acuteleukemiacomplt-161017163342 (1).pptx

- Is a group of malignant (neoplastic) disorders , characterized
by the clonal expansion and accumulation of one or more blood
cell line(s) , with eventual involvement of all hematopoietic
organs and other organs.
Leukemia

Leukemia
Tow or more Mutations within the genome of HSC or multipotential
progenitors/precursors
Activation of specific proto-oncogene
De-activation of tumor suppressor genes
Clone of cells with characteristics of a malignant cell
• Prolonged life (immortal) resistant to apoptosis
• Growth factor independent growth
• Insensitivity to growth-inhibitory signals
• Ability to invade and metastasize
• Blockage of intracellular differentiation

Leukemia
• CBC and blood film examination :
- Normocytic normochromic anemia (mild to severe)
- Platelets count: reduced to normal
- WBC’s count: decreased mature leukocytes
- The appearance of abnormally circulating blood cells (malignant
cells)
• BM aspirate and/or biopsy
- B.M. hyperactivation and hyperplasia
- Blasts : represents greater than 20 - 30% depends on the type of
Classification and type of Leukemia .

Hematopoietic
stem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Plasma
cells
T-lymphocytes
naïve
B-lymphocytes
ALL
Lymphoid
progenitor
AML
Myeloid
progenitor

Leukemia
• Cytochemistry:
Cytochemical Reaction
Cellular Element
Stained
Blasts Identified
Myeloperoxidase (MPO)
Neutrophil primary
granules
Myeloblasts strong positive;
monoblasts faint positive
Lymphoblast Negative
Sudan Black B (SBB) Phospholipids
Myeloblasts strong positive;
monoblasts faint positive
Lymphoblast Negative
Specific esterase Cellular enzyme Promyelocyte stage positive
Nonspecific esterase
(NSE)
Cellular enzyme
Monoblasts strong positive
Others Negative
Periodic acid-Schiff
Glycogen and
related substances
lymphoblast's and pronormoblasts
Negative to Positive .
Myeloblasts usually negative.
Metamyelocyte & PMN Strong +ve

Acute Myeloid Leukemia
-Malignant neoplastic proliferation and accumulation
of immature and nonfunctional myeloid line of blood
cells in the bone marrow .
-Also known as acute myelogenous leukemia or acute
nonlymphocytic leukemia (ANLL)
- Most common Acute Leukemia affecting adults.
- As an Acute Leukemia, AML progresses rapidly and is typically
fatal within weeks or months if left untreated .

Myeloid maturation
myeloblast promyelocyte myelocyte metamyelocyte band neutrophil
MATURATION
Adapted and modified from U Va website

Etiology
• Heredity
– Down syndrome
– Fanconi anemia
– Bloom syndrome
– ataxia-telangiectasia
– Congenital neutropenia (Kostmann syndrome)
• Radiation
– High-dose radiation (atomic bombs survivors)

• chemical and occupational
exposures
– Benzene
– petroleum products
– Paint
– embalming fluids
– ethylene oxide
– Herbicides
– smoking
•
• Drugs
– Alkylating agent
– Topoisomerase II inhibitor
– Chloramphenicol
– Phenylbutazone
– Chloroquine
– methoxypsoralen

Pathophysiology
- In AML, a single myeloblast genetic changes which "freeze"
the cell in its immature state and prevent differentiation.
- When such a "differentiation arrest" is combined with other
mutations which disrupt genes controlling proliferation, the
result is an uncontrolled growth of an immature clone of
cells, leading to the clinical entity of AML .
-

Pathophysiology
- Thegrowth of leukemic clone cells, which tends to displace
or interfere with the development of normal blood cells in
the bone marrow .
- This leads to neutropenia, anemia, and thrombocytopenia.
The symptoms of AML are often due to the low numbers of
these normal blood elements.

Clinical Presentation
• Nonspecific symptoms
• Fatigue
• Anorexia
• Weight loss
• Fever
• Bleeding, easy bruising
• Bone pain, lymphadenopathy, nonspecific
cough, headache, or diaphoresis

Physical Findings
• Fever
• Splenomegaly
• Hepatomegaly
• Lymphadenopathy
• Sternal tenderness
• Evidence of infection and hemorrhage

Laboratory findings:
1 Peripheral Blood:
- The leukocyte count ranges from < 1X109 to >100X109 .
- Presence of blast on the blood smear.
-Neoplastic blast have few granules in the RNA rich
cytoplasm.

