Acute Leukamias Final Yr 2010

7/28/2019 Acute Leukamias Final Yr 2010

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Prof. Iftikhar Ali Shah


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Leukemia is a cancer of the bloodor bone marrow characterized byan abnormal proliferation of

blood cells, usually white bloodcells (leukocytes).


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Cancer of the white blood cells Acute or Chronic

Affects ability to produce normal blood cells

Bone marrow makes abnormally large numberof immature white blood cells called blasts


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Acute Lymphocytic Leukemia (ALL)

Acute Mylogenous Leukemia (AML)

Chronic Lymphocytic Leukemia (CLL)

Chronic Mylogenous Leukemia (CML)


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ALL

11%

CLL

26%

AML

31%

CML

15%

others

17%

Total Reported Cases = 31,500Sources from Leukemia,Lyphoma, Myeloma Facts 2001

CLL=ChronicLymphocytic

ALL=AcuteLymphocytic

CML=Chronic

MylogenousAML=AcuteMylogenous


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Craigie and Bennett described a case ofsuppuration of the blood in 1845.Subsequently referred to the disease asleukocythemia

Rudolph Virchow, also in 1845, described asimilar case, but did not think this simplypus in the blood and related it tosimultaneous splenic enlargement.

Subsequently referred to the disease asWeisses Blutthen suggested the termleukemia

INCTR2004


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thick as gruel

the consistency and color of the yeast of red wine


10/125N Engl J Med 2003; 349:767, Aug 21, 2003. Images in Clinical Medicine

WBC 249

Hb 2.8

leukemia

Greek words "leukos" meaning

"white" and "haima" meaning"blood,


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It is more commonly known as AML It is a cancer of the blood that affects the

cells producing myeloid blood cells

First recognized in 1830 in Germany

Physician referred to it as weisses blut

The term leukemia stems from the Greekwords leukos and haima


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~15,000 new cases of acuteleukemia per year in the US

11,920 AML

3,700 ALL

~70% of new cases of acute

leukemia are AML Most cases occur in adults

Median age is 60

Incidence rises in individuals 60 yearsand older

3-4/100,00010/100,000

Children AML comprises ~15% of acute

leukemias

AML is more common in

The first year of life

Certain high risk groups (Downssyndrome)


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The termMyelogenousdenotes what typeof cell is beingaffected: Monocytesand Neutrophils

Acute refers to

rapid progressionforming immaturecells

Results fromacquired geneticdamage to the DNAof the bone marrow

Immature cellsproduced areknown as blast

cells


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Acute ChronicMyeloi

dorigin

Lymphoidorigin

Acute MyeloidLeukemia (AML)

AcuteLymphoblasticLeukemia (ALL)

Chronic Myeloid Leukemia(CML)

Chronic LymphocyticLeukemia (CLL)


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Leukemia

Myeloid Lymphoid

Acute

(AML- 8 types)

Chronic

(CML)

Acute

(ALL- 3 types)

Chronic

(CLL)


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This microscope imageshows AML cells (acutemyeloblastic leukemia;also referred to as ANLL,acute nonlymphocyticleukemia). Certaininternal cell structures aretypical of AML. Theseinclude prominentnucleoli (red arrows) andcytoplasmic granules

(grainy structures insidethe cell which indicatesome degree of cellmaturation--black arrow).


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Normal human blood

White Cell Red Cell

Platelet

Blood with leukemia

BlastsRed Cell

Platelet

White Cell

Sources fromArginine.umdnj.edu

Sources from beyond2000.com


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Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis

Stage 4- Worsening

Stage 5a- Anemia

Stage 5b- Infection

Legend

White Cell

Red Cell

Platelet

Blast

Germ Sources from Leukemia, by D. Newton and D.Siegel


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Features Myeloblasts Lymphoblasts

Cytoplasm Mod/abundant Scant/Mod

Cyt. Granules Common Uncommon

Nucleus

(chromatin)

fine Coarse

Nucleoli Prominent Variable

Auer rods Present Absent


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Hematopoieticstem cell

Neutrophils

Eosinophils

Basophils

Monocytes

Platelets

Red cells

Myeloidprogenitor

Lymphoidprogenitor

B-lymphocytes

T-lymphocytes

Plasmacells

nave

ALL

AML


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AML

French-American-B ri t ish (FAB) Class i f icat ion

M0: Minimally differentiated leukemia

M1: Myeloblastic leukemia without maturation

M2: Myeloblastic leukemia with maturation

M3: Hypergranular promyelocytic leukemiaM4Eo: Variant: Increase in abnormal marrow

eosinophils

M4: Myelomonocytic leukemia

M5: Monocytic leukemiaM6: Erythroleukemia (DiGuglielmo's disease)

