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CHRONIC
LEUKEMIA
Leukemia
Legend
Stage 5a- Anemia
White Cell
Red Cell
Platelet Stage 4- Worsening
Blast
Stage 5b- Infection
Germ
ALL
nave
B-lymphocytes
Plasma
Lymphoid cells
progenitor T-lymphocytes
AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Types of Leukemia
Acute Lymphoblastic Leukemia (ALL)
Weight loss
Fever
Hyperkalemia
Hyperuricemia
Acute Leukemia:
Clinical Manifestations
Marrow
replacement, organ infiltration
& metabolic effects
Marrow replacement
Neutropenia: infection
Anemia: pallor, fatigue, dyspnea
Thrombocytopenia: abnormal
bruising and bleeding
Acute Leukemia:
Clinical Manifestations
Organ infiltration
Bone pain
Hepatosplenomegaly
Lymphadenopathy
Gingival hypertrophy
Leukemic meningitis
AML:
FAB classification
French American British classification
Historically,
distinguishing AML M0 from
ALL was a major clinical problem
AML
FAB classification
M0,M1, M2: Myeloblasts with no, little or
some granulocytic maturation
M3: Promyelocytic leukemia
M4: Myelomonocytic or eosinophilic
M5: Monocytic
M6: Erythroleukemia
M7: Megakaryoblastic
A. Morphology of cells.
B. Degree of maturation of cells.
C. Immunologically immature blasts in
ALL.
D. CLL affects mainly elderly.
SYMPTOMS of CLL
Night sweat
Infections esp pneumonia
TREATMENT OF CLL
Observation
Chemotherapy. Oral chlorambucil
Fludarabine,
Immunotherapy Anti-CD 20 (rituximab),
Anti-CD 52 (Alemtuzumab)
Indications for starting chemotherapy
a. Progressive Symptoms
b. Progressive Anemia or Thrombocytopenia
c. Bulky LN, large spleen
d. Recurrent Infections
CHRONIC MYELOID
LEUKEMIA
CML is a clonal stem cell disorder
characterised by increased proliferation
of myeloid elements at all stages of
differentiation.
Reciprocal translocation of
chromosomal material between
chromosome 22 and chromosome 9.
t(9;22)
Treatment
ACUTE LYMPHOBLASTIC LEUKEMIA ( ALL)
DOSE ROUTE REGIMEN
Induction ( 4 weeks)
Vincristin 1.5 mg/m2 I.V Weekly for 4 weeks
Prednisolone 40mg/m2 Oral Daily for 4 weeks
L- Asparaginase 6000u/m2 I.M 3xWeekly for 3
Daunorubicin 45mg/m2 I.V weeks
Daily for 2 days
Intensification(1 week)
Vincristin 1.5mg/m2 I.V 1 dose
Daunorubicin 45mg/m2 I.V Daily for 2 days
Prednisolone 40mg/m2 Oral Daily for 5 days
Etoposide 100mg/m2 I.V Daily for 5 days
Cytarabine 100mg/m2 I.V 2x daily for 5 days
Thioguanine 80mg/m2 Oral Daily for 5 days
CNS Prophylaxis( 3 weeks)
Cranial irradiation 24 Gy
Methotrexate I.T weekly for 3 weeks
Maintenance Therapy ( 2
years) 20mg/m2 Oral Weekly
Methotrexate 75mg/m2 Oral Daily
6-Mercaptopurine 40mg/m2 Oral 5days/ Month
Prednisolone 1.5mg/m2 I.V Monthly
vincristine
(Treatment of acute
leukemias)Induction
Obtained by using high doses of chemotherapy
1 Severe bone marrow hypoplasia
2 Allowing regrowth of normal residual stem cells to
regrow faster than leukemic cells.
Remission
Normal neutrophil count
Normal platelet count
Normal hemoglobin level
Remission defined as < 5% blast in the bone marrow
(Treatment of acute leukemia)
Consolidation
Different or same drugs to those used during
induction
Induction Induction
Consolidation Consolidation
Maintenance No maintenance
Daunorubicin Cladribine
Doxorubicin Cytarabine
Idarubicin Fludarabine
Hydroxyurea
Mitoxantrone
Methotrexate
6-Mercaptopurine
6-Thioguanine
DRUGS USED TO TREAT ACUTE
MYELOBLASTIC LEUKEMIA (
AML)
TOPOISOMERASE CELL MATURING AGENT
INHIBITORS
ALL-TRANS RETIONIC ACID
ETOPOSIDE (ATRA)
TOPOTECAN ARSENIC TRIOXIDE
CYCLOPHOSPHAMIDE AZACITIDINE
CARBOPLATIN DECITABINE
TEMOZOLOMIDE
Treatment of Chronic
Lymphoblastic Leukemia (CLL)
Alkylatingagents :
Chlorambucil intermittently (10 mg/m2 x 7
days, monthly ) or continously ( 5 -10 mg /
day )
Combinations :
COP : Cyclophosphamide, Oncovin,
Prednisolone( 5 day monthly course )
Chlorambucil + Epirubicin
CHOP : COP + Doxorubicin
Treatment of Chronic
Lymphoblastic Leukemia (CLL)
Corticosteroids :
Prednisolone : 30 mg / m2 for 3 weeks + 1 week tailing
off for initial treatment of pts with Stage C disease.
High dose Methylprednisolone IV at 1 g/m2 ( 5-day
monthly course )
Nucleoside analogues :
Fludarabine ( 25 mg / m2 IV daily as 30 min infusion for
5 days every 28 days )
Fludarabine + Cyclophosphamide
Pentostatin ( 2 mg/m2/day IV for 5 days every 28
days)
Cladribine ( IV infusion over 2 hrs dose of 0.12
mg/kg/day for 5 consecutive days )
Nucleoside analogues
Studies have shown FLUDARABINE
superior to Chlorambucil in CLL with
higher clinical response rates, superior
time to treatment failure, better tolerance
in pts > 65 yrs.
FLUDARABINE Currently 1st line of
treatment in CLL
Monoclonal Antibodies
Alemtuzumab ( monoclonal antibody directed at
CD 52 ) :
1st line agent
For salvage in pts with fludarabine refractory
disease
Effective in CLL with p53 mutations
Very effective in clearing Bone Marrow disease
Limited activity in clearing bulky
lymphadenopathy
Has role in consolidation therapy for elimination of
minimal residual disease.
Monoclonal Antibodies
Anti-viral prophylaxis and prophylactic antibiotics for
Pneumocystis carnii are recommended for pts
receiving Alemtuzumab and for 2 4 months after
treatment
Rituximab (monoclonal antibody specific for CD 20)
used extensively in combination with chemotherapy.
Fludarabine combined with Rituximab shown higher
clinical remission rates than fludarabine alone .
FCR ( Fludarabine, Cyclophosphamide, Rituximab )
shown clinical response rates of 76% in trials.
CFAR ( Cyclophosphamide, Fludarabine,
Alemtuzumab, Rituximab ) still under trials
Monoclonal Antibodies
LENALIDOMIDE : An immunomodulatory
drug currently approved for use in
Multiple Myeloma and MDS with deletion
of Chr 5q .
Studies have shown response rates of 47
38 % with complete response rates of 9 %
and elimination MRD have been
reported.
Bone Marrow Transplantation
Allogenicbone marrow transplantation is
the only known curative therapy.