Laboratory findings:
- Erythrocyte decreased, Hb less than 10g/dl
-Slightly Macrocytic because of the inability to compete
the neoplastic cell for folate and vitB12 or early release of
Retic cells.
2- Bone marrow:
- Typically, hypocellular with increased fat content .
- Special Stains and Percentage of Blasts aid in the Diagnosis .

Classification :
1 FAB Group Classification , Based on :
- The Morphological criteria of PB and BM .
- The Immunophenotyping of Leukemic cells .
- The cytochemistry of Leukemic Cells .
- For Diagnosis, Blast count in PB or BM is >30% .
2- WHO Classification :
- Molecular/Genetic Features of Malignancies .
- FAB Class. Incorporated into WHO Class.
- For Diagnosis, Blast count in PB or BM is >20% .

M0: Acute myeloblastic
leukemia with minimal
differentiation
• Most common in adult patients
• 5% of AML
• Leukocytosis in 40% and > 50% with leukocytopenia
• Diagnosis
 Less than 3% of the blasts are positive for peroxidase or the
Sudan black B reaction
 Blasts are positive for the myeloid-associated markers CD13,
CD14, CD15 or CD33, CD34 and negative for B or T lineage
marker (CD3, CD10, CD19 and CD5)
 Almost no mature myeloid cells are seen

• Morphology:
 The blasts are small to
medium-sized round cells
with an eccentric nucleus
 The nucleus has a flattened
shape
lobulated
and sometimes
or cleaved and
contain fine chromatin with
several distinct nucleoli
 The cytoplasm is lightly
basophilic without granules
 Auer rods are not found

M1: Acute myeloblastic leukemia
without maturation
• Highest incidence seen in adult and in
infants less than a year old
• 10% AML cases
• Predominant cell in the peripheral
blood is usually a poorly differentiated
myeloblast with fine reticular
chromatin and prominent nucleoli
• Auer rods are found in 50% of blasts

M2: Acute myeloblastic
leukemia with
maturation
• Presenting symptoms for M2 AML are
similar to those of the M1 type
• 30% to 45% of cases of AML
• Blasts show azurophilic granules and
Auer rods
• Evidence of maturation is present, with
>10% of the marrow cells being
promyelocytes, myelocytes,
and mature neutrophils and <20%
being monocytes

M3: Acute promyelocytic
leukemia (APML)
• Younger adults
• Median survival is about 18 months
• Fusion of a truncated retinoic acid receptor alpha (RAR-alpha)
gene on chromosome 17 to a transcription unit called PML (for
promyelocytic leukemia) on chromosome 15
• The blasts are large with abundant cytoplasm, completely
occupied by closely packed large granules, staining bright pink,
red or purple
• The nucleus is often bilobed or markedly indented with a
prominent nucleolus
• Cells containing bundles of Auer rods "faggots" randomly
distributed in the cytoplasm are characteristic, but are not
present in all cases

• Cytochemistry:
 MPO and Sudan black B are strong
positive
 PAS is negative and NSE is weak
positive
• IHC: positive for CD13, CD15, CD1
and CD33 myeloid antigens
• Cytogenetic studies: 50% cases
show translocation t(15; 17)

M4: Acute myelomonocytic
leukemia
(AMML)
• 15% to 25%
• Usually in the elderly
• Sometimes in patients who have had preceding chronic
myelomonocytic leukemia
• Both neutrophilic and monocytic cells and their precursors are
present, each constituting at least 20% of the marrow cells
• Monocytosis (≥5×10⁹/l)
• Serum and urine levels of muramidase (lysozyme) are usually
elevated because of the monocytic proliferation
• Positive reactions for Sudan black B, MPO and both specific
and non-specific esterase
• Positivity for CD13, CD33, CD11b and CD14
• inv(16) (p13; q22) and del (16)(q22)

