Hematological malignancies

(Leukemia and MDS)

By
D r I b t e s am M K h a lifa
A s s is tant p ro f e ssor o f in t e r n al m e d ic in e a t F C M S .
SLOs:
By the end of this lecture students should be able to:
•Recognize Definition, predisposing factors, etiology of MDS.
•Discuss Pathogenesis and clinical features of MDS.
•Understands Diagnosis and management of MDS.
•Recognize definition, epidemiology, etiology, pathology and pathogenesis of Leukemia.
•Describe clinical picture and classification of leukemia.
•Outline management of all types of leukemia.
Classification
•Acute leukemia (ALL , AML).
•Myelodysplasia (pre- malignant).
•Lymphoma (Hodgkin and non- Hodgkin lymphoma either T cell or B cell).
•Chronic leukemia (CLL, CML).
•Myeloproliferative neoplasm (MPN) and myelofibrosis.
•Multiple myeloma.
Acute leukemia
• A cu te lymp h o bla stic le u k e mia .
• A cu te mye lo b la stic le u k e mia .
• Ch r o nic lymp h o cytic leu k emia.
 Case scenario (1)
•A 14-year-old boy is brought to the physician by his family
because of a 2-week history of generalized fatigue, intermittent
fever, and occasional bleeding from his nose.

•On examination, his temperature is 38.3°C. He appears pale.

Physical examination shows cervical lymphadenopathy and
multiple petechiae on his trunk. The spleen is palpated 3
cm below the left costal margin.

•Laboratory results revealed, hemoglobin concentration is 9.3

g/dL, leukocyte count is 63,000/mm3, and platelet count
is 30,000/mm3. A bone marrow aspirate predominantly
shows immature leukocytes that is shown in the figure which
stained negative for myeloperoxidase.

•What is your differential diagnosis and why?

Acute leukemia
•It is malignant proliferation of bone marrow blast
cells.
•Clinical symptoms occur due to bone marrow failure
(anemia, neutropenia and thrombocytopenia) as a
result of bone marrow infiltration by malignant cells
(> 20% blasts in BM).
•It may occur at any age but There are four main
subtypes, as discussed above:
Acute myeloid leukemia (AML) more common in
adults and old age.
Acute lymphoblastic leukemia (ALL): more
common in children
 Clinical features of acute leukemia:
Manifestations are mainly due to bone marrow failure and various tissue infiltation

Manifestations of bone marrow failure: Manifestations of tissue infiltration:

•Fever due to infections (neutropenia). • Bone: Painful tender sternum.

•Anemia. • Hepatosplenomegaly and lymphadenopathy.

• Skin: leukemia cutis.

•Bleeding (thrombocytopenia).
• Nervous system: infiltration of meninges with headache
and cranial nerve paralysis.

• Retina: diminished vision.

• Porta hepatis: obstructive jaundice.

• Leukostasis with thrombotic insults.

• Serous membrane: effusions.

• Kidney tubular disorder.

Classification of acute leukemia:
FAB classification of AML. FAB classification of ALL.
•M0: Undifferentiated. •L1: cells are small and homogenous
population.
•M1: Myeloblastic without maturation.
•L2: cells are large and heterogenous.
•M2: Myeloblastic with maturation.
•L3: Burkitt like large cells, vacuolated
•M3: Promyelocytic. cytoplasm (aggressive type).
•M4: Myelomonocytic.
•M5: Monocytic or monoblastic.
•M6: Erythroleukemia.
•M7: Megakaryoblastic.
Investigations:
•CBC with differential will show:
TLC is variable.
Anemia.
Thrombocytopenia.
Peripheral blood blast in blood film.
•Bone marrow aspirate: Infiltraton by >20% blast (presence of Auer rods in the cytoplasm of malignant
cells and positivity for MPOX indicate a myeloid type).
•Immunophenotyping for determining type of leukemia.
•Cytogenetics and FISH study for therapeutic and prognostic assessment.
•Other investigations: serum uric acid, LDH, renal and hepatic profiles, MRI brain, PAUS, ECHO.
 Management
Untreated acute leukemia is invariably fatal.
risk stratification for all patient is a must to determine appropriate plan of management.

Treatment with curative intent: Palliative therapy:

•May be successful, or may fail, either because •Every attempt should be made to ensure that
Leukemia refractory to treatment. the patients are at home as much as possible,
while making available the full range of
Disease relapse. supportive care.
Treatment-related mortality.
•Since curative treatment carries considerable
•Palliation may well include low-dose
morbidity and potential mortality, it is essential
chemotherapy in addition to blood product
for the ‘risk/benefit’ ratio to be clearly
understood by physician and patient alike. support and antimicrobials.
Active therapy:
Supportive care
This forms the basis of treatment, whether for cure or palliation:
Avoidance of symptoms of anemia (Hb >80–100 g/L): Repeated transfusion of irradiated packed
RBCs is needed.
Prevention or control of bleeding (platelet count <10 × 109 /L in the stable patient and <20 ×109 /L in
the septic patient, or <50 × 109 /L if a procedure is planned, e.g. lumbar puncture).
Correction of coagulation abnormalities. This is achieved with fresh frozen plasma (FFP) to keep the
activated partial thromboplastin time ratio and INR <1.5 times normal.
Treatment of infection: Education of patients, relatives and staff about diet, hand washing and
isolation facilities is necessary. Selected prophylactic antibiotics, antifungals, antivirals are required.
Control of hyperuricemia: This should be achieved with hydration, prophylactic allopurinol and
occasionally Rasburicase.
Specific treatment
Details are determined by the type of leukemia and by the patient's risk
factors and tolerance of treatment.

•Induction chemotherapy: The initial requirement of therapy to achieve complete remission.

