Transcript Leukemia? - muhadharaty.com

Pediatric Hematologic Malignancy
th
5 Year Medical Students
Dr. Salma AL-Hadad
April 12th 2016
Objectives
To list the most common pediatric malignancies
Define leukemia and lymphoma & list their
classifications
To list the signs and symptoms of leukemia and
lymphoma
To outline the steps for diagnosis of leukemia and
lymphoma
Epidemiology
Pediatric cancer is rare - 2% of all cancer
Most often occur before 15 years of age
Accounts for 10% of childhood deaths
Most common cause of death from disease
Second to accidents
Leukemia, Lymphoma and CNS Tumors are the most
common
Predisposing Factors
Genetic
Syndromes (trisomy 21), bone marrow failure
Hereditary
Wilms Tumor, Retinoblastoma
Environmental
Radiation, toxins
Case Study
5 year old girl presented with 1 week history of fatigue,
pain that began in her feet and progressed to legs; and a
petechial rash over her arms and legs with some bruising.
She had a brief episode of epistaxis one day prior to
appointment.
They also felt that her abdomen is prominent for the past 2
weeks.
Case Study
Differential Diagnosis
Viral Illness?
Idiopathic Thrombocytopenic Purpura (ITP)?
Aplastic Anemia?
Leukemia?
Case Study
Initial labs at admission:
CBC
Hb: 4.9 g/dl (11.5-13.5)
Platelets: 6,000/cmm (150,000-400,000)
WBC: 27,000/cmm
Blasts: 34%
Neutrophils 1%
Introduction to leukemia
Leukemia is a malignant disease characterized by unregulated
proliferation of one cell type
Leukemias are classified into 2 major groups
Chronic in which the onset is insidious, the disease is
usually less aggressive, and the cells involved are usually
more mature cells
Acute in which the onset is usually rapid, the disease is
very aggressive, and the cells involved are usually poorly
differentiated with many blasts.
Introduction to leukemia
Both acute and chronic leukemia are further classified
according to the prominent cell line involved in the
expansion:
If the prominent cell line is of the myeloid series it is a
myelocytic leukemia
If the prominent cell line is of the lymphoid series it is a
lymphocytic leukemia
Classification of leukemia
Acute
Myeloid
origin
Lymphoid
origin
Chronic
Acute Myeloid
Leukemia (AML)
17%
Chronic Myeloid
Leukemia (CML)
3%
Acute Lymphoblastic
Leukemia (ALL)
80%
Chronic Lymphocytic
Leukemia (CLL)
Virtually none
Bone marrow
Normal
Leukemic (ALL)
ALL
naïv
e
B-lymphocytes
Lymphoid
progenitor
T-lymphocytes
AML
Hematopoietic
stem cell
Myeloid
progenitor
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Plasma
cells
Introduction to leukemia
Leukemic proliferation, accumulation, and invasion of
normal tissues, including the liver, spleen, lymph nodes,
central nervous system, and skin, cause lesions ranging
from rashes to tumors.
A humoral mediator from the leukemic cells may inhibit
proliferation of normal cells.
Failure of the bone marrow and normal hematopoiesis
may result in pancytopenia with death from hemorrhage
and infections.
Introduction to leukemia
The lab diagnosis is based on two things
Finding a significant increase in the number of
immature cells (blasts), >30% blasts is diagnostic
(normally <5%)
Identification of the cell lineage of the leukemic cells
Clinical manifestations
Symptoms due to:
 Marrow failure
 Tissue infiltration
 Leukostasis
 Constitutional symptoms
 Other (DIC)
Usually short duration of symptoms
Marrow failure
Neutropenia:
Infections, sepsis
Anemia:
Fatigue, pallor
Thrombocytopenia:
Bleeding
Enlargement of liver, spleen, lymph nodes
Gum hypertrophy
Bone pain
Other organs: CNS, skin, testis, any organ
Leukostasis
Accumulation of blasts in microcirculation with impaired
perfusion
 Only seen with WBC > 50 x 109/L
Lungs:
Hypoxemia, pulmonary infiltrates
CNS:
Stroke
Diagnosis: Symptoms
Fatigue
Pallor
Anorexia
Bruising/Bleeding
Fever
Bone/joint pain
Diagnosis: Exam Findings
 Pallor
 Bruises & Petechiae
 Lymphadenopathy
 Hepatosplenomegaly
 Cranial Nerve Palsies
 Testicular enlargement
 Chloromas & Leukemia Cutis
 Mediastinal Mass
 Superior Vena Cava Syndrome
Leukemia Cutis
Petechiae
Gum hypertrophy
Differential Diagnosis
Viral Illness
lymphadenopathy
ITP
bleeding tendency
Aplastic Anemia
anemia and bleeding tendency
Arthritis
Joint swelling
SLE
Joint swelling
Diagnostic Studies
Complete Blood Count
Bone marrow aspirate:
 Morphology & Immunohistochemistry examination
using FAB classification: ALL L1-L3, AML M0-M7
 Flowcytometry
 Cytogenetics
Diagnostic Studies
CBC
WBC usually elevated, but can be normal or low
Blasts in peripheral blood
Normocytic anemia
Thrombocytopenia
Neutropenia
Laboratory tests:
To detect infiltration of the disease; CXR, CSF,
Ultrasound for kidney
To assess the function of other organs; LFT, RFT, viral
titers, LDH, uric acid
Auer rods in AML
ALL
Principles of treatment
Combination chemotherapy
 First goal is complete remission,
 Further treatment to prevent relapse
Supportive medical care
 transfusions, antibiotics, nutrition
Psychosocial support
 patient and family
Prognosis
Leukemia is now a curable disease in developed world
ALL
80% - 90%
AML
65%
Childhood lymphoma
Lymphomas are malignant neoplasms of lymphoid
lineage.
