Leukemia

Question 1

What is acute myeloid leukemia

Answer 1

• Heterogeneous group
• Aggressive blood cell cancers
• Arise from malignant hematopoietic precursor cells in bone marrow
• Leukemic cells interfere with production of normal blood cells

Question 2

Underlying causes and pathogenesis of AML

Answer 2

Underlying Causes
• Associated with environmental factors
• Chemical exposure, radiation, tobacco, etc.
• Manifest from other disorders
• MDS
• Myeloproliferative neoplasms
• Paroxysmal nocturnal hemoglobinuria
• Aplastic anemia
• Clonal hematopoiesis of indeterminate prognosis (CHIP)
• Inherited genetic abnormalities
• Pathogenesis
• Malignant transformation of myeloid precursor cells
• Results abnormal cells proliferation
• Blocked in ability to differentiate into mature blood cells
• Self-renewing leukemic stem cells

Question 3

AML s/s

Answer 3

Signs & Symptoms
• Related to anemia
• Excess bleeding
• Bruising
• Infections
• Headache or focal neurologic complaints

Question 4

AML physical findings

Answer 4

Physical Findings
• Pallor, bleeding, or bruising
• Hepatomegaly
• Splenomegaly
• Soft tissue mass

Question 5

AML lab findings

Answer 5

• Laboratory
• CBC: decreased mature RBCs, neutrophils, and/or platelets, leukocytosis
• CMP: Tumor lysis syndrome (induction of therapy)
• Leukemic blasts in peripheral blood, bone marrow, and/or other tissues
• Manifest as Auer rods

Question 6

AML complications

Answer 6

Pancytopenia
• Result of underlying disease or its treatment
• Hyperleukocytosis/leukostasis
• Respiratory and/or neurologic distress
• Myeloblasts >50,000/microL
• Any patient with AML & myeloblasts >100,000/microL
• Metabolic abnormalities
• Tumor lysis syndrome
• Hyperkalemia, hyperphosphatemia, hyperuricemia, and/or renal insufficiency
• Severe thrombocytopenia/coagulation disorders
• Bleeding
• Disseminated intravascular coagulation (DIC)

Question 7

AML diagnostics

Answer 7

emergencies
• Diagnosis
• Infiltration of bone marrow or peripheral blood by ≥20% blasts
• Characteristic features
• Morphology, cytochemical, immunophenotypic & cytogenetic
• Presence of myeloid sarcoma or specific chromosomal and/or molecular abnormalities
• AML Classification System
• Morphology
• Immunophenotype
• Karyotype
• Molecular features

Question 8

AML treatment plan

Answer 8

Referred urgently for expert evaluation & management
• Consult Oncology
• Treatment of AML
• Medically fit adults
• Intensive remission induction chemotherapy
• Unable to tolerate intensive remission induction therapy
• Lower intensity therapy
• Less toxicity
• Small probability of achieving remission
• Bone marrow aspirate & biopsy
• 7 to 10 days after completion of induction chemotherapy
• Adequate elimination of leukemic cells
• Following recovery of neutrophils & platelets
• Consolidation therapy
• Intensive treatment
• Follows after remission
• Chemotherapy
• Autologous hematopoietic cell transplantation (HCT) or allogeneic HCT
CHRONIC LYMPHOCYTIC

Question 9

What is chronic lymphocytic leukemia

Answer 9

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
• Mature B cell neoplasm
• Progressive accumulation of monoclonal B lymphocytes
• Indolent cancer
• CLL cancer cells found mostly in blood & bone marrow
• SLL cancer cells found mostly in lymph nodes
• Both are types of non-Hodgkin lymphoma
• Epidemiology
• Most common leukemia in adults in Western countries
• 25-35% of all leukemias in USA
• Considered to be disease of older adults
• Median age at diagnosis ~70 years
• Incidence increases rapidly with increasing age
• More common in men
• Varies by race & geographic location
• Genetics most likely explanation
• No discernible occupational or environmental risk factors

Question 10

S/s of CLL

Answer 10

Signs & Symptoms
• Most patients feel entirely well
• Routine blood count reveals absolute lymphocytosis
• Leads to CLL diagnosis
• Painless swelling of lymph nodes
• Cervical area
• Typical “B” symptoms of lymphoma
• Unintentional weight loss
• ≥10% of body weight within previous six (6) months
• Fevers of >100.5°F (>38°C)
• ≥2 weeks w/o infection
• Drenching night sweat
• Without infection
• Extreme fatigue

Question 11

Physical findings of CLL

Answer 11

Physical Examination
• Lymphadenopathy most common abnormal finding
• Lymph node enlargement may be generalized or localize
• Cervical, supraclavicular & axillary sites
• Splenomegaly
• Leukemia cutis
• Macules, papules, plaques, nodules, ulcers, or blisters