M7: Megakaryoblastic leukemia

Ref-Harrisons Principle of Internal Medicine


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AML with certain genetic abnormalities t(8;21), t(16), inv(16), chromosome 11 changes t(15;17) as usually seen with AML M3

AML with multilineage dysplasia (more than one abnormal myeloid cell typeis involved)

AML related to previous chemotherapy or radiation AML not otherwise specified

undifferentiated AML (M0) AML with minimal maturation (M1) AML with maturation (M2) acute myelomonocytic leukemia (M4) acute monocytic leukemia (M5) acute erythroid leukemia (M6) acute megakaryoblastic leukemia (M7) acute basophilic leukemia

acute panmyelosis with fibrosis myeloid sarcoma (also known as granulocytic sarcoma or chloroma)

Undifferentiated or biphenotypic acute leukemias (leukemias that have bothlymphocytic and myeloid features. Sometimes called ALL with myeloidmarkers, AML with lymphoid markers, or mixed lineage leukemias.)


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Cytogenetic changes can determine prognosis(chance of recovery), influence the choice oftreatment, and help predict the results oftreatment

Favorable: presence of changes associated with agood outcome after treatment

Intermediate: presence of changes associatedwith a less favorable prognosis

Unfavorable: presence of changes associated witha poor prognosis


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idiopathic (most) underlying hematologic disorders

chemicals, drugs

ionizing radiation viruses (HTLV I)

hereditary/genetic conditions


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Unknown / De-novo !! In majorityPredisposing factors: Ionizing radiation exposure Previous chemotherapy : alkylating agents Occupational chemical exposure : benzene Genetic factors: Downs Syndrome, Blooms,

Fanconis Anemia Viral infection ( HTLV-1) Immunological : hypogammaglobulinemia Acquired hematological condition -Secondary


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Age

High doses of radiation

Previous chemotherapy treatment Certain genetic disorders

Smoking


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Down syndrome

Ataxia telangiectasia

Li-Fraumeni syndrome

Klinefelters syndrome

Fanconis anemia

Wiskott-Aldrich syndrome

Blooms syndrome


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symptoms due to: marrow failure

tissue infiltration

leukostasis

constitutional symptoms other (DIC)

usually short duration of symptoms


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neutropenia: infections, sepsis anemia: fatigue, pallor

thrombocytopenia: bleeding


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enlargement of liver, spleen, lymph nodes gum hypertrophy

bone pain

other organs: CNS, skin, testis, any organ


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Fatigue

Weakness

Easy bruising or bleeding

Weight loss Fever

Bone or abdominal pain

Difficulty breathing; dyspnea (shortness of breath)

Frequent infections Swollen lymph nodes

Swollen or bleeding gums


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A

B

C

NEJM 1998


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Mani, A, Lee, DA. Leukemic Gingival Infiltration. N Engl J Med 2008; 358(3): 274. Copyright 2008 Massachusetts MedicalSociety


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Extramedullary disease (ie, myeloidsarcoma) Can also have involvement of lymph nodes,

intestine, mediastinum, ovaries, uterus


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Skin Infiltration with AML (Leukemia Cutis)


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accumulation of blasts in microcirculationwith impaired perfusion

lungs: hypoxemia, pulmonary infiltrates

CNS: stroke

only seen with WBC >> 50 x 109/L


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Leukostasis predominantly in those withWBC counts > 100,000 (10% of patients);can also be seen in patients with WBC >50,000 Most common in those with M4 or M5 leukemia

Function of the blast cells being less deformablethan mature myeloid cells. As a result,intravascular plugs develop.