• Morphology:
 Monoblasts: large cells with
round nuclei, one or more
prominent nucleoli and
abundant basophilic
cytoplasm, sometimes with
fine azurophilic granules,
vacuoles, and pseudopod
formation
 Promonocytes:
and
less
more
cytoplasm,
basophilic
granulated
occasional
azurophilic
nuclei are
vacuoles and
granules. The
irregular and
indented

M5: Acute monoblastic
leukemia (AMoL)
• M5a: (Acute monoblastic Leukemia)
>80% monoblasts
 Granulocyte <20% and monocytes >80%;
 Children
• M5b: (Acute monocytic leukemia)
 Granulocyte <20% and monocytes >80%; <80%
monoblasts; all developmental stages of monocytes seen
 Adults
• Serum and urinary muramidase levels are often extremely high
• Cytochemistry: NSE positive and PAS is negative
• IHC: positivity with CD11b and CD14

M6: Acute erythroid leukemias
• Erythroleukemia: 5% of AML cases
 Both erythroid and myeloid cells
 At least 50% of the nucleated cells in the bone marrow are
erythroid and at least 20% of the non-erythroid cells are
myeloblasts
 Erythroid cells are dysplastic, megaloblastoid nuclei, the
cytoplasm often possessing poorly delineated, coalescing
vacuoles
 Myeloblasts are similar to those in AML with and without
maturation
• Pure erythroid leukemia: very rare
 >80% of the marrow cells are erythroid
 Erythroblasts have deeply basophilic, often agranular,
cytoplasm may contain poorly delineated vacuoles. The nuclei
have fine chromatin and one or more nucleoli

• Howell-Jolly bodies, ring
sideroblast, megaloblastoid
and dyserythropoietic changes
• Coarse positivity of PAS
• IHC: glycophorin A

M7: Acute megakaryoblastic
leukemia (AMkL)
• Rare
• 5% of AML
• At least 50% of the blasts are from the megakaryocytic
lineage.
• The megakaryoblasts are often pleomorphic and have a
basophilic, agranular cytoplasm that may demonstrate
pseudopod and bleb formation, indicating budding
platelets
• Dysplastic platelets may be visible in the blood
• Circulating micromegakaryocytes and megakaryocyte
fragments

acuteleukemiacomplt-161017163342 (1).pptx

WHO Classification of AML
1- AML with recurrent Cytogenetic abnormalities
- usually translocation, in most cases the chromosomal
rearrangement create a fusion gene, encoding a novel
fusion protein.
I. AML with t(8;21)(q22;q22);(ETO/AML1):
- Present morphological as AML with maturation.
- The fusion protein blocks the normal function of CBF, and
induce abnormal gene activation and gene repression, this
will lead to increase proliferation with blocked
differentiation.

II. AML with abnormal B.M eosinphils
inv (16)(p13;q22) or t(16;16)(p13;q22)(CBFB/MYH11):
-Present morphology as AML with monocytic and granulocytic
maturation and presence of abnormal eosinphils in B.M.
-Combination of acute myelomonocytic leukemia (AMML) with
abnormal eosinphilis is morphologically AMML Eo.
-Abnormal immature ( basophilic ) granules in the eosinphils,
promyelocyte, and myelocyte stages.
-

III . AML with t(15;17)(q22;q12)(PML/RARa) and variants:
-it is acute promyelocytic leukemia(APL), an AML in which abnormal
promyelocyte predominate.
- The presenting signs are DIC and bleeding .
- The typical t(15;17) gene rearrangement result in the fusion of
(PML/RARa) gene and reciprocal ( RARa/PML) gene.

-PML is growth suppressor nuclear protein normally found in
complex macromolecular structure.
-The PML/RARa fusion protein leads to formation of co-repressor
complex molecules that enhance the oncogenesis of APL .

IV. AML with 11q23(MLL) abnormalities:
-These leukemia associated with monocytic features ( monoblasts
and promonocyte).
-The MLL protein is a DNA binding protein that interact with other
nuclear protein and permits the association of transcription factor
which regulate transcription.

2- AML with multilinage Dysplasia ( with or without prior MDS)
-It is an Acute leukemia ( >20% blast) with dysplasia in more
than 50% of the cells in two or more myeloid cell lines.
-It is occurs with or following MDS / MPD.
-examples of dysplasia include: hypogranular PMNs, psuedo-
pelger-Huet anomaly, megaloblastic erythrocyte, ringed
sideroblast.
- - poor prognosis.

