1.

General approach to anemia. Dalam : McPhee, Stephen J. Papadakis, Maxine A.

Current Medical Diagnosis and Treatment. The McGraw Hills Companies. 2011
2. Alwi Idrus et al. Penatalaksanaan di Bidang Ilmu Penyakit Dalam. InternaPublishing.

2019

LEUKEMIA

Etiology:
• Radiation
• Viral infection (Epstain-Barr Virus)
• Chemical à benzene, chemotherapeutic agent (cyclophosphamide, melphalan, etoposide)
• Gene mutation

• Smoking

Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Chronic Lymphoblastic Leukemia
(AML) (ALL) (CML) (CLL)


* Fast growing cancer of myeloid
progenitor
* Fast growing cancer of Lymphoblast
progenitor * Markedly left-shifted myeloid series but
with low percentage of promyelocytes
* The disease is usually indolent with
slowly progressive accumulation of long-
* Primarily an adult diseases (median: 60 * 80% of the acute leukemia of childhood lived small lymphocytes
years)
* One subtype of AML à Acute
(peak incidence 3-7 y.o)
* 2 types of ALL
and blast
* CML is a disorder of middle age
* CLL is disease of older patients, with
90% of cases occurring after age 50 years
Promyelocytic Leukemia (APL) - B cell (B-ALL) à Mature B-ALL (Burkitt
Leukemia) same as Burkitt lymphoma (a
(median: 55 years)

(median: 70 years)

type of non-Hodgkin lymphoma)
- T cell (T-ALL) à can cause an enlarged

thymus

* Most patients have been ill only days or weeks
* Anemia à fatigue, weakness, shortness of breath, pale * Fatigue
* Night sweats
* Infection is due to neutropenia
* Hyperleukocytosis à gum hypertrophy, headache, confusion, dyspnea * Low grade fever
* Patients may also complain of abdominal fullness related to splenomegaly
* Trombocytopenia à gingival bleeding, epistaxis, menorrhagia, petechiae, purpura * Sternal tenderness may be present as a sign of marrow overexpansion
* There is variable enlargement of the liver, spleen, and lymph nodes * Rarely, the patient will present with a clinical syndrome related to leukostasis with blurred vision,
* Bone tenderness may be present, particularly in the sternum, tibia and femur respiratory distress, or priapism

* 80% of patients will have
lymphadenopathy

* CBC à Pancytopenia
* CBC à The hallmark of CLL is isolated
* CBC à Elevated white blood count,
* Blood clotting tests (PT, PTT, fibrinogen)
* Hyperuricemia may be seen (uric acid is released by cell when DNA breaks down)
usually not anemic, platelet count may be
lymphocytosis. WBC is usually >
20,000/mcL. The hematocrit and platelet
normal or elevated
* Bone marrow tests à > 20% blasts in the bone marrow
* Blast in peripheral blood in 90% of patients (blast may be absent from the peripheral smear in as * Peripheral blood: The myeloid series is
left shifted, with mature form dominating
count are usually normal.
* Peripheral blood smear à About 95% of
many as 10% of cases “aleukemic leukemia”)
* Immunophenotyping (uses antibodies to detect the presence or absence of WBC antigens) * Bone marrow test: hypercellular,
myeloblasts comprise < 5% of marrow
the circulating cells are lymphocytes that
appear small and mature.
1. Flow cytometry * Bone marrow à infiltrated with small
2. Immunohistochemistry cells

lymphocytes > 30%
* Cytogenetic

* Flow cytometry:
the phenotype of AML cell usually express
* Flow cytometry:
- B cell ALL will express CD19, and most
* Cytogenetic:
The hallmark of the disease is that the
* Immunophenotyping:
CLL demonstrates coexpression of the B
myeloid antigens such as CD13 or CD33

cases will express CD10
- T cell ALL will express some combination BCR/ABL gene (Philadelphia
chromosomes) is detected by the PCR
lymphocyte lineage marker CD19 with the
T lymphocyte marker CD5
* Histochemistry:
The FAB (French, American, British)
of CD 2,5, and 7
- Almost all ALL cells express terminal

classification of AML based on morphology deoxynucleotidyl (TdT)

and histochemistry à M0 until M7

* Peripheral blood smear:
Smudge cells also known as “basket cells”



are ruptured CLL B-cells because low of
protein vimetin. Patients with a high

* Peripheral blood smear:
The Auer rod (arrows) an eosinophilic .
percentage of smudge cells (eg, low
vimetin) experience a prolonged time to

needle-like inclusion in the cytoplasm of
myeloblast, is pathognomonic of AML, if first treatment.

seen, secure of diagnosis

* Cytogenetic: * Cytogenetic:
* Cytogenetic:
APL à characterized by chromosomal
translocation t(15;17), which produces the
- B cell ALL à t(8;14), t(2;8), and t(8;22)
- Better prognosis: hyperdiploidy (> 50 - Unfavorable: deletions of chromosome
17p or 11q
fusion gene PML-RAR alpha

chromosomes)
- Unfavorable: Philadelphia chromosome - Favorable: deletions of 13q

t(9;22) and t(4;11)

1. Induction chemotherapy with cytarabine 1. Adult with ALL are treated with combination 1. Extreme hyperleukocytosis (priapism,
100 mg/m2 iv for 7 days and daunorubicin chemotherapy, including daunorubicin,
1. The initial treatment of choice is the
respiratory distress, viasual blurring,
45-60 mg/m2/day iv for 3 days (7+3) vincristine, prednisone, and asparaginase
combination of the chemotherapeutic
altered mental status) à emergent
2. Postremission à High dose cytarabine and agent fludarabine plus the antibody
2. High risk patients (Philadelphia leukapheresis is performed in conjunction
Hematopoetic Stem Cell Transplantation rituximab, with or without the addition
chromosome, hyperleukocytosis, failure to with myelosuppresive therapy
(HSCT) autologous and allogeneic of the chemotherapeutic drug
get complete remission in 4 weeks) with 2. Imatinib mesylate (400 mg PO/day) or
3. APL à Induction therapy should include an cyclophosphamide.
adverse cytogenetics or poor responses to dasatinib (100 mg/day) specially inhibits
anthracycline (daunorubicin or idarubicin) 2. Chlorambucil 0,6-1 mg/kg orally every 3
chemotherapy are best treated with the tyrosine kinase activity of the bcr/abl
plus all-trans-retinoic acid weeks for approximately 6 months, was
allogeneic transplantation. Autologous oncogene
standard treatment prior to the
transplantation is a possibility in high risk 3. The only proven curative therapy for CML is
development of fludarabine.
patients who lack a suitable donor. allogeneic bone marrow transplantation