•Consolidation chemotherapy: Successful remission induction is always followed by.

•Maintenance chemotherapy: in patients with ALL

•Stem cell transplantation: Allogeneic hematopoietic stem cell transplantation

Back to our case…
Identify the prognosis of the case?
Identify his response criteria?
Prognosis:
•Acute leukemia is fatal
without treatment but
with treatment the
prognosis depends on
age, type of disease,
TLC and cytogenetic
analysis.
Acute leukemia:
Myelodysplastic syndrome (MDS)
Myelodysplastic syndrome (MDS).
•It is a pre-leukemic disease and represent genetic steps in the development of
leukemia.
•It is characterized by progressive bone marrow failure with quantitative and
qualitative abnormalities in at least one of the three myeloid cell lines (red cells,
granulocyte/monocytes and platelets).
•Presents with symptoms of:
Anemia.
Infection or bleeding due to pancytopenia.
MDS should be suspected in patients with otherwise unexplained cytopenia or
macrocytosis.
 Investigations:
•(CBC): Serial blood counts show evidence of increasing bone marrow failure with anemia,
neutropenia and thrombocytopenia, either alone or in combination.

•Blood film: Characterized by cytopenia and abnormal-looking (dysplastic) blood cells, including
macrocytic red cells and hypogranular neutrophils with nuclear hyper- or hyposegmentation.

•Bone marrow: Hypercellular, with dysplastic changes in at least 10% of cells of one or more cell
lines. Blast cells may be increased but do not reach the 20% level that indicates acute leukemia.
•
•Chromosome analysis: frequently reveals abnormalities, particularly of chromosome 5 or 7.
Prognosis
•The natural history of MDS is progressive worsening of dysplasia leading to fatal bone marrow
failure or progression to AML in 30% of cases.

•The time to progression varies (months to years) with the subtype of MDS, being slowest in MDS
with ring sideroblasts and single-lineage dysplasia and most rapid in MDS with excess blasts.

•The median survival for low-risk patients (IPSS-R very low and low) is 5–9 years, that for the
intermediate group is 3 years and that for high-risk patients (IPSS-R high and veryhigh) is 1–1.5
years.
Management:
Treatment options include the following: Hypomethylating agents (e.g. azacitidine).
Supportive care is the mainstay for all patients Immunomodulators.
with MDS and symptomatic low blood counts.
and the prevention and treatment of MDS- Intensive chemotherapy; in selected patients
associated bleeding and infection. with high-risk MDS.

Erythropoietin can be used in selected patients Lenalidomide.

with low-risk MDS, symptomatic anemia and Allogeneic SCT offers the hope of cure for
inappropriately low endogenous EPO levels. carefully selected MDS patients who have a
Iron chelation should be considered for patients matched donor.
with good prognostic MDS who develop
secondary iron overload (transfused with more
than 20 units of red cells or serum ferritin>1000
μg/L).
 Home messages:
• Acute lymphoblastic leukemia (ALL): It is the most common leukemia in pediatrics, accounting for up to 80% of cases
in this group vs. 20% of cases in adults. Treatment among young adults is predominantly inspired by pediatric regimens
with better survival rates.

• Acute myelogenous leukemia (AML): AML is characterized by greater than 20% myeloid blasts and is the most
common acute leukemia in adults. It is the most aggressive cancer with a variable prognosis depending upon the
molecular subtypes.

• Chronic lymphocytic leukemia (CLL): CLL occurs from the proliferation of monoclonal lymphoid cells. Most cases
occur in people between ages 60 and 70.

• Chronic myelogenous leukemia (CML): CML typically arises from reciprocal translocation and fusion of BCR on
chromosome 22 and ABL1 on chromosome 9, resulting in dysregulated tyrosine kinase on chromosome 22 called the
Philadelphia chromosome. This, in turn, causes a monoclonal population of dysfunctional granulocytes, predominantly
neutrophils, basophils, and eosinophils
References:
•Ralston, Stuart H., et al., editors. Davidson's Principles and Practice of Medicine. 23rd ed.,
Elsevier Health Sciences, 2018. pages (954-960).

•Kumar and Clark's Clinical Medicine, 8th e (Kumar, Kumar and Clark's Clinical Medicine) by
Parveen Kumar CBE BSc MD DM (HC) FRCP FRCP(Edin), Michael L Clark MD FRCP.
 Brain storming:
A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On
examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His
spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a
leukocyte count of 81,000/mm3, and a platelet count of 35,000/mm3. A peripheral blood smear
shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic
inclusions. Which of the following is the most likely diagnosis?
a. Myelodysplastic syndrome
b. Chronic lymphocytic leukemia
c. Acute lymphoblastic leukemia
d. Acute myelogenous leukemia
e. Chronic myelogenous leukemia
f. Hairy cell leukemia
 Brain storming:
•A 3-year-old boy is brought to the physician by his mother because of a 2-week history of generalized
fatigue, intermittent fever, and occasional bleeding from his nose. His temperature is 38.3°C (100.9°F).
He appears pale. Physical examination shows cervical lymphadenopathy and multiple petechiae on his
trunk. The spleen is palpated 3 cm below the left costal margin. His hemoglobin concentration is 9.3
g/dL, leukocyte count is 63,000/mm3, and platelet count is 30,000/mm3. A bone marrow aspirate
predominantly shows immature leukocytes that stain negative for myeloperoxidase. Which of the
following is the most likely diagnosis?
a. Hodgkin lymphoma
b. Hairy cell leukemia
c. Acute myelomonocytic leukemia
d. Pre-B-cell acute lymphoblastic leukemia
e. Acute megakaryoblastic leukemia
f. T-cell chronic lymphocytic leukemia
Thank you…