Question 12

Lab findings in CLL

Answer 12

Laboratory
• Lymphocytosis
• As high as 100,000/microL (100 x 109/L)
• Blood smear
• Small, mature-appearing lymphocytes with darkly stained nucleus
• Partially condensed chromatin and indiscernible nucleoli.
• Neutropenia, anemia & thrombocytopenia
• Autoimmune hemolytic anemia (AIHA)

• Bone marrow aspirate & biopsy
• Not required for diagnosis of CLL
• Increased cellularity
• Lymphocytes >30% of all nucleated cells

Question 13

CLL diagnostics

Answer 13

Diagnostic Criteria
• Absolute B lymphocyte ≥5000/microL [5 x 109/L]
• At least three (3) months
• Predominate morphologically mature-appearing small lymphocytes
• Flow Cytometry
• Clonality of circulating B lymphocytes
• Confirmed by flow cytometry of peripheral blood
• Immunoglobulin light chain restriction (kappa or lambda)
• B cell associated antigens (CD19, CD20, CD23)
• T cell associated antigen (CD5)

Question 14

What is immune thrombocytopenia a need treatment

Answer 14

Immune Thrombocytopenia (ITP)
• Diagnosis of exclusion
• Bone marrow biopsy
• Normal/increased megakaryocytes
• Not always necessary
• Treatment
• Initiated platelet <20-30,000/μL
• Evidence of bleeding or invasive procedure
needs
• Platelet transfusion
• IVIG 1g/kg
• Glucocorticoids
• Methylprednisolone 1 g IV QD x3
doses

Question 15

What is autoimmune hemolytic anemia

Answer 15

• Autoimmune Hemolytic Anemia (AIHA)
• Diagnosis
• Coomb’s test
• Treatment
• Glucocorticoids
• IVIG with rituximab
• Blood transfusion

Question 16

CLL treatment

Answer 16

Current Recommendation
• Watchful waiting strategy
• Therapy reserved for symptomatic disease
• Symptoms Indicating Therapy
• Progressive marrow failure
• Progressive/symptomatic splenomegaly or lymphadenopathy
• Cytopenias not responding to therapy
• Continual constitutional symptoms
• Treatment Regimens for CLL
• Nucleoside analogues, alkylating agents & biologics
• Allogeneic stem cell transplantation
• Only known curative therapy
• Richter’s Transformation
• Combination of chemo & immunotherapy

Question 17

CLL complications

Answer 17

General Complications
• Infections, secondary cancers, autoimmune
& transformation
• Infection(s)
• A leading cause of disease related morbidity
• Immune dysfunction associated with
disease
• Risk for typical & atypical infections
• Secondary cancers
• Most common types: skin, prostate, &
breast cancers

utoimmune Complications
• Autoimmune cytopenias
• Autoimmune hemolytic anemia (AIHA)
• Antibody mediated destruction of RBC
• Isolated anemia
• Elevated retic count, bilirubin & LDH
• Low haptoglobin
• Check direct Coombs’s test
• Immune thrombocytopenia (ITP)
• Isolated thrombocytopenia
• Rapid decline in platelet levels
• AIHA + ITP = Evan’s syndrome
• Autoimmune complications of other organs
• Globular nephritis or vasculitis neuropathies
• Transformation Complication
• Richter’s transformation
• Aggressive lymphoma
• Rapid progression adenopathy, fatigue, night sweats, fever, weight loss

Question 18

What is Non Hodgkin’s lymphoma

Answer 18

Cancers of mature B, T & NK cells
• Tumors originate from lymphoid tissues
• Differ from Hodgkin’s lymphoma
• Lack of Reed-Sternberg cells
• Biologic & clinical characteristics
• Variable prognosis
Epidemiology
• In 2017 over 72,000 new cases of NHL in USA
• 8th & 9th most common cause of cancer related death in women
& men respectively
• Incidence ~10x compared Hodgkin’s lymphoma
• Higher incidence in Caucasians compared to African Americans
• Rises steadily with age
• After age of 40
• Common malignancies in adolescents/young adults

Question 19

Non-hodgkins lymphoma risk factors

Answer 19

Predisposition with primary & secondary immunodeficiency conditions
• HIV, transplant, autoimmune
• Environmental factors
• Agriculture chemical exposure
• Infectious agents
• EBV, HCV, H. pylori
• Chemical exposures & medical treatments
• Agricultural chemicals

Question 20

What are NHL mature T cell disorders

Answer 20

Distinguished based on specifics
• Clinical presentations, molecular or biologic features
• Significantly rarer
• Understanding less advanced
• Some can be cured with chemotherapy
• Majority associated with poor prognosis

