Leukemia, Lymphoma, & Multiple Myeloma Flashcards
Abnormally low neutrophils is called:
Neutropenia
Reduction in mature blood cells is called:
Cytopenia
Pancytopenia is a deficiency of:
All three cellular components (RBCs, WBCs, Platelets)
Normal WBC count
4,400-11,000/mcL
< 4.5K WBC
Leukopenia
WBC >10K
LEUKOCYTOSIS
_________ is cancer of the body’s blood forming tissues
Leukemia
Effects Bone Marrow and Lymphatic System
High numbers of WBCs
• Immature cells
•Fast growth
Types: • Acute Myeloid Leukemia (AML) • Chronic Myeloid Leukemia (CML) • Acute lymphoblastic Leukemia (ALL) • Chronic lymphocytic Leukemia (CLL)
Most common acute leukemia in adults is:
Acute Myeloid Leukemia (AML)
Relatively rate even though most common leukemia
Median age ~65 years Incidence increases with: • Age • M:F ratio ~5:3 • Caucasians
Acute Myeloid Leukemia is characterized by an accumulation of ________________.
Leukemia blasts
Peripheral blood is ALWAYS abnormal —> biopsy
Reduced production of normal cells (neutrophils, erythrocytes, platelets)
AML Associations
Environmental Factors:
***Chemical exposure, radiation, tobacco, chemotherapy
Genetic abnormalities:
Trisomy 21, Fanconi’s anemia, Familial RUNX1 mutations
Malignant hematologists diseases
***Myelodysplastic syndrome (MDS), Myeloproliferative disorders
Clinical presentation of AML
ANEMIA:
• shortness of breath
• dyspnea on exertion
• weakness/fatigue
NEUTROPENIA:
• Infection and fever related to infection
THROMBOCYTOPENIA:
• Bleeding (conjunctival hemorrhages, gingival bleeding, epistaxis, petechiae, menorrhagia, ecchymosis)
OPHTHALMIC CHANGES
• Hemorrhages or white plaques
AML Diagnostic tests
***Bone marrow aspiration and biopsy
Blasts form ≥20% of cellularity
<20% blasts in BM with cytogenetic abnormalities
CBC with diff —> cytopenia and blasts ≥ 20%
AUER RODS on peripheral smear
Elevated Creatinine and LFTs and altered electrolytes
Elevated Uric Acid and Lactate Dehydrogenase (LDH) (both from high cell turnover)
Absolute Neutrophil Count (ANC)
Normal = 2500-7500 (calculated as WBC x % neutrophils)
Neutrophilia (>10K) could be reactive (stress, trauma), proliferation (cancer), demargination (stress, infection), from meds (corticosteroids), from poison
Neutropenia could be from chemo, radiation, blood CA, overwhelming infection or meds (PCN)
If ANC is abnormal, RECHECK
What are AUER RODS?
Clumps of azurophilic granule material
Form elongated needles in leukemia blasts
**Pathognomonic of myeoblasts —> AML
AML treatment
Induction = chemotherapy (heavy), with goal to eradicate most leukemic cells
Consolidation = stem cell transplant, with goal to destroy remaining leukemic cells
Maintenance = lower dose chemo, supportive measures
Targeted therapies for certain mutations
AML prognosis
Favorable if: • < 60 years old • Good performance status • No comorbities (ie DM, CAD) • No Hx of exposures to cytotoxic agents or radiation
Unfavorable if:
• Age > 60
• Hx of exposure
• Hx of myelodysplasia
Myelodysplastic Syndrome (MDS)
Cytopenia (low # blood cells) Ineffective hematopoiesis May be asymptomatic More common in those >60 (increased incidence in men, smokers, benzene exposure) May progress to AML
Can be treatment related (chemotherapy, radiation therapy)
• Peak incidence 4-6 years after treatment
MDS Treatment
Hematopoietic growth factors help blood cells grow/mature
Immunomodulatory agents can alter or regulate immune function
