2. ACUTE LEUKEMIA
• Leukemia's are a group of disorders characterized by malignant
transformation and proliferation of hematopoietic stem cells .
• Acute leukemia's are characterized by defects in maturation of
leukocytes .
• Two types – acute myeloid leukemia and acute lymphoid leukemia.
4. INTRODUCTION
• AML consists of a group of relatively well-defined hematopoietic neoplasms
involving precursor cells committed to the myeloid line of cellular development
(those giving rise to granulocytic, monocyte, erythroid, or megakaryocytic
elements).
• It is characterized by blocked myeloid-lineage differentiation and accumulation of
myeloid blast cells in the bone-marrow that results in catastrophic bone-marrow
failure.
• Median age at diagnosis of 65 years.
5. ETIOLOGY
• Most cases of AML are idiopathic.
•Genetic predisposition
•Chemical/other occupational exposures (Exposure to
ionizing radiation, benzene, chloramphenicol,
phenylbutazone)
•Therapy-associated AML.
• Alkylating agents
•Topoisomerase II inhibitor
6. GENETIC PREDISPOSITION
• Myeloid neoplasms with germline predisposition represent an important and growing
subset of disease.
• Germline mutations associated with increased risk of developing a myeloid neoplasm
include CEBPA, DDX41, RUNX1, ANKRD26, ETV6, and GATA2
• Down syndrome with trisomy 21
• Fanconia anemia
• Bloom syndrome
• and ataxia-telangiectasia are associated with AML.
• Congenital neutropenia (Kostmann syndrome) may evolve into AML
7. CLASSIFICATION
• AML with recurrent genetic abnormalities
• AML with myelodysplasia-related features
• Therapy-related AML and MDS
• AML, not otherwise specified
• Myeloid sarcoma
• Myeloid proliferations related to Down syndrome
• Marrow (or blood) blast count of ≥20% is required to establish the diagnosis
of AML
• except for AML with the recurrent genetic abnormalities t(15;17), t(8;21),
inv(16), or t(16;16).
8. CLINICAL FEATURES
• Patients with AML usually present with nonspecific symptoms that are
the consequence of pancytopenia.
• Fatigue is a frequent first symptom among AML patients.
• Anorexia and weight loss are common.
• Fever with or without an identifiable infection is the initial symptom in
• ~10% of patients.
9. • Signs of abnormal hemostasis – bleeding and easy bruising .
On occasion bone pain , lymphadenopathy , nonspecific cough can
also be presenting features.
• Leukemic involvement (leukemia cutis or myeloid sarcoma).
• Sites involved are most commonly the skin, lymph node, bone,
periosteum gastrointestinal tract, soft tissue, and testis.
• Oral examination may show gingival hypertrophy, especially
in the monocyte oral candidiasis, or herpetic lesions
10. • Peripheral blood —
• Normocytic, normochromic anemia
• The reticulocyte count is normal or decreased.
• Thrombocytopenia -Both morphologic and functional platelet
abnormalities may be seen.
• The median presenting leukocyte count is ~15,000/μL
• Between 25 and 40% of patients have counts <5000/μL,
• 20% have counts >100,000/μL
11. • Myeloblasts -are immature cells with large nuclei, usually with prominent
nucleoli, and a variable amount of pale blue cytoplasm (sometimes with faint
granulation) after staining with Wright Giemsa.
• The nuclear to cytoplasmic ratio and morphology vary depending upon
the maturity of the cell.
• Auer rods, which are pathognomonic of myeloblasts, vary in frequency
depending upon the AML subtype.
• They can be identified as pink/red rod-like granular structures in the cytoplasm
12. • Morphology of acute
myeloid leukemia (AML) cells.
• A. Uniform population of
primitive myeloblasts with
immature chromatin, nucleoli
in some cells, and primary
cytoplasmic granules.
• B. Leukemic myeloblast
containing an Auer rod.
• C. Promyelocytic leukemia
cells with prominent
cytoplasmic primary granules.
• D. Peroxidase stain shows
dark blue color characteristic
of peroxidase in granules in
AML.
13. Pretreatment Evaluation
• Once the diagnosis of AML is suspected, thorough evaluation
and initiation of appropriate therapy should follow.
• In addition to clarifying the subtype of leukemia,
• Initial studies should evaluate the overall functional integrity of
the major organ systems, including the cardiovascular,
pulmonary, hepatic, and renal systems.
14. • Factors that have prognostic significance, either for achieving CR or for
predicting CR duration, should also be assessed before initiating treatment,
including cytogenetics and molecular markers.
• Leukemic cells should be obtained from all patients and cryopreserved for
future investigational testing as well as potential future use as new diagnostics
and therapeutics become available.
• All patients should be evaluated for infection.
15.
16.
17. • Treatment of the newly diagnosed patient with AML is divided into
two phases, induction and post remission management
(consolidation) .
• The initial goal is to induce CR.
The initial induction treatment and subsequent postremission therapy
are chosen based on
patient’s age,
overall fitness,
cytogenetic/molecular risk.