Question 21

What is the cause, s/s, and prognosis of NK/T cell lymphomas

Answer 21

Etiology
• Associated with Epstein Barr virus (EBV) infection
• Epidemiology
• Most common in Asia & Peru native populations
• More common in men
• Median age ~60
• Clinical Presentation
• Obstructive symptoms in the upper digestive tract
• Prognosis
• Independent prognostic score
• Presence or absence of B symptoms
• Disease stage
• LDH elevation
• Lymph node involvement

Question 22

NHL s/s

Answer 22

Peripheral lymphadenopathy
• Firm and painless
• Present in more than 2/3 at presentation
• B-symptoms
• Fever – Persistent temperature >38°C (>100.4°F)
• Sweats – Drenching night sweats
• Weight loss – Unexplained loss over past six months
• Head & Neck
• Enlargement of preauricular nodes or tonsillar asymmetry
• Waldeyer’s ring
• Thoracic cavity
• Superior vena cava syndrome
• Pleural or pericardial effusions
• Abdomen and pelvis
• Retroperitoneal, mesenteric, and pelvic nodes is common
• Nodal enlargement do not produce symptoms or findings on physical examination
• Diffuse hepatosplenomegaly
• Extranodal sites
• Less than one-third have primary extranodal lymphoma
• Usually associated with aggressive NHLs
• Most common site is the gastrointestinal tract followed by skin
• Other sites involved include: testis, bone, and CNS

Question 23

NHL diagnostics

Answer 23

aboratory Studies
• CBC, CMP, LDH
• Screen for HIV, HBV, HCV
• Imaging
• Identifies sites of lymph node or organ involvement
• Aids in selection of site for diagnostic biopsy
• Lymphoma histology & clinical presentation dictates imaging studies
• Chest/abdomen/pelvic computed tomography (CT) scans
• Assessment of adenopathy for indolent lymphomas
• Positron Emission Tomography (PET) scan
• Aggressive lymphomas
• Magnetic Resonance Imaging (MRI)
• Detecting bone, bone marrow & CNS disease
• Biopsy
• Required for diagnosis & classification
• Obtained urgently if suspecting aggressive NHL
• Staging of certain diseases
• Involve bone marrow biopsy
• Lumbar puncture
• If concerned for CNS involvement
• Ann Arbor staging system
• Treatment Plan
• Driven by subtype

Question 24

What is Hodgkin’s lymphoma

Answer 24

Hodgkin’s lymphomas (HL)
• Lymphoid neoplasms
• Malignant Hodgkin/Reed-Sternberg (HRS)
• Divided into two (2) major categories
• Classic HL (cHL) (90%)
• Nodular sclerosis cHL (NSCHL)
• Mixed cellularity cHL (MCCHL)
• Lymphocyte rich cHL (LRCHL)
• Lymphocyte depleted cHL (LDCHL)
• Nodular lymphocyte predominant HL (NLPHL)

Question 25

What are symptoms of Hodgkin’s lymphoma

Answer 25

Slow progression
• Variable tempo of disease
• Lymphadenopathy
• Neck most common site of involvement
• Cervical and/or supraclavicular nodes
• Enlarged axillary nodes
• Inguinal
• Mediastinal nodes
• Retroperitoneal nodes
• Infradiaphragmatic lymphadenopathy alone is uncommon
• Constitutional & B-symptoms
• Fatigue, and/or pruritus
• Fever, weight loss, night sweats
• Mediastinal masses
• Large before causing chest discomfort or respiratory symptoms
• Discovery of mediastinal mass on routine CXR is common presentation
• Mass may be associated with symptoms

Question 26

Diagnostics of Hodgkin’s lymphoma

Answer 26

Laboratory
• CBC, ESR, BMP, LFTs, albumin
• Imaging
• Potential sites for biopsy
• Evaluation of organ involvement
• Diagnosis
• Suspect with lymphadenopathy or mediastinal mass w/wo B-symptoms
• Diagnosis requirements
• Immunophenotype of Hodgkin/Reed-Sternberg (HRS) cells
• Tissue biopsy
• Different modalities
• Dependent on location
• Excisional or incisional biopsy of a peripheral lymph node
• CT guided
• Surgical approach
• Determines histologic type
• Fine needle aspiration (FNA) does not provide sufficient tissue

Question 27

Treatment plan for Hodgkin’s lymphoma early vs late stage

Answer 27

Majority of patients will be cured
• Chemotherapy alone
• Combination chemotherapy & radiation therapy
• Early Stage
• Most common chemotherapy regimen
• ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine)
• 4-6 week cycle
• Unfavorable risk of disease
• Radiation therapy added
• Late Stage
• Advanced stage of disease do not benefit from addition of radiation therapy
• ABVD for 6-week cycle