemica)

10. WORK UP
1. Complete blood count
• Decrease in Hb
• TC – normal / increased
• Platelet- Decreased

11. 2. Bone marrow aspiration
• Investigation of choice
• Site : Post. Superior iliac spine
• Findings :
A) Blast > 20% ( WHO criteria ) , >30% ( FAB criteria )
B) Morphology
- L1 ( most common )
- L2
- L3

12. • Immunophenotyping
To identify cell type, most commonly cancer
cells present express CD10/CD19 ( used for
targeted therapy )
• Cytogenetics
FISH technique
To identify chromosomal abdnormalities

13. • Cytochemistry
To check for presence of TDT positivity
(terminal deoxynucleotide transferase ),
Nucleus of the particular cell contains a DNA
polymerase which is responsible for
uncontrolled mitosis

14. 3.Lumbar puncture
• To diagnose CNS leukemia
• Procedure is restricted to patients with an adequate
platelet count (>20 × 109/L), an absence of manifest
clinical hemorrhage, and without a high white blood
cell count.
• Intrathecal methotrexate given before LP , to prevent
iatrogenic CNS leukemia
• During the process of LP , it could cause inoculation of
CSF of patient with cancer cells as the needle go via a
blood vessel and cause iatrogenic cns leukemia

15. • Baseline Uric acid, phosphate, calcium,
potassium to identify tumor lysis syndrome
after chemotherapy

16. HIGH RISK ALL LOW RISK ALL STANDARD RISK
Age <1 yr , >10yr Age 1-9 yr Age 1-9yr
Males have poor prognosis Female
Dissemination-
Lymphadenopathy , HSM,
CNS
Higher the WBC count Wbc count < 50,000 Wbc < 50K
Matue B cell ALL
Hypoploidy
Pre-B cell ALL
Hyperdiploidy
Pre-B cell ALL
Hyperdiploidy
Absence of CD10
Presence of MLL gene
Chromosomal
abnormalities
t(9:22)(8:14)(1:19)(4:11)
T(12:21)
Normal cytogenetics
Treatment – Stem cell
Transplantion
Treatment –
Chemotherapy
Treatment- Chemotherapy

17. Very High risk ALL
Induction failure , t(9:22)
Treatment – TKI, targeted therapy

18. TREATMENT
• Objective : To achieve complete molecular
remission
• Able to achieve as early as 6 to 16 weeks of
initiating chemotherapy
• High risk patients- Complete molecular
remission in 80% cases in this time frame
• Standard risk patients- Complete molecular
remission in 90% cases in this time frame

19. Complete molecular remission Minimal residual
disease ( MRD )
• <0.01% cancer cells left behind
• <1 live leukemic blast cell identified per every
10,000 cells
Methods of MRD
Real time quantitative PCR
Flow cytometry
FISH ( Fluorescence insitu hybridization )

21. Adult B cell ALL
• 25% are Ph +
Treatment
• Tyrosine kinase inhibitors
-Imatinib, Dasatinib
• Immunological targeting
- Blinatumomab ( Monoclonal antibody)
-CART-19 – chimeric antigen receptor T
cells

22. Chimeric Antigen Receptor (CAR) T
cells
• T cells engineered to kill leukemic cells1
• CAR T-cell therapy can be highly toxic as the
accompanying cytokine release syndrome
related to systemic immune activation produces
fever, hypotension, confusion and delirium.
• These effects appear in the first week of therapy
and generally abate, but severe neurotoxicity may
be slow to recover.

24. Chemotherapy for ALL
Remission induction 1
• Vincristine
• L-asparaginase
• Prednisolone
• Daunorubicin
• Intrathecal Methotrexate

25. Remission induction 2
• Methotrexate
• Cranial irradiation
• Cyclophosphamide
• 6 mercapto purine

26. Consolidation ( 14-28 weeks )
• Vincristine
• Daunorubicin
• Cyclophosphamide
• Cystosine Arabinoside

27. Maintenance ( 2-2.5 years )
• Vincristine
• Daunorubicin
• L-asparaginase
• Prednisolone
• 6 MP

28. THERAPY OF CNS DISEASE
• About 5–10% of adult patients present with
manifestations of CNS leukemia
• Intrathecal MTX alone or in combination with cytosine
arabinoside or hydrocortisone
• The intrathecal therapy is given 2–3 times per week,
continued for >2 or 3 weeks until two consecutive CSF
examinations show no evidence of leukemic infiltration

29. CONCLUSION
• Treatment outcome of adult ALL has improved
with about half of the patients surviving >5 years
and those surviving 5 years are most likely cured.
• Newer options, such as less intensive
chemotherapy, reduction of stem cell
transplantation, and incorporation of targeted
therapies are promising options to reduce
toxicities and improve the life quality.

30. Thank you…