Hypomethylating agents inhibit DNA methylation
Immunosuppressive therapy
Goals to Tx: Minimize cytopenias, maintain quality of life, delay onset of AML transformation
Tumor Lysis Syndrome
ONCOLOGIC EMERGENCY! Associated with high mortality
Massive tumor cell lysis —> release of cell contents (Potassium, phosphate, nucleic acids)
Causes:
• Initiation of cytotoxic therapy (usually within 12-24 hours of start of chemo) - possible at at treatment but esp. at first
• Spontaneously with some tumor types (high proliferation rate, large tumor burden, high sensitivity to cytotoxic therapy)
The four blood manifestations of tumor lysis syndrome:
Hyperkalemia (inc. potassium)
Hyperphosphatemia (inc. phosphate)
Hypocalcemia (dec. calcium)
Hyperuricemia (inc uric acid)
Tumor Lysis Syndrome may result in …
Renal failure —> hemodialysis
ECG changes (arrhythmia)
Seizure
Tetany
Treatment of Tumor Lysis Syndrome
PREVENTION! Fluids, dieresis Frequent monitoring during therapy (Creatinine, Potassium, Phosphorus, Uric Acid, Calcium) Meds to lower Uric Acid Monitor cardiac function Seizure precautions Treat hyperkalemia and hyperphosphatemia Preserve renal function (dialysis)
Chronic Myeloid Leukemia
AKA Chronic Myelogenous Leukemia
Uncontrolled production of mature and maturing granulocytes (neutophils and some basophils, eosinophils)
Abnormal gene called BCR-ABL1 fusion gene resulting from the translocation of chromosomes 9 & 22 (Philadelphia Chromosome)
15-20% of leukemia’s in adults (rare)
Slight male predominance
Median age at presentation ~50 years
Risk factor: Ionizing radiation
CML signs and symptoms
20-50% are asymptomatic (first suspected on routine blood tests - WBC > 100K, Platelets >600K)
Fatigue (34%) Malaise (3%) Abdominal fullness (15%) *Splenomegaly (48-76%) Bleeding episodes (21%) Pain over lower sternum (expanding bone marrow) B symptoms • Fever • Weight loss 20% • Drenching night sweats 15%
The three phases of CML are:
Chronic
• 85% of pats diagnosed here (often asymptomatic)
• LEUKOCYTOSIS WBC >100K
• <10% blood or BM blast cells
• Chance for remission is high if to started in this phase
Accelerated
• 10-19% blood or BM cells are blasts
• Progressively impaired neutrophil diff
• Leukocyte counts more difficult to control
• Sx - Anemia, fatigue, malaise, flu-like Sx
Blast Crisis
• Resembles acute leukemia
• 20% or more of blood or BM cells are blasts
• Sx - fatigue, fever, extramedullary blasts, splenomegaly
Diagnosis of CML
Confirmed by identification of Philadelphia chromosome and/or BCR-ABL
Treatment for CML depends on _________
Stage at Dx
Tyrosine Kinase Inhibitors - reduces cell communication and reproduction
Monoclonal Antibodies - Flag CA cells, trigger cell membrane destruction, block cell growth, prevent blood vessel growth, block immune system inhibitors, deliver chemo/radiation
Allogenic Stem Cell Transplant (possible cure)
Prognosis depends on phase as presentation (chronic phases = years of control, accelerated/blastic = poor prognosis), response to TKI tx, and age>65
Complications for CML
Tumor lysis syndrome
HYPERLEUKOCYTOSIS - WBC >100K
• Medical emergency
• Decreased tissue perfusion, may require leukapheresis
Hyperviscosity syndrome - spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, neuro symptoms, headache, vertigo, seizures, coma
• Treat with leukapheresis (blood filter) or plasma exchange
The most common cancer in children and teens?
