This document discusses acute myeloid leukemia (AML), including its causes, pathogenesis, diagnosis, risk stratification, treatment options, and key messages. AML is a neoplastic disease characterized by infiltration of blood, bone marrow, and other tissues by proliferative, clonal myeloid cells. Risk factors include hereditary conditions, radiation/chemical exposure, and certain drugs. Treatment is chosen based on risk assessment and may include intensive or non-intensive chemotherapy, hematopoietic stem cell transplantation, supportive care, or clinical trials. The document emphasizes tailoring treatment to individual risk profiles and age.

1. Dr ANKUR NANDAN VARSHNEY
Senior Resident
Department of Medical Oncology
Safdurjung Hospital

2. Acute Myeloid Leukemia
 neoplastic disease characterized by infiltration of the
blood, bone marrow, and other tissues by proliferative,
clonal undifferentiated cells of the hematopoietic
system.
 incidence increases with age, median age at diagnosis
is 67 years.

3. Etiology
 Hereditary: Down’s Syndrome
 Defective DNA repair, e.g., Fanconi anemia,
 Bloom Syndrome
 Ataxia telangectasia
 Radiation
 Chemical: Chemical , Plastic , Rubber, Petroleum
 Drugs: Alkylating agents (4–6 years after exposure, aberrations in
chromosomes 5 and 7).
 Topoisomerase II (1–3 years after exposure, involving
chromosome 11q23).
 Chloramphenicol, phenylbutazone, chloroquine and
methoxypsoralen

4. Pathogenesis
 AML is a result of distinct but co-operating genetic
mutations resulting in
 Proliferative & survival advantage to the myeloid
precursor cells
 Impaired differentiation & apoptosis of myeloid
precursor cells
Rubnitz JE et al. Hematol Oncol Clin N Am 24 (2010) 35–63

5. Pathogenesis
 Proliferative & survival advantage to the myeloid
precursor cells
FLT3, ALM, oncogenic Ras mutations
BCR/ABL and TEL/PDGFbR gene fusions
 Impair differentiation & apoptosis of myeloid
precursor cells
Mutations in CEBPA, CBF, HOX family members,
CBP/P300, and co-activators of TIF1
AML/ETO and PML/RARa fusions
Rubnitz JE et al. Hematol Oncol Clin N Am 24 (2010) 35–63

6. Clinical presentation
Signs & symptoms due to pancytopenia
Pallor, fatigue due to anemia
Fever & infections due to neutropenia
Bleeding due to thrombocytopenia
Infiltration of extramedullary sites
Lymphadenopathy
Hepatosplenomegaly
Granulocytic sarcoma
Leukemia cutis
Testicular involvement
Disseminated Intravascular Coagulation

7. Diagnostic evaluation
 Diagnosed by bone marrow examination.
 The standard test battery for bone marrow samples
currently includes
 cytomorphological and cytochemical studies
 flow cytometry
 cytogenetic analysis
 molecular studies for the detection of mutations that
affect prognosis, including Flt3 and nucleophosmin
mutations

8. Diagnosis

9. WHO classification
 Blast cutoff for a diagnosis of AML is 20% in the WHO
classification and 30% in the FAB.
 Specific chromosomal rearrangements, i.e.,
1. t(8;21)(q22;q22),
2. inv(16)(p13.1q22),
3. t(16;16)(p13.1;q22)
4. t(15;17)(q22;q12),
define AML even with <20% blasts.

10.  AML with recurrent Cytogenetic abnormality.
 AML with myelodysplasia related changes
 AML, therapy related
 Myeloid Sarcoma
 Myeloid Proliferation associated with down Syndrome
 Blastic plasmacytoid dendritic cell neoplasm
 AML, not otherwise specified

11. Risk Stratification

12. Cytogenetic and molecular genetic
risk classification

13. Patients > 60 years age
 Poor Outcome
 Disease Related
1. Favorable CBF translocations decreases
2. Unfavorable karyotypes and mutation decreases
3. Secondary AML increases
4. Increased multidrug resistance protein
 Patient related
1. Significant co-morbidities
2. Increased treatment related mortality

14. Age < 60 years

15.  High dose daunorubicin ( 90 mg/m2)
1. Favorable and intermediate risk cytogenetics
2. Younger < 50 years
 No significance difference with Idarubicin
 Some studies quote lower remission failure rate but no
over all survival

16.  Addition of Cladribine (DAC) was beneficial in
1. High risk Karotype
2. WBC count > 50,000
3. < 50 years.
 HIDAC was beneficial in
1. High-risk cytogenetic abnormalities
2. FLT 3- ITD
3. Secondary AML
4. Age < 45 years

19. Post Induction Therapy

21. Consolidation/ Post Remission

22. Patients > 60 years age
 Poor Outcome
 Disease Related
1. Favorable CBF translocations decreases
2. Unfavorable karyotypes and mutation decreases
3. Secondary AML increases
4. Increased multidrug resistance protein
 Patient related
1. Significant co-morbidities
2. Increased treatment related mortality

24.  HOVON study
 Escalated dose daunorubicin increased OS in patients < 65
years of age and CBF translocation
 ALFA study
 Standard idarubicin has better cure rates than High dose
daunorubicin in patients < 65 years. (p <0.49)
 No significant in patients > 65 years
 Gemtuzumab ozogamicin produces conflicting results. Not
approved.

25.  Clofarabine can be used in patients unfit for intensive
therapy but not FDA approved ( approved in relapsed
ALL) as monotherapy. Phase 3 trial undergoing
 Decitabine and Azacytidine ( approved for MDS) are
not approved By USFDA but approved in european
countries. Increased incidences of cytopenias
 Low dose cytarabine ( 20mg sc BD X 10 days)

26. Non-chemotherapy Agents
 Lenalidomide
 Also active in patients with prior MDS
 Phase I/II studies

27. Post-induction Therapy

28. Post- Remission Therapy

29.  Allogeneic HSCT was associated with a lower risk of
relapse and superior OS relative to autologous HSCT.
 Myeloablative HSCT did not provide survival benefit
in first CR due to increased incidence of non-relapse
mortality.
 Reduced Intensity conditioning is preferred in patients
> 60 years of age and an available donor.
1. As post remission therapy after CR
2. Treatment of induction failure in patients with low
volume disease.

30. Surveillance
 Complete Blood Counts and peripheral film X 1-3
monthly X 2 years
 3-6 monthly X 5 years
 Bone marrow is done
1. Persistent Cytopenias
2. Abnormal peripheral Smears

31. MRD
 Not recommended
 Flow cytometry has sensitivity of 1 in 10000 while
RTPCR has sensitivity of 1 in 1000.
 Lack of standardization
 Widely used in APL

32. Relapse

33. Relapsed Disease

35. Supportive Care

37. CNS manifestations

38. Key Messages
 Treatment is chosen on the basis of risk factors that
are easy to assess, which are derived from
 Standard diagnostic evaluation
 Specific prognostic scores
 Geriatric assessment.
 Selected older patients are suitable candidates for
intensive chemotherapy of the same type offered to
younger patients, possibly including HSCT with
reduced-dose conditioning treatment

39.  Patients who are not candidates for intensive
chemotherapy can be treated non-intensively with
chemotherapeutic drugs such as azaciti dine or low-
dose cytarabine
 Patients who are not suitable candidates for intensive
chemotherapy with bone marrow blast ≥30% can be
given
 purely supportive care
 Participation in a therapeutic trial
Key Messages