Hematological

malignancies

( )

 Tumor

2 Benign and Malignancy


4
Differentiation,Rate of growth,
Local invasion,Metastasis

Carcinogenesis
?

Differentiation Hematological
Malignant Poorly
Diff
Undifferentiation Mutation
Loss of function

Hematologic malignancies
-Hematologic spreading

-Loss of bone marrow function

- Chemotherapy

- Leukemia,Lymphoma,Myeloma

Leukemia : Pathology
Somatic mutation of marrow stem
cells

Maturation

( )
Chronic
Leukemia

(
)

Acute
Leukemia

Myelodysplastic
syndrome

1.CML:Chronic Myeloid Leukemia

- translocation chromosome
9 22
t(9;22)
- Leukocytosis Splenomegaly

-Marrow function (
)

Natural course of CML

*Chronic phase
-Leukocytosis
-Splenomegaly
*Accerelated phase: the disease is
progressing,
it behaves simalary to AML
*Blastic phase (Secondary mutation)
-Leukemic blast
-Anemia and Thrombocytopenia

 CML
*Targeted therapy (
positive)
-Imatinib(Glivec) per oral 4,000 /
10 Blastic phase
*Chemotherapy
-Hydroxyurea,Busulfan turn Blastic phase
5
*Bone marrow transplant
success 90% Chronic phase
<25% Blastic phase


Imatinib
Imatinib

-.

- 1
Cytogenic remission

* .
Chronic phase
Blastic phase

2.CLL:Chronic Lymphocytic
Leukemia

mature
lymphocytes
.
-Lymphocytosis
-Lymphadenopathy
-Organomegaly
-Hypogammaglobulinemia

 CLL

Staging
-Binet A: no organomegaly,normal RBC,plt
.
10
CLL

chlorambucil-based regimen

CLL

(autologous hematopoietic stem cell transplant)

 CLL()
-Binet B:organomegaly ,
5-7

-
- lymphocyte

50 2
- 6 .

 CLL()
-Binet C:anemia and thrombocytopenia

1-3

stage

Treatment of CLL

Aggressive

Watchful waiting:

Treatment of CLL()
*Chemotherapy
Alkylatingagents:Cyclophosphamide,
Chlorambucil
-Purine Analogue:Fludarabine
*Supportive care
-Blood Transfusion
-Prophylactic antibiotics
*Stem cell transplantation .

3.Acute Leukemia
- .
Bone marrow failure
-

Acute Leukemia

Bone marrow failure

-Aplastic anemia
-Paroxysmal nocturnal
hemoglobinuria(PNH)
-Myelodysplastic syndrome(MDS)
-Myelophthisis Solid Tumor,TB
involve Bone marrow


Paroxysmal nocturnal hemoglobinuria (PNH)
clonal

(chronic intravascular hemolytic anemia)

(deficient hematopoiesis)
(thrombosis)
(mutation) somatic


Acute Leukemia
-CBC Blast
cell(Blast>20%)BM
-BM Chromosome
prognosis
-Chromosome study=Cytogenetic
study

Chromosome
study=Cytogenetic study

-(polymerase chain reaction : PCR)

DNA

PCR for Rara gene
PML-RARA APL
-(fluorescence in situ hybridization : FISH)

donor recipient

 Acute
Leukemia

-Anemic symptom
-Leukopenia,Neutropenia(PMN<1,500)
Increased risk of infection
Thrombocytopenia(plt<100,000):blee
ding


16
.MDS

6 10

Step
Leukemia

-
-prognosis



-Primary(Leukemia
mutationcell)
-Secondary(Therapy
related,MDS)

-Morphology:Wright stain
-Immunophenotype:Antigen
cell(Flow cytometry)


-Mutation
Targeted Therapy
-Mutation
Prognosis

-Chemo
-BMT
-Supportive:Blood


1.Remission Induction BMFail
60-80%
.
Pancytopenia D7-D21
Recovery D28-D35
Chemo
Blast>Normal
BM

Cell
Remission Blast<5%

Cell Blast

 ()
2.Post Remission:Cure
-
-
Type, Cytogenetic
information
and Host(Performance status,Health
condition)

ALL,AML
2 lymphocyte myeloid
Acute lymphocytic leukemia (ALL)
lymphocyte
Acute Myeloid Leukemia(AML (ANLL))

non-lymphoid cells

( differentiation)

myeloblasts,promyelocytes, myelomonoblasts,
monoblasts, erythroblasts megakaryoblasts

 2
lymphocyte myeloid

THE PROGENITOR BASIS OF HEMATOPOIESIS

4.MDS
Hematopoietic stem cells Mutation
cell

Acute Chronic

Marrow Fail,Require frequent

transfusion
Worsening course Turn

5.Lymphoma
Tumor of Lymphoid Tissue
Hodgkins disease

- Reed sternbergs
cell
-
Nodal
-
-

Non-Hodgkins
disease

-Tumor
Lymphocyte
B-cell,T-cell
-
Nodal
Extra Nodal
-Systemic spreading


Nodal
-Lymph node
:Cervical,Axillary,Epitrochler,Ing
uinal,Femoral
-Spleen
Extranodal
-Skin,Brain,Aerodigestive
tract,Liver,Bone marrow
**


Classification

Staging

- NHL

Hodgkins
-

Disease
Targeted Therapy
-

Classification of NHL
Grade

Cell Type

-Low grade

-B cell

-Intermediate grade

-T cell

-High grade

Staging
Stage I:One lymph node group
Stage II:More than one lymph node group
same side of diaphragm
Stage III:Both side of diaphragm
Stage IV:Systemic involvement of nonlymphoid organ

(B symptoms=,.,night sweating)

Chemo:CHOP,Salvage regimen
Targeted Therapy
Combined:R-CHOP
RT

 Rituximab
DLBCL(CD 20+ve)
. HIV positive,
uncontrolled infection
Lung complication
Anaphylactic reaction

6.Multiple myeloma
Malignant Plasma Cells
Monoclonal
Immunoglobulin(M Protien)
BM Plasma cell
Marrow effect:Anemia
Skeleton effect:Osteoclast(Hypercalcemia)
osteolytic lesion
Spinal cord compression
Immunoglobulintubular toxicity
Interstitial nephritis

Treatment of MM
Chemo:Melphalan,Velcade
New therapy
:Thalidomide,Lenolidomide
immunomodulatory agent anti-angiogenic
500
:Bortezomib Proteasome inhibitors

proteasomes

BMT-Autologous


MM

-CR
-VGPR
BMT
Induction MP
Velcade,BortezomibDexa,Thalidomide-Dexa
responseBMT