Acute Lymphoblastic Leukemia (ALL)
About 30% of all childhood CA
Peak incidence at 2-5 years of age
M>F
Caucasians + Hispanics > African Americans
Cure rate more favorable in children
Clinical features of ALL
- Fever
- Fatigue
- Pallor
- Hepatosplenomegaly (64/61%)
- Lymphadenopathy (50%)
Other Sx: Lethargy, petechiae/ecchymosis, bone pain
Thymic mass (superior vena cava syndrome, superior mediastinal syndrome)
Testicular mass (rare, painless, unilateral)
Children: Limp, arthralgia, bleeding
Elderly: Anemia-associated dyspnea, angina, dizziness
Lab findings for ALL
Lymphoblasts on peripheral blood smear
Cytopenias (neutropenia, anemia, thrombocytopenia)
Elevated LDH
Dx:
• BM biopsy
Bone marrow biopsy findings for ALL
Morphology (shape)
Immunophenotype (proteins expressed by cells)
• 70-80% B precursor
• 15-17% T precursor
Cytogenics (chromosomal abnormalities)
Different types of ALL
Precursor B-cell ALL
• 70-80% of all childhood cases
• 80% express CD10
• Favorable prognosis
T-cell ALL • Standard relapse risk • Male predominance • Medistinal Mass • Intramedullary disease
Mature B-cell ALL • Also called Burkitt cell leukemia/lymphoma • Male predominance • Bulky extramedullary disease • Often presents with CNS symptoms
ALL treatment
Chemotherapy
Induction
• Goal to reduce tumor burden by 99%
• Restore normal hematopoiesis
• Mortality 5%
Consolidation
Maintenance
Children have 98% rate of complete response
ALL Prognosis
Good —> 5-year survival >85% if: • Age at Dx <35 • Favorable cytogenetic • Absence of CNS disease at Dx • B-cell v T-cell phenotype
Poor for all others
Chronic lymphocytic leukemia (CLL) is characterized by progressive _____________________________________.
Accumulation of functionally incompetent B-cell lymphocytes
Most prevalent leukemia in western countries
35% of leukemia in US - adults only
Median age at dx is 70
M:F is 2:1, caucasians most affected
Clinical Features of CLL
Bone Marrow failure —> anemia, thrombocytopenia, neutropenia
Organomegaly - most common finding at Dx (LAD 50-90%, Spleen 25-55%, Liver 15-25%)
Skin is the most common non-lymphoid organ affected (Leukemia cutis)
CLL Indolent Stage
Most patients are asymptomatic
Lymphocytosis on blood work
B symptoms
• Unintentional weight loss ≥10% in 6 months
• Fevers >100.5 for at least 2 weeks with no infections
• Drenching night sweats
• Extreme fatigue
Advanced Stage CLL
Rapidly progressive/terminal phase May follow indolent phase Lasts 1-2 years Anemia B symptoms Atypical infections Death secondary to infection, bleeding, cachexia
CLL Diagnostic Tests
CBC w Diff • Absolute B lymphocytes ≥5000µL • Mature appearing, small lymphocytes Flow cytomegalovirus of peripheral blood • Clonality of B lymphocytes Bone Marrow Aspirate and biopsy • Increased cellularity • Lymphocytes > 30% Lymph node biopsy • Infiltrate-mostly mature appearing, small lymphocytes
CLL Prognosis
Based on Staging (Rai and Binet systems)
• Asymptomatic early stage, median survival >10 years
• Advanced stage or progressive disease, 18 mon to 3 years survival rate without treatment
Lymphocyte doubling time
• <12 months = significantly shorter survival rate
CLL Treatment
Asymptomatic early stage
• Observation - not all pt require Tx
• Localized radiation therapy
Chemotherapy
Immunotherapy
• Rituximab (CD20) and other monoclonal antibodies, used in combo with chemo
Radiation
Splenectomy
Lymphoma is defined as cancer that begins in ______________
The lymphocytes
Lymphocytes located in lymph nodes, spleen, thymus, bone marrow, tonsils, adenoids
Main types = Hodgkin and Non-Hodgkin
Risk factors for Hodgkin Lymphoma
Socioeconomic status Hx of mono caused by EBV Immunosuppressive Autoimmune disorders Family Hx
Characteristics of Hodgkin Lymphoma
Enlargement of lymph nodes, spleen, liver
REED-STERNBERG CELLS - Multinucleated B Cell
• Aka “Popcorn cells”
Virus found in the Hx for 40-50% of Hodgkin Lymphoma cases
Epstein Barr Virus
Key Clinical Features of HL
Painless LAD - cervical most common presentation
Mediastinal mass (incidental finding on CXR)
Severe pain response after alcohol
Systemic symptoms (B symptoms)
• Fever > 100.4
• Night sweats
• Weight loss
Fatigue
Pruritus without rash
What are the B symptoms?