3- AML and Myelodysplastic syndrome, therapy releated:
-These disorder arise as a result of cytotoxic chemotherapy and
/ or radiation therapy.
Two major subtypes:
I. Alkylating agent/ radiation treatment: initially it start with
MDS and eventually evolving AML.
II. Topoisomerase II inhibitor treatment.

4- Acute Myeloid leukemias not otherwise categorized:
-Include all AML cases that not fulfill criteria for any of other
described.
-The subtypes of this AML are classified according to
differentiated on morphology and cytochemical features.
I. AML Minimally Differentiated
II. AML without Maturation
III. AML with Maturation
IV.Acute Myelomonocytic leukemia (AMML)
V.Acute monoblastic leukemia and Acute monocytic leukemia
VI. Acute Erythroid leukemia (AEL)
VII. Acute Megakaryoblastic leukemia

VIII. Acute Basophilic leukemia
-The most characteristic feature by cytochemistry is metachromatic
positivity with toluindine blue.
IX. Acute panmyelosis with mylofibrosis
- it is occur with or following chemo and radio therapy.
X. Myeloid Sarcoma
- a tumor of myeloblast or immature myeloid cells occures in the
extramedullary site or in the bone.

AML
Cytogenetics & Prognosis
⚫ Favorable
t(8;21), t(15;17), inv(16)
⚫ Intermediate (Most patients)
normal, +8, +21, +22,
del(7q), del(9q),
⚫ Adverse
-5, -7, del(5q),
abnormal 3q,
complex karyotype (> 3 -
5 abnormalities)
⚫ Group CR 5 year
survival
65-75%
⚫ Favorable 91%
⚫ Intermediate 86% 40-50%
⚫
⚫ Adverse 63% <15%

AML Treatment:
Induction Chemotherapy
⚫Anthracycline (Idarubicin) for 3 daysand Cytosine
arabinoside (Ara-C) for 7 days (3+7, Younger/fit patients
only)
⚫ Supportivecare red cell and platelet transfusions,
prophylactic antibacterial, antifungals and antivirals

AML:
Response to Induction
⚫Remission status determined by bone marrow at end
of month following induction therapy (e.g. Day 14 &
28)
Completeremission:CR isdefined-
⚫Blood neutrophil count -1000/L
⚫Plateletcount 100,000/L.
⚫Circulating blasts - absent.
⚫The bone marrow <5% blasts
⚫Auerrods -absent.
⚫Extramedullary leukemia -absent

AML Treatment:
Consolidation
Following induction into Complete Remission
⚫3-4 cycles of high dosecytosinearabinoside (HiDAC)
administered approximately every 5-6 weeks
OR
⚫Bone marrow (peripheral blood stem cell) transplant
(Depends on degreeof risk)

AML-M3 or APL
⚫Acute Promyelocytic Leukemia (APL M3)
⚫Blastsand promyelocytes heavilygranulated,
Auerrods often abundant
⚫ Disseminated intravascularcoagulation (DIC)
common
⚫Treatment differs from all otherAML subtypes
once had the worstprognosis now the best
prognosis

AML-M3 or APL
⚫Treated with aderivativeof Vitamin A (all trans retinoic
acid orATRA)
⚫Favorable prognosis if diagnosed just prior tostarting
chemotherapy (>80% cured)
⚫Haschromosomal translocation, t(15;17) involving the
retinoicacid receptor- gene that blocks normal
granulocyte differentiation

Acute Lymphoid Leukemia
Malignant neoplastic proliferation and accumulation
of immature and nonfunctional Lymphoid line of
blood cells in the bone marrow
Acute lymphocytic leukemia is the most common
type of cancer in children
.

