Acute leukemia
A clinical overview
Common hematogenous malignancies
• Leukemia
–Acute
• Lymphoid
• Myeloid
–Chronic
• Lymphoid
• Myeloid
• Lymphoma
• Hodgkin’s
• Non-Hodgkin’s
Acute leukemia
• Acute myeloid leukemia
• Acute lymphoid leukemia
Etiologies of leukemia
• Genetics
• Oncogenic viruses
• Radiation
• Exposure to carcinogenic chemicals
• Immunosuppressive conditions
Clinical features
• General
• Anemia
• Granulocytopenia
• Thrombocytopenia
• Bone marrow expansion
• Leukemic infiltrations
Development of myeloid cells
Maturation of lymphoid cells
Myeloblast vs. Lymphoblast
Part I
ACUTE MYELOID LEUKEMIA
PBS in AML
Auer rods
AML
Peroxidase stain
FAB Classification of AML
Subtype of AML Incidence
M0: Minimally differentiated leukemia 5%
M1: Myeloid leukemia without maturation 20%
M2: Myeloid leukemia with maturation 30%
M3: Promyelocytic leukemia 10%
M4: Myelomonocytic leukemia 20%
M4Eo Variant: Increase in abnormal marrow eosinophils
M5: Monocytic leukemia 10%
M6: Erythroleukemia (DiGuglielmo's disease) 4%
M7: Megakaryoblastic leukemia 1%
WHO Classification of AML
I. AML with recurrent genetic abnormalities
II. AML with multilineage dysplasia
III. AML and myelodysplastic syndromes, therapy-
related
IV. AML not otherwise categorized
V. Myeloid sarcoma
VI. Myeloid proliferations related to Down
syndrome
VII. Blastic plasmacytoid dendritic cell neoplasm
VIII.Acute leukemia of ambiguous lineage
Myeloid sarcoma
Poor prognostic factors for AML
History
• Age> 60 yrs
• Prolonged symptomatic interval (> 1 month)
• H/O antecedent hematological disorder
• Associated co-morbidity
• Secondary AML (drug or radiation induced)
Clinical features
• Hepatomegaly
• Jaundice
• Respiratory distress (pulmonary leukostasis)
Lab investigations
• TLC > 1,00,000/ µL
• Hyperfibrinogenemia
• Auer rods +, adverse karyotype (Ph’+/ -5q/ -7q), MDR +
Favorable prognostic factors for AML
Chromosomal (Pre-treatment)
t (8:21) in M2
t (15:17) in M3
Inv (16) in M4 Eo
Post-treatment response
Blasts < 1%
Rapid disappearance of blasts from peripheral
blood
Investigations
• Baseline • Special
– CBC – Bone marrow
– Ur/ Cr – Uric acid
– CXR in PA view – LFTs
– ECG in 12 leads – BT, PT, APTT
– Karyotyping & cytogenetic
study
– HLA typing of patient &
potential donor
Treatment
• Resuscitation
• Induction of remission
• Remission consolidation
• Treatment of relapse
Treatment
Criteria for complete remission (CR)
• Peripheral blood
–Absolute neutrophil count > 1500/µL
–Platelet count > 1 lakh/µL
–No blast cells
• Bone marrow
–Cellularity > 20% with tri-lineage maturation
–<5% blasts
–Auer rods absent
• Absence of extramedullary leukemia
AML-M3
• Acute promyelocytic leukemia
• Caused by t(15;17)
• Associated with PML-RAR fusion gene
• Two variants:
–Hypergranular (75%) – better prognosis
–Microgranular (25%) – poor prognosis
• Often presents with DIC or pancytopenia
• Treated with ATRA (all trans retinoic acid)
Complications during treatment
• Hematological
–Anemia, Neutropenia, Thrombocytopenia
• Metabolic
–Hyperuricemia, Electrolyte disturbance
• Infectious
–Neutropenic sepsis, Blood transfusion related
• Systemic
–Nausea & vomiting, Hepatotoxicity, Nephrotoxicity,
Volume overload
Part II
ACUTE LYMPHOID LEUKEMIA
Lymphoid malignancies
I. Precursor B cell neoplasms
II. Peripheral B cell neoplasms
III. Precursor T cell neoplasms
IV. Peripheral T & NK cell neoplasms
V. Hodgkin’s lymphoma
ALL – small cells with uniform nuclei
ALL – heterogeneous cells with indented or
irregular nuclei
ALL – Large cells with vacuolar cytoplasm
FAB classification
CYTOLOGIC L1 L2 L3
FEATURES
CELL SIZE Small cells Large Large
Predominant heterogeneous in homogenous
size
AMOUNT OF Scant Moderate Moderate
CYTOPLASM
NUCLEOLI Inconspicuous One or more One or more
Prominent Prominent nucleoli
nucleoli
NUCLEAR SHAPE Regular Irregular with Regular;
indentation Oval or round in
shape
CYTOPLASM Variable degree of Variable degree of Deeply basophilic
basophilia basophilia cytoplasm with
vacuolation
Immunological classification
Immunologic FAB Subtype Cytogenetic Immuno-
Subtype Abnormalities phenotype
t(9;22), HLA DR+
Pre-B ALL L1, L2 t(4;11), CD 19+
t(1;19) CD 10+
14q11, CD 2+,CD 7+
T cell ALL L1, L2 7q34 CD 4+/5+/6+
t(8;14), CD 19+
t(8;22), CD 20+
B cell ALL L3 t(2;8) CD 21+
CD 22+
CNS leukemia
• More common in ALL
• Patients have high chance of relapse
• CNS is involved by:
Hematogenous spread
Seeding of meninges
Direct extension from cranial bones
• Signs:
RICT, meningism
CN palsy (VII, III, IV, VI)
CNS leukemia
• Diagnosis:
Lumber puncture
• Treatment:
Intra-thecal chemotherapy with MTX
Radio-therapy
Poor prognostic factors
• Old age
• TLC > 50,000/cmm
• Male sex
• L3 variant
• t(9;22), t(4;11), t(9;22)
Investigations
• Baseline • Special
– CBC – Lumbar puncture
– Ur/ Cr – Bone marrow
– CXR in PA view – Uric acid
– ECG in 12 leads – LFTs
– BT, PT, APTT
– Karyotyping & cytogenetic
study
– HLA typing of patient &
potential donor
Treatment
• Resuscitation
• Induction of Remission (IR)
–CNS prophylaxis
• Remission Consolidation
• Remission Maintenance
Complications during treatment
Criteria for complete remission (CR)
• Peripheral blood
–Absolute neutrophil count > 500/µL
–Platelet count > 1 lakh/µL
–No blast cells
• Bone marrow
–Cellularity – normal
–Blasts < 5%
• Absent extramedullary leukemia
Recurrent ALL
• Bone marrow
• Testes
• Meninges
Indications of BMT
• Relapse within 18 months of Induction therapy
• Relapse after 2nd induction
• Ph’+ ALL
Things to remember
• Classification of Leukemia
• Clinical features of ALL and AML
• Diagnosis of ALL and AML
• Treatment of ALL and AML
• Acute promyelocytic leukemia
• Myeloid sarcoma