High metabolic activity of blast cells and localproduction of various cytokines contribute tounderlying hypoxia


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Thornton, KA, Levis, M. FLT3 Mutation and Acute Myelogenous Leukemia with Leukostasis. N Engl J Med 2007; 357:1639.Copyright 2007 Massachusetts Medical Society


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Common symptoms Pulmonary: dyspnea, chest pain

CNS: headaches, altered mentation, CN palsies,ocular symptoms

Priapism Myocardial Infarction


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Treatment Chemotherapy with induction agents (e.g

cytarabine, anthracycline) or with high dosehydroxyurea

Consider low dose cranial irradiation to preventcell proliferation in the CNS (can see intracranialhemorrhage in patients with leukostasis)

Avoid PRBC transfusion if possible as additionalblood elements contribute to the hyperviscosity

In patients that are unable to undergo immediatechemotx (e.g renal insufficiency, metabolicderangements, etc), leukapheresis is a 2nd option


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Leukapheresis Limited affect on established vascular plugs Limited benefit in those with underlying

pulmonary symptoms following chemotx.Symptoms in this case related to leukocyte lysisand subsequent inflammatory response

Should not be used as a single modality agent inpatients with leukostasis (unless chemotx isdelayed)

May consider as adjunct to chemotx in patientswith WBC >100,000 and symptoms suggestive ofleukostasis


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WBC usually elevated, but can be normal orlow

blasts in peripheral blood

normocytic anemia

thrombocytopenia

neutropenia

DIC


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necessary for diagnosis useful for determining type

useful for prognosis

Acute leukemias are defined by the presenceof > 20% blasts in bone marrow (% ofnucleated marrow cells)


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Note the myeloblasts and the auer rod:


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AML


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AML


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M2 myeloblastic with maturation The bone marrow shows 30-89% blasts and > 10%

promyelocytes;

This is characterized by an 8,21 chromosomal translocation

This occurs in older adults

M3 hypergranular promyelocytic This form of AML has a bone marrow with >30% blasts

Is more virulent than other forms

Occurs with a medium age of 39

The WBC count is decreased

Treatment causes a release of the granules and may send the

patient into disseminated intravascular coagulation andsubsequent bleeding

It is characterized by a 15,17 chromosomal translocation


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Note myeloblasts and hypogranulated PMNs:


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Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,

fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.


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Note hypergranular promyelocytes:


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Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.


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Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.


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Auer Rods in Leukemia cells


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M3m hypogranular promyelocytic The bone marrow has > 30% blasts

The WBC count is increased.

Like the M3 type, treatment causes a release of the granulesand may send the patient into disseminated intravascular

coagulation and subsequent bleeding and It is characterized by a 15,17 translocation

M4 acute myelomonoblastic leukemia

Both myeloblasts and monoblasts are seen in the bonemarrow and peripheral blood

Infiltration of extramedullary sites is more common than withthe pure granulocytic variants


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Note hypogranular promyelocytes:


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From Brunning, RD, McKenna, RW. Tumors of the bone marrow. Atlas of tumor pathology (electronic fascicle), Third series,fascicle 9, 1994, Washington, DC. Armed Forces Institute of Pathology.


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M5 acute monoblastic leukemia >80% of the nonerythroid cells in the bone marrow are monocytic

There is extensive infiltration of the gums, CNS, lymph nodes andextramedullary sites

This form is further divided into

M5A - Poorly differentiated (>80% monoblasts)

M5B - Well differentiated (


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Note monoblasts:


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Note monoblasts, promonocytes, andmonocytes:


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Note M1 type monoblasts


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M7 - Acute megkaryoblastic leukemia This is a rare disorder characterized by extensive

proliferation of megakaryoblasts, atypical megakaryocytesand thrombocytopenia


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MyeloblastsMyeloperoxidase (MPS) positive
http://www.hmds.org.uk/insets/821d.htm


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MPO (right) & Sudan black (left)showing intense localisedpositivity in blasts
http://www.hmds.org.uk/insets/821d.htm


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Choice of Rx is influenced by: type (AML vs ALL)

age

curative vs palliative intent


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Favorable younger age (80% AML M3

Unfavorable

older age (>60) Poor performance status WBC >100,000 Elevated LDH prior MDS or hematogic malignancy CD34 positive phenotype, MRD1 postive phenotype del (5), del (7)

trisomy 8 t(6;9), t(9;22) t(9;11) seen in AML M5 FLT3 gene mutation (seen in 30% of patients)


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Treatment depends on subtype, morphology,cytogenetics, and the patients overall health

Chemotherapy (options include a

combination of drugs) Radiation therapy

Bone marrow transplantation/stem cell

transplantation

More than one treatment may be used


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Drugs used to killcancer cells Primary treatment for