Signs and Symptoms
- Generalized weakness and fatigue
- Anemia
- Frequent or unexplained fever and infection
- Weight loss and/or loss of appetite
-Bone pain, joint pain (caused by the spread of "blast" cells
to the surface of the bone or into the joint from the
marrow cavity)
- Breathlessness
- Enlarged lymph nodes, liver and/or spleen
-Pitting edema (swelling) in the lower limbs and/or
abdomen
- Petechiae, which are tiny red spots or lines in the skin

Pathophysiology
-Damage to DNA that leads to uncontrolled cellular growth and
spread throughout the body.
-Damage can be caused through the formation of fusion genes,
as well as the dysregulation.
-This damage may be caused by environmental factors such as
chemicals, drugs or radiation.
-Some evidence suggests that secondary leukemia can develop
in individuals treated for other cancers with radiation and
chemotherapy as a result of that treatment

Initial Laboratory finding characteristic of ALL
Peripheral Blood: 1 Leukocyte count usually increased but may be normal or decreased.
2 Neutropenia
3 Lymphoblast
4 Thrombocytopenia
Bone Marrow: 1 Hypercellular
2 >20% lymphoblast ( WHO)
Other laboratory finding: 1- associated with increased cellular metabolism and turn over such:
Hyperuricemia.
incrased serum LD.
hypercalacemia due to increased BM resorption.
2 Renal failure.
3 increased CSF lymphblast.

- Terminal Deoxynucleotidyl transferase (TdT):
-- TdT, is the most important enzyme that is helpful in the
identifying cellular subtypes.
-TdT is a DNA polymerase found in cell nuclei , this enzyme not
present in the normal mature lymphocyte but can be found in
65% of the thymic population of lymphocyte.

Classification
- Based on FAB classification, ALL is categorized into three
catergories ALL-L1, ALL-L2 and ALL-L3 .
-Immunohistochemistry and immunophenotyping are
almost always necessary to distinguish ALL from AML.
-On other hand WHO identify of malignant cell as T, B and
on the degree of maturation.

FAB classification
ALL-L1
- Blasts in ALL-L1 are with high N/C ratio.
-Delicate diffuse chromatin pattern and small prominent
nucleoli.
- Scant cytoplasm .
- Affects primarily children

FAB classification
ALL-L2
-The blasts are larger than those of L1, have more plentiful
cytoplasm and are more pleomorphic.
-Abundant cytoplasm, predominant nucleoli, nuclear
clefting .
- Affects adults

FAB classification
ALL-L3 : Burkitt's type
- L3 blasts cells are fairly regular in shape with strong
basophilic cytoplasm and prominent cytoplasmic
vaculation .
Affects adults and children

FAB Classification of ALL
Morphology TdT CD10
ALL-L1 + +
Small lymphocyte scant cytoplasm;
Moderately clumped chromatin;
Inconspicuous nucleoli
ALL-L2 + +
Small and medium size lymphblast;
Mixed chromatin patterns;
Inconspicuous nucleoli
ALL-L3Burkitt- type - +/-
Large lymphblast; large nucleus with
nucleoli; cytoplasm vacuolization;
Intense cytoplasm basophilia

WHO classification
-WHO classification considers ALL and lymphblastic
lymphoma to be single disease with different clinical
presentation.
-Precursor T- and B-cell neoplasm with B.M and
peripheral blood involvement are ALL, while precursor T-
and B-cell neoplasm presenting solid tumors are
lymphoma.

WHO classification
WHO classification defines two subgroups of ALL:
1 Precursor B- and T-cell neoplasm ( leukemia/ lymphoma)
which include L1 and L2 .
2 Burkitt type ALL (L3).

WHO classification
1 Precursor B- cell leukemia:
-it is a neoplasm of lymphoblast committed to the B- cell
linage, involve B.M, peripheral blood
-some cases may present with primary involvement of
lymph node and exranodal site ( lymphoma).
-Rearrangement of immunoglobulin genes can be detected
by molecular testing.
- Additional markers of B linage commitment required for
dignosis. CD10/CD19/CD20/CD22 , TdT = +ve

WHO classification
1 Precursor B- cell leukemia:
-Cytogenetic abnormalities associated with B-ALL include
translocation, hypodiploidy, and hyperdiploidy.
- The most common is t(12;21)(p13;q22)
- Produce TEL-AML1 fusion gene.
-Hyperdiploid B-ALL have a mutation in the receptor
tyrosine Kinase FLT-3 , resulting in constitutive activation of
the receptor.
- t(1;19) PBX1-E2A , t(4;11) AF4-MLL
- Precursor B- cell has good prognosis.

