leukemia and lymphoma pdf - د.سلمى

Blood Diseases

Dr. Salma

“ Heamatologic

Malignancy ”

Total Lec: 40

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Pediatric Hematologic Malignancy

Dr. Salma AL-Hadad

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

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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.

Differential Diagnosis

Viral Illness?

Idiopathic Thrombocytopenic Purpura (ITP)?

Aplastic Anemia?

Leukemia?

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%

CHILDHOOD LEUKEMIA

Introduction to leukemia

Leukemia is a malignant disease characterized by unregulated proliferation of
one cell type

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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.

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

Chronic

Myeloid origin

Acute Myeloid
Leukemia (AML)
17%

Chronic Myeloid
Leukemia (CML)

Lymphoid origin

Acute Lymphoblastic
Leukemia (ALL)
80%

Chronic Lymphocytic
Leukemia (CLL)

Virtually none

Bone marrow

Normal Leukemic(ALL)

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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.

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

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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 10

Lungs:

Hypoxemia, pulmonary infiltrates

CNS: Stroke

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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

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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

CBC

WBC usually elevated, but can be normal or low

Blasts in peripheral blood

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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

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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

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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

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Asymptomatic mediastinal mass discovered by CXR

mediastinal adenopathy at presentation occurs in 60% of patients

Cough or SOB if significant compression

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,

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.

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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

Gallium Scan/ PET scan

Bone marrow biopsy

Bone scan

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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 long-term, 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.

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Contrast and compare

Hodgkin’s Lymphoma

Indolent, unifocal

Cervical, mediastinal,
supraclavicular LAD

B- symtoms common

Non-Hodgkin’s Lymphoma

Rapid (tumor lysis),
multifocal

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

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NHL(Burkitt’s subtype) Jaw Mass

NHL(lymphoblastic subtype) mediastinal LAP

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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

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Complications

Tumor related

SVC syndrome

Spinal cord compression

Pleural and pericardial effusions

Obstructive uropathy

Pharyngeal/ airway obstruction

Metabolic

Tumor lysis

Obstruction

Cytokine mediated

Cachexia, fever, malaise

Hematologic

BM infiltration

Pancytopenia

Therapy

Chemotherapy

Surgery only for abdominal emergency

Radiation for SVC obstruction, or paraspinal compression

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NHL - Treatment Response

Before Rx. After Rx.

Prognosis of Lymphomas

Overall survival 70-80%

Different sub-group survival

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