AML Systemic

chemotherapy is givendirectly into thebloodstream, or bymouth, targetingcancer cellsthroughout the body

Chemotherapy mayalso be injected intothe cerebrospinal fluid

Divided into threephases: remissioninduction, post-remissionconsolidation, andmaintenance (not

commonly used inAML)

Side effects mayinclude hair loss,mouth sores, fatigue,

infection, bleeding,nausea, vomiting, andinfertility


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Initial period of treatmentafter diagnosis

Intensive therapy kills bothleukemia cells and healthy

cells

Goal is complete remission(normal blood counts, noevidence of leukemia in

bone marrow, and no AMLsymptoms)

Combination therapy ofcytarabine (Cytosar-U) anddaunorubicin (Daunomycin,Cerubidine) or idarubicin(Idamycin) is common

May require hospitalizationfor three to five weeks

May require two courses of

induction chemotherapy forcomplete remission


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Used to kill remaining AML cells after successfulinduction

Two to four courses of high-dose cytarabine isused for younger adults in remission

Many different regimens are used for olderpatients

Stem cell transplantation may be recommendedinstead


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High-dose chemotherapy used to kill cancer cells

New stem cells are introduced from the patient(autologous) or a donor (allogeneic) to form newblood cells

May be used for patients at high risk for recurrence

Graft-versus-host disease: a serious complication inwhich the donors immune cells attack the patientshealthy cells


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The use of high-energy x-rays or otherparticles to destroy cancer cells

External beam: outside the body

Used most often for AML that has spread tothe brain or to shrink localized masses calledchloromas

Side effects may include fatigue, mild skinreactions, nausea and vomiting, and diarrhea


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Inhibition of the products of genetic mutationsfound in AML cells

Inhibition of proteins that cause chemotherapyresistance

Use of antibody therapy against AML cells

Use of new or existing drugs given in differentdoses and schedules

Techniques to make stem cell transplantation safer,easier, and more effective

Evaluation of drugs called hypomethylating therapy


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combination chemotherapy first goal is complete remission

further Rx to prevent relapse

supportive medical care

transfusions, antibiotics, nutrition psychosocial support

patient and family


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Phases of ALL treatment induction intensification CNS prophylaxis maintenance

Phases of AML treatment induction consolidation (post-remission therapy)

post-remission therapy


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permits rescue from otherwise excessivelytoxic treatment

additional advantage of graft-vs-leukemiaeffect in allogeneic transplants

trade-off for allogeneic transplantation:greater anti-leukemic effect but more toxic


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Acute Lymphoblastic Leukemia is the most common malignancy ofchildhood, accounting for 1/3 of all childhood cancers.

Approximately 2400 cases diagnosed in the United States each year.

Incidence 4 per 100,000 children under age 15.

The annual incidence in India would be approximately 10.000 childrenper year.

The peak incidence is approximately 4 years of age.

More common in boys and in white children.

The exact cause is known and it could be combination of genetic andenvironmental factors.


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Most common childhood acute leukemia,~80%

Incidence in adults ~20%

Bimodal distribution of occurrence: Peak at age 2-5 Second increased incidence after age 50


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Acquired Genetic Change in Chromosome Change in number, ie ploidy

Change in structure Translocations (most common)

Inversions Deletions

Point mutations

Amplifications

Changes in normal means of cell differentiation, proliferation,

and survival


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Unknown ? Genetic Predisposition

Increased incidence amongst monozygotic and dizygotic twins

Down Syndrome Disorder with chromosomal fragility:

Fanconis anemia

Bloom Syndrome Ataxia-Telangiectasia

? Infections HTLV1 in T cell leukemia/lymphoma EBV in mature B cell ALL HIV in lymphoproliferative DO


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ImmunologicSubtype

% of cases FAB Subtype CytogeneticAbnormalities

Pre-B ALL 75 L1, L2 t(9;22), t(4;11), t(1;19)

T cell ALL 20 L1, L2 14q11 or 7q34

B cell ALL 5 L3 t(8;14), t(8;22), t(2;8)

From: Harrisons Principles of Internal Medicine,16th ed. 2005. Chapter 97, Malignancies of


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Nonspecific Symptoms Fatigue/decreased energy Fever Easy bruising Bleeding Dyspnea Dizziness Infection