WHO classification
2- Precursor T- cell leukemia:
-It is a neoplasm of lymphoblasts committed to T- cell
linage, involving B.M and peripheral blood.
-High WBC count, lymphoblast and cytochemistry similar to
B-cell, but acid phosphatase shoe intense positivity in T-
ALL.
-T- cell linage can be detected by rearrangement of the T
cell receptor genes by molecular studies.
-There are four TCR genes capable of rearranging, coding
for the a ,B, Y and & chain of the TCR.

WHO classification
2- Precursor T- cell leukemia:
-Cytogenetic studies show translocation involving
alpha and Delta TCR loci (14q11.2), the beta locus
(7q35) or gamma locus (7p14-15).
-Transcription factors.
CD2/CD3/CD5/CD7/CD10 = +ve

WHO classification
3- ALL- Burkitt type :
- Cell Large in size.
- Nuclear chromatin : fine and homogeneous
- Nuclear shape : Regular, oval to round.
- Nucleoli prominent, one or more.
- Cytoplasm amount : Moderately Abundant.
- Vaculation Often prominent.
- This tumor has a high proliferation rate and many
mitotic figures may be seen in the B.M smear.

WHO classification
3- ALL- Burkitt type :
- Burkitt's cell show clonal rearrangement of the
immunoglobulin heavy and light chain genes
All cases have translocation of the MYC gene (8q14) to
the:
1. heavy chain region on chromosome 14{t(8;14)} or
2. light chain loci on chromosome 2p12{t(2;8)} or
3. chromosome 22q11{t(8;22)}.

AML
ALL
Common in adult
Common in children
Age
Anemia, neutropenia,
thrompocytopenia,
myeloblast, Promyelocyte.
Anemia, neutropenia,
thrompocytopenia,
Lymphoblast, Prolymphcytes
Hematologic prsentation
Medium to large myeloblast
with distinct nucleoli, fine
nuclear chromatin and
abundant basophilic
cytoplasm, Auer rod can be
present
Small to medium lymphoblast,
fine chromatin with scanty to
abundant cytoplasm, indistinct
nucleoli
Prominent cell morphology
PAS negative, Peroxidase and
SBB are positive,TdT may
positive or negative
PAS and TdT are Positive,
Peroxidase and SBB are
negative
Cytochemistry

Acute Leukemia
Prognosis :
1- ALL :
- Prognosis Varies from Poor to Good According to :
1 Type of Cytogenetic abnormalities
2 Diploidy , Hyper or Hypo
3 Metastasis
Cytogenetic change Risk category
t(4;11)(q21;q23) Poor prognosis
t(8;14)(q24.1;q32) Poor prognosis
Complex karyotype (more than four
abnormalities)
Poor prognosis
Low hypodiploidy or near triploidy Poor prognosis
High hyperdiploidy (specifically, trisomy 4, 10,
17)
Good prognosis
del(9p) Good prognosis

Treatment of ALL:
• Induction phase I (4 weeks)
– Prednisone, vincristine, daunorubicin, L-asparaginase
– No benefit to adding cyclophosphamide, high-dose
cytarabine, or high-dose anthracycline
• Induction phase II (4 weeks)
– Cyclophosphamide, cytarabine, 6-mercaptopurine
• Consolidation
– 4-7 cycles of intensive multiagent chemotherapy
– Delayed reinduction

Central Nervous System Prophylaxis
• Less than 10% of ALL presents with CNS
involvement however, with no CNS prophylaxis 
CNS relapse can occur in 60% of patients.
• Risk factors for CNS involvement in adults
– mature B-cell ALL
– high serum lactate dehydrogenase levels > 600 U/L)
– presence of a high proliferative index at diagnosis ( >14% of lymphoblasts
in the S and G2/M phase of the cell cycle)
• If symptomatic CNS disease present at diagnosis 
concurrent cranial irradiation + IT chemotherapy
• For CNS prophylaxis in all other cases :
– IT-MTX and systemic high-dose MTX or some regimens
incorporate “triple” therapy ( IT MTX +ARA-
C+Corticosteroids)