Major types include Hodgkin's and Non-Hodgkin's
lymphoma
60% are Non-Hodgkin's lymphoma (NHL)
40% Hodgkin’s Lymphoma (HL)
Hodgkin’s lymphoma
Six year old boy presented with painless right sided
cervical swelling
not responding to antibiotics
How do they present?
Clinical Presentation
 The onset is typically subacute & prolonged for HL
 Most common presentation in children is asymptomatic cervical
lymphadenopathy in 90% of cases
 Painless, firm or rubbery, not inflammatory
 Extension from one lymph node group to another
 Asymptomatic mediastinal mass discovered by CXR
 mediastinal adenopathy at presentation occurs in 60% of
patients
 Cough or SOB if significant compression
Clinical Presentation
Systemic symptoms, classified as B symptoms
Unexplained fever >39°C
Weight loss >10% total body weight over 3 months
Drenching night sweats
Infrequently presents as axillary or inguinal adenopathy
Case Study
A 13-y-old boy presented with malaise, night sweats, loss of weight
and intermittent fever dating from a flu-like illness 3 months ago.
O/E, he had bilateral, cervical & axillary LAP; the glands were 2-5cm
in diameter, firm, rubbery, discrete and fairly mobile. His liver and
spleen were not enlarged.
Investigation showed that his hemoglobin was low (11.3g/dl) and the
WBC was normal but his ESR was 78mm/h; the blood film did not
show any abnormal cells.
No enlargement of the hilar glands was seen on chest X-ray,
Case Study
A cervical L.N. was removed for histology: the tissue
consisted of giant cells known as Reed-Sternberg cells. These
large binucleated cells are characteristic of Hodgkin's
disease.
A BM examination was normal and CT showed no
involvement of other lymph nodes.
This patient had stage IIB Hodgkin's disease.
In view of his symptoms, the suffix 'B' was added to the
stage.
Diagnostic Workup
Tissue is needed for definitive histologic diagnosis
Sample the node that is most accessible
Labs needed for evaluation (not for diagnosis)
CBC with blood film
ESR
LFT, Renal function
Alkaline phosphatase; ferritin,copper elevated
Immune response decreased,
Cytokines IL 1,6,TNF, IL 2 elevated - B symptoms,
Diagnostic & Staging Workup
Cervical area US/CT/MRI
Thoracic imaging
Chest X-ray, CT scan of chest (ant/middle mediastinum)
for best visualization of lung parenchyma, pleura
Abdominal imaging
US/CT/MRI
Diagnostic & Staging Workup
Gallium Scan/ PET scan
Bone marrow biopsy
Bone scan
HL Histology
The pathologic hallmark of HD
is the identification of Reed –
Sternberg cells in tumor
tissue.
 Reed-Sternberg cells are giant
binucleated cells with
prominent nucleoli, classically
a single giant nucleolus in
each nucleus
Hodgkin’s Disease Treatment
Balance ensuring the best opportunity for longterm, disease free survival and the lowest risk of
severe treatment toxicity
With appropriate treatment about 85% of patients
with Hodgkin’s disease are curable with
Combination Chemo + Radiotherapy
NHL Clinical Presentation
 Depend primarily on pathological subtype and sites of
involvement.
 70% present with advanced stages III or IV including extra nodal
disease as GIT, bone marrow, and central nervous system (CNS)
involvement.
 Burkitt’s Lymphoma (B-Cell) commonly presents with abdominal
or head and neck masses with involvement of the bone marrow
or CNS.
 Lymphoblastic Lymphoma (T Cell) commonly presents with an
intra thoracic or mediastinal mass, and may spread to the bone
marrow and CNS.
Contrast and compare
Hodgkin’s Lymphoma
Non-Hodgkin’s Lymphoma
 Indolent, unifocal
 Rapid (tumor lysis),
multifocal
 Cervical, mediastinal,
supraclavicular LAD
 B- symtoms common
 Abdominal, mediastinal
masses and LAD
 Abdominal pain common
 Intussusception
High Risk for NHL
Familial cases
Inherited immune deficiencies
Acquired immune deficiencies: HIV, organ
transplant, post-BMT
EBV
malaria
Chemicals: Pesticides and solvents
NHL(Burkitt’s subtype) Jaw Mass
NHL(lymphoblastic subtype) mediastinal LAP
Diagnosis
Lymph node or tissue biopsy is mandatory for histologic
diagnosis for appropriate:
 Immunohistochemical,
 Molecular studies,
 Culture,
 Cytogenetic analysis
Diagnostic Evaluation
 Complete history and physical examination
 Complete blood count with differential count, ESR
 Chemistries: renal and hepatic function tests, serum electrolytes
 Serum lactate dehydrogenase(LDH) and uric acid; alkaline
phosphatase
 Imaging studies: CXR, computed tomography (CT) of neck and
chest, CT, etc.
 Bone marrow examination
 Cerebrospinal fluid examination (cytology)
Treatment Options
Supportive
Chemotherapy
multi-agent
intensive
Radiotherapy in special cases
Complications
 Tumor related
SVC syndrome
Spinal cord compression
Pleural and pericardial
effusions
Obstructive uropathy
Pharyngeal/ airway
obstruction
 Metabolic
Tumor lysis
 GI
Obstruction
 Cytokine mediated
Cachexia, fever, malaise
 Hematologic
BM infiltration
Pancytopenia
Therapy
Chemotherapy
Surgery only for abdominal emergency
Radiation for SVC obstruction, or paraspinal
compression
NHL - Treatment Response
Before Rx.
After Rx.
Prognosis of Lymphomas
 Overall survival 70-80%
 Different sub-group survival
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