Weight loss
Fever
Night sweats
Hodgkin Lymphoma diagnostics
Lymph node biopsy —> Reed Sternberg cells confirm Dx
Staging involves CT/PET of neck, chest, abdomen, pelvis
Treatment of Hodgkin Lymphoma
Combination chemotherapy curative in most cases (even end-stage)
Often combined with radiation Tx (particularly in bulky disease or relapsed disease)
Stem Cell Transport - secondary relapse or persistent progressive disease
Prognosis for HL
Curable in >75% of patients
Worse prognosis for those with:
• Affected lymph nodes on both sides of the diaphragm
• Bulky disease
• Distant spread
Other considerations for Hodgkin Lymphomas
Secondary malignancy or recurrence of HL CAD Pulmonary dysfunction Infertility Hypothyroidism DM Psychosocial issues
Non-Hodgkin Lymphoma
Can be derived from B or T cells (90% are derived from B lymphocytes)
Risk Factors:
• Personal or familial Hx of lymphoma
• Exposure to pesticides, hair dyes
Associations:
• Immunodeficiency *HIV)
• Autoimmune disease (Lupus, RA, Sjogren’s, Hashimoto’s)
• Inflammatory GI disease (Crohn’s, H pylori)
Clinical Features of NonHodgkin Lymphoma
Painless, persistent LAD (diffuse or isolated)
Mediastinal mass in 20%
Extra lymphatic sites (GI, skin, bone, BM, abdominal fullness)
B symptoms in intermediate/high grade
Aggressive NonHod Lymphomas
1/3 curable with chemo
Rapidly growing mass - mediastinal or GI
B Symptoms
Elevated LDH/uric acid
Diagnostic studies for NHL
Biopsy for diagnosis/classification
• lymph nodes 2cm or > give best Dx
CT or PET/CT to learn areas of involvement and preferred biopsy site
Bone marrow aspiration and biopsy
Other options • CSF LP • Pleural fluid • Peritoneal fluid • Splenectomy
Lugano classification for lymphomas
I - one node or a group of adjacent nodes
II - two or more nodal groups on the same side of diaphragm
II bulky - II with bulky disease
III - Nodes on both sides of diaphragm and with spleen involvement
IV - additional noncontiguous extralymphatic involvement
NHL treatment
Based on stage of disease and patients clinical status
Indolent with 1-2 nodes = Radiation alone
Agressive intermediate or high grade —> Chemo, immunotherapy, autologous stem cell transplant
General characteristics of Multiple Myeloma
Malignancy of plasma cells, proliferating in BM • Extensive skeletal destruction • Osteolytic lesions • Osteopenia • Pathologically fractures
Can form tumors —> spinal compression
Instead of making immunoglobulins, plasma cells secrete paraproteins
• Paraproteins in blood —> hyperviscosity
• Paraproteins in urine —> renal failure
Protein electrophoresis
Performed on blood/urine to show paraproteins as varying narrow bands on the test strip
Demonstrates which paraproteins is present
Provides an early indication of malignant condition
Multiple Myeloma —> “M spike”
Clinical Presentation of Multiple Myeloma
Fatigue (32%) Back pain Neurological changes (weakness in 32%, paresthesia of LE, bladder/bowel incontinence) Bone pain (58%) esp low back, ribs Infections Renal Failure Bleeding Weight loss (24%)
Hyperviscosity Syndrome
Spontaneous bleeding from mucous membranes
Visual disturbances due to retinopathy
Neurological symptoms (HA, vertigo, seizures, coma)
Diagnostic studies for Multiple Myeloma
CRAB • Calcium > 10.5 • Renal Insufficiency (Cre >2) • Anemia (Hb <10) • Bone Lesions
ROULEAUX formation (RBC stacks)
Hallmark: MONOCLONAL SPIKE on Protein electrophoresis (SPEP or UPEP) “M Spike”
BENCE-JONES proteins in urine
X-rays of axial skeleton —> lytic lesions, general osteoporiosis
Treatment for Multiple Myeloma
Refer to hematology/oncology
Combo chemotherapy
Vertebroplasty or balloon kyphoplasty
IV BISPHOSPHONATES prevent the loss of bone mass
Autologous Hemopoeitic Cell Transplant (HCT)