Joint, extremity pains CNS involvement


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Physical Exam Pallor

Ecchymoses

Petechiae

LAD Hepatosplenomegaly

Lab Abnormalities anemia

wbc vary 0.1 (20-40%) - >100 k

(10-16%)

Platelets usually

LD, uric acid

CXR: eval for thymic mass

CSF to eval for

involvement


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ITP Aplastic Anemia

Infectious mononucleosis

Rheumatoid Arthritis

Rheumatic Fever

Collagen Vascular Disease


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Morphologic

French American British Classification

L1: small uniform blasts (pediatric ALL)

L2: larger, more variable sized blasts (adult ALL) L3: uniform cells with basophilic and sometimes

vacuolated cytoplasm (mature B cell ALL)


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Acute lymphoblasticleukemia (ALL)*

L-1 85%

L-2 14%

L-3 (Burkitt's)1% childhood


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Acute lymphoblastic leukemia They may be classified on the basis of thecytological features of the lymphoblasts into; L1 - This is the most common form found in children

and it has the best prognosis. The cell size is small withfine or clumped homogenous nuclear chromatin and

absent or indistinct nucleoli. The nuclear shape isregular, occasionally clefting or indented. The cytoplasmis scant, with slight to moderate basophilia and variablevacuoles.

L2 This is the most frequent ALL found in adults. Thecell size is large and heterogenous with variable nuclear

chromatin and prominent nucleoli. The nucleus isirregular, clefting and indented. The cytoplasm isvariable and often moderate to abundant, the basophiliais variable and may be deep, and vacuoles are variable.


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L3 This is the rarest form of ALL. The cell size islarge, with fine, homogenous nuclear chromatincontaining prominent nucleoli. The The nucleus isregular oval to round. The cytoplasm is moderatelyabundant and is deeply basophilic and vacuolated.


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Incidence ALL is primarily a disease of youngchildren (2-5 years), but it can also occur in adults

Clinical findings pancytopenia with resultingfatigue, pallor, fever, weight loss, irritability,anorexia, infection, bleeding, and bone pain.

L1 occurs in children, L2 in adults, and L3 is calledBurkitts leukemia


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Prognosis age, WBC count, and cell type are themost important prognostic indicators Patients younger then 1 and greater than 13 have a poor

prognosis

If the WBC count is < 10 x 109/L at presentation, the

prognosis is good; If the WBC count is > 20 x 109/L atpresentation the prognosis is poor

T cell ALL (more common in males) has a poorerprognosis than any of the B cell ALLs which have a curerate of 70%


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Acute Lymphoblastic Leukemia - L1

Morphology: L1 blasts are small and homogeneous.The nuclei are round and regular with little cleftingand inconspicuous nucleoli. Cytoplasm is scanty

and usually without vacuoles. Staining: MPO is always negative. When is a biopsy necessary ?

possible severe aplastic anemia to investigate bone marrow involvement of

lymphoma, solid tumor dry tap -> touch prep from biopsy core possible myelofibrosis (e.g. leukemia in Down)


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ALL(Lymphoblast) Blast size :small Cytoplasm: Scant Chromatin: Dense Nucleoli :Indistinct Auer-rods: Never

present

AML (Myeloblast) Large

Moderate

Fine, Lacy

Prominent Present in 50%


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2. Bone marrowaspiration andtrephine biopsy

confirm acuteleukaemia(blast > 30%)

usuallyhypercellular


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1 Remission Induction 2 Intensification (Consolidation) Therapy

3 Maintenance Therapy

4 CNS Prophylaxis

5 Allogeneic Stem Cell Transplant


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Supportive therapy/Treatment of complications

Definitive therapy

CHEMOTHERAPY

STEM CELL TRANSPLANTATION


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Supportive therapy/Treatment of complications

Definitive therapy

CHEMOTHERAPY

STEM CELL TRANSPLANTATION


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Treatment of tumor lysis (hydration, bicarbonate,allopurinol/recombinant urate oxidase)

Appropriate Treatment of febrile neutropenia

Transfusion of blood products

Nutritional support

Five-year DFS was 83% for well-nourished children

(WNC) and 26% for under-nourished children (UNC)(p< 0.001


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ALL

Infants


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ALL

B precursor T-lineage

Treatmentstratification-overview

3-drug or 4-drug induction (NCI criteria ) T cell: 4-drug

stand. high very high risk T cell protocol


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dexamethasone

vincristine

L-asparaginase (PEG)

intrathecal chemotherapy (Ara-C day 1, MTX day 8

and, 29)