18. • Treatment recommendations for patients < 60y or for select patients
• ≤ 75y (good performance status, minimal or no comorbidities)
• Induction therapy
• The combination of cytarabine with an anthracycline or
anthracenedione is recommended.
• Cytarabine 100-200 mg/m2 continuous IV infusion for 7days plus
• Daunorubicin 60-90 mg/m2/day for 3days
• Liposomal daunorubicin-cytarabine (also known as CPX-351)
• Follow-up bone marrow to assess remission is typically done 7-14d after
completion of induction chemotherapy.
19. • Newly diagnosed therapy-related acute myeloid leukemia (t-AML) or
for or AML with myelodysplasia-related changes (AML-MRC) is as
follows
• First cycle: Daunorubicin 44 mg/m²
• cytarabine 100 mg/m² liposome
• IV on days 1, 3 and 5
• Second cycle: Daunorubicin 44 mg/m²
• cytarabine 100 mg/m² liposome IV on
• days 1 and 3 if needed.
• only for patients who do achieve remission with first induction cycle
20. Patients who achieve CR undergo postremission consolidation therapy,
undergo
• intermediate dose cytarabine,
• allogeneic HCT,
• autologous HCT,
• or novel therapies, based on their predicted risk of relapse (i.e., risk-
stratified therapy).
21. • Post remission therapy (consolidation)
• All patients should be assessed for risk of relapse. Specific drug regimens are
• recommended based on a patient’s risk of relapse.
• Better-risk patients
• Cytogenetics [inv (16) or t(16;16), t(8;21)] and molecular abnormalities
(normal cytogenetics : with NPM 1 mutation or isolated CEBPA mutation in
the absence of FLT3-ITD):
• High-dose cytarabine 3 g/m2 IV over 3h every
12h on days 1, 3, and 5 for four cycles
• High-dose cytarabine 3 g/m2 IV over 3h every 12h on
• days 1, 3, and 5 for two cycles plus autologous stem cell transplantation.
22. • Hematopoietic stem cell transplantation in younger patients
• In patients younger than 60 years, national comprehensive cancer network (NCCN)
guidelines recommend network (NCCN) guidelines recommend matched sibling or
alternate donor HSCT as an option in the following situations
• After induction failure with standard- dose or high-dose cytarabine
• After induction failure with standard-dose or high-dose cytarabine
• In patients with significant residual disease without a hypocellular marrow, after
high-dose cytarabine induction therapy
• As post-remission therapy in patients with intermediate-risk or poor- risk cytogenetics
and/or molecular abnormalities or those with treatment-related disease.
23.
24. • Treatment recommendations for patients ≥60 years
• There is no standard therapy for this patient population; a clinical trial is
preferred
• The following low-intensity therapies are recommended for patients ≥60y:
• azacytidine 75 mg/m2 IV or SC for 7d every 4-5wk
• Or decitabine 20 mg/m2 IV daily for 5d every 4-5wk or
• low-dose cytarabine 20 mg SC BID for 10days every 4wk
26. • Acute Lymphoblastic Leukaemia is defined as Malignant disease of
marrow in which early lymphoid precursors proliferate and replace
the normal Hematopoietic cells.
• It is the most common Malignancy in children of 2-10 years of age,
with peak incidence at 4-5 years of age.
• Has Bimodal distribution with 2nd peak at 65 years of age.
27. • Acute onset with short duration of history.
• 85% are B cell (Pre B ALL- Good prognosis)
• 15% are T cell
28.
29. • Acute Lymphoblastic Leukaemia is defined as Malignant disease of
marrow in which early lymphoid precursors proliferate and replace
the normal Hematopoietic cells.
• It is the most common Malignancy in children of 2-10 years of age,
with peak incidence at 4-5 years of age.
• Has Bimodal distribution with 2nd peak at 65 years of age.
32. TREATMENT OF ALL
• Induction therapy -
If Philadelphia Chromosome present -
Steroid + Tyrosine Kinase Inhibitor
If other mutations -
VADD regimen if Age <40 ( Vincristine, Asparaginase, Doxorubicin,
Dexamethasone)
Hyper CVAD regimen if Age > 40 ( Hyperfractionated
Cyclophosphamide, Vincristine, Anthracycline/Doxorubicin,
Dexamethasone)
33. CNS Prophylaxsis -
• Intrathecal Methotrexate + Cytarabine
• With or without WBRT (Whole Brain Radiotherapy) - in those with
high risk features :
1. WBC count >50000 at the time of presentation
2. T Cell phenotype
3. Ph Chromosome positive
4. t(4;11)
34. • Remission is defined as <5% blasts in bone marrow.
• Post Remission treatment is based on whether the patient belongs to
Standard risk or High risk group.
• For standard Risk, Consolidation therapy for 7 months , which is
followed by Maintenance phase for 2-3 years.
• For High risk , Re Induction with High Dose Chemotherapy, followed
by Allogenic Stem Cell Transplantation.