care
• Cytopenias : .
– Transfusion support : Platelets and Packed red cell transfusion when necessary (
leukodepleted and irradiated to prevent GVHD)
– G-CSF Support
• Prevention of Tumor Lysis Syndrome ( Risk highest in Burkitt-ALL
and T-Cell ALL)
– Intravenos hydration 100ml/hr
– Allopurinol
– Rasburicase
– Correction of electrolyte disturbances (Hypocalcemia, Hyperphospahtemia)
• Antibiotic Prophylaxis while on aggressive chemotherapies :
– Acyclovir prophylaxis for all HSV seropositive adults
– Prophylaxis with antibiotics (quinolones) and/or antifungals during neutropenia.
– Trimtheoprim/sulfamethoxazole for PCP prophylaxis
– Ganciclovir prophylaxis for CMV seropositive patients

Adult ALL: Maintenance Therapy
• Weekly methotrexate + daily 6-mercaptopurine
– Monthly Vincristine/prednisone pulses
• Duration: 2-3 years
• Appropriate for all cases except B-cell and Ph+
ALL
• Poor outcome if omitted
• No randomized trials in adults

ALL -SPECIAL
GROUPS
• All in older adults
• Ph+ all
• Mature b-cell / burkitt- all (l3)
• T-cell all

ALL in Older Adults
• Low CR and survival rates
• Lower rate of T-cell ALL
• High rate of Ph-positive ALL ( more than 50%
of ALL in age > 65)
• Often excluded from clinical trials
• Often receive attenuated chemotherapy

Complications Observed in Older
Adults With ALL
• Comorbid conditions
• More severe mucositis related to pain medications
• Events associated with specific chemotherapies
– Vincristine: neuropathy, constipation
– Steroids: hyperglycemia, infections
– L-asparaginase: encephalopathy ( more lethargy and
somnolence occur in older adults)
• Low marrow reserve
– Adding G-CSF improves CR rate

Philadelphia Chromosome (Ph+) ALL
• t(9;22) bcr/abl translocation
• Precursor B cell
• Incidence continuously increasing with age
• Associated with very poor outcome
– No cure with intensive ALL chemotherapy (all ages).
Despite intensive chemotherapy, long term survival <
10%
– Cure with SCT possible
• Allo SCT is recommended for all patients with PH+ ALL who
achieve a CR.

Late Complications of therapy
• Late complications of therapy
• Brain tumors (cerebral irradiation)
• Secondary AML from topoisomerase inhibitors and alkylating
agents
• Cardiomyopathy (anthracyclines)
• Osteoporosis (corticosteroids)
• Growth disturbances
• Thyroid dysfunction (cranial irradiation)
• Obesity (uncertain etiology)
• Neuropsychiatric disturbances and seizures (IT MTX and cranial
irradiation)
• Emotional problems
• Discrimination with insurance, job applications and military
service

Biphenotypic Acute Leukemia
• Single population of blasts coexpressing markers of two different lineages
• Rare
• Biphenotypic acute leukemia is defined when scores are >2 for the myeloid
lineage and >1 for the lymphoid lineage
• The prognosis of biphenotypic acute leukemia patients is poor
•
• Higher incidence of CD34 antigen expression, complex
abnormal karyotype, extramedullary infiltration, relapse, and resistance to
therapy after relapse

• Standard risk
» Decreasing age (continuous variable; < 35 years)
» Decreasing WBC (continuous variable)
• < 30,000 for B-cell lineage
• < 100,000 for T-cell lineage
» T-cell lineage ( Thymic T-cell better, early T-cell is adverse risk)
» CR within 4 weeks
• High Risk: any of the following:
» High WBC at diagnosis (ie, >30,000 in B-ALL or >100,000 in T-ALL).
» Clonal cytogenetic abnormalities — t(4;11), t(1;19), t(9;22), or bcr-abl
gene positivity. The prognostic value of t(1;19) in adult ALL is less clear
than in pediatric ALL
» Time to attain CR after start of induction therapy > four weeks is of lesser
importance.
» Older age — >60 years old is high risk, 30 to 59 years old is intermediate
risk.
Prognostic Indicators

acuteleukemiacomplt-161017163342 (1).pptx

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