BM aspirate: day 1, 8 (if not M1 also d15) and 29 (MRD)

Lumbar puncture: day 1, 8, 29

Portacath


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dexamethasone (14 days, 10mg/m2) orprednisone (60mg/m2/d)

vincristine L-asparaginase (PEG) daunorubicin intrathecal chemotherapy (Ara-C day 1, MTX day 8

and, 29)

BM aspirate: day 1, 8 (if not M1 also d15) and 29 (MRD)Lumbar puncture: day 1, 8, 29

Portacath


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One of the key drugs in childhood ALL and acts bydepletion of asparagine which is essential for survival ofmalignant lymphoblasts.

3 preparations half life Asparagine

E Coli asparaginase 1.280.35d 14-23dErwinia asparaginase 0.650.13d 7-

15d

PEG asparaginase 5.733.24d 26-34d

Side effects (anaphylaxis, bleeding, thrombosis,pancreatitis and diabetes)


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CNS Status

Response to treatment

Blast count in PB/BM

MRD

Cytogenetics


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CNS Status

CSF cell count and cytospin

< 5 WBC, no blasts CNS 1

< 5 WBC, blasts CNS-2> 5 WBC, blasts CNS-3


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Definitions M1 < 5% blastsM2 5-25% blastsM3 >25% blasts

Bone marrow on day 7rapid early response (RER)slow early response (SER)

Peripheral blast count after 1 week of prednisone(1x10 9/lt)prednisone good response 82% 6-year EFSprednisone poor response 34%

.

MRD


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COG

RER

M1 on day 8 AND

negative MRD on d29 M2, M3 on day 8 but M1 on day 15 AND

negative MRD on d29

SER

M2 or M3 on d15 ORpositive MRD on d29


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Low risk Hyperdiploidy Trisomy 4,10,17 T(12:21)(TEL:AML)

Standard risk No triple trisomies or TEL:AML)

High risk Chr 11 abn (MLL gene rearrangement)

Very high risk t(9:22)(bcr:abl), hypodiploidy


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The testis and CNS are the sanctuary sites.

The incidence of CNS Relapse was 10-20% in 1980s.

Cranial RT with 18-24c Gy reduced the risk to 1%.

Concern about the long term side effect of cranial RTwith secondary brain tumours always remains.

High dose methotrexate with IT Methotrexate was foundto be equally effective in preventing CNS Relapse.


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Main drugs (oral methotrexate and 6 mercaptopurine) Duration of therapy( from Interim Maintenance)

boys 3 years

girls 2 years

Target ANC (between 750-1500) Administration of 6 Mercaptopurine in empty stomach in

evening.

Addition of Vincristine and dexamethasone pulses everymonth

Intrathecal methotrexate every 3 month Compliance is the key to success


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Very high risk ALL (defined by CCG, AND POG)

presence of the t(9;22),M3 marrow on day 29 (M3=>25% blasts )M2 or M3 marrow on day 43(M2=5-25% blasts)hypodiploidy (


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equal distribution of lymphoid and myeloid leukemia

4% of pediatric ALL (45% diagnosed during first 6 m)

identical clone specific mutations are present in monozygotic twins

Typical infant ALL-high white cell count, usually CD10 negative preB ALL and MLL gene rearrangement involving 11q chromosome in2/3 rd patients

Outcome -35-45%

Presentation earlier than 6 month of age ,CD10 negativity, presenceof MLL gene are associated with bad prognosis.


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Constitute 10-20% of childhood ALL

Associated with adverse prognostic features High white cell count T cell immunophenotype Low leukemic cell DNA index Lower frequency of favourable cytogenetic features like TEL:AML

and hyperdiploidy Higher frequency of unfavourable cytogenetic feature like

philadelphia chromosome

Treatment with pediatric protocols have been proved to have better

outcome compared to adult protocols (65-75% vs 35-45%) (DiAngelio ASH Education 2005)


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Constitute 25% of childhood cancers

Prognostic factors of ALL relapse

time point after diagnosis of primary ALL

site

immunophenotype

treatment intensity(interval between early treatment elements)


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Acute Leukamias Final